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Clinical Trial Results:
A randomized, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and effects on heterotopic bone formation of REGN2477 in patients with Fibrodysplasia Ossificans Progressiva

Summary
EudraCT number	2016-005035-33
Trial protocol	GB NL IT ES
Global end of trial date	16 Sep 2021

Results information
Results version number	v1(current)
This version publication date	11 Oct 2022
First version publication date	11 Oct 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

R2477-FOP-1623

ISRCTN number

US NCT number

NCT03188666

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron Pharmaceuticals, Inc

Sponsor organisation address

777 Old Saw Mill River Rd., Tarrytown, NY, United States, 10591

Public contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc, 001 8447346643, clinicaltrials@regeneron.com

Scientific contact

Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc, 001 8447346643, clinicaltrials@regeneron.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 Sep 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Sep 2021

Was the trial ended prematurely?

Main objective of the trial

The primary safety objective of the study is to assess the safety and tolerability of REGN2477 in male and female subjects with fibrodysplasia ossificans progressiva (FOP). The primary efficacy objective of the study is to assess the effect of REGN2477 versus placebo on the change from baseline in heterotopic ossification (HO) in subjects with FOP, as determined by 18-NaF uptake in HO lesions by positron emission tomography (PET) and in total volume of HO lesions by computed tomography (CT).

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonization (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Feb 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 10

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Spain: 2

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Italy: 9

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

United States: 8

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 48 participants were screened, out of which, 44 participants were randomized and treated.

Screening details

This three-period study consisted of a 28 week, randomized, double-blind placebo-controlled treatment period (Period 1) followed by 28 weeks, open-label treatment (Period 2) and 20-weeks follow-up treatment (Period 3). Participants could continue receiving REGN2477 every 4 weeks beyond week 76 provided that no safety signals were identified.

Period 1 title

Period 1 (28 weeks double-blind)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received a single dose of placebo matched to REGN2477 intravenous (IV) infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received placebo matched to REGN2477 IV infusion Q4W in period 1

REGN2477 10 mg/kg Q4W

Arm description

Participants received a single dose of REGN2477 10 milligrams per kilogram (mg/kg) IV infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Arm type

Experimental

Investigational medicinal product name

REGN2477

Investigational medicinal product code

Other name

garetosmab

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received REGN2477 10 mg/kg IV infusion Q4W

Number of subjects in period 1	Placebo	REGN2477 10 mg/kg Q4W
Started	24	20
Completed	24	19
Not completed	0	1
Adverse event, non-fatal	-	1

Period 2 title

Period 2 (28 weeks open-label)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/REGN2477 10 mg/kg Q4W

Arm description

Participants who were in the placebo group in Period 1 crossed over to receive a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2.

Arm type

Experimental

Investigational medicinal product name

REGN2477

Investigational medicinal product code

Other name

garetosmab

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received REGN2477 10 mg/kg IV infusion Q4W in Period 2

REGN2477/REGN2477 10 mg/kg Q4W

Arm description

Participants who were in the REGN2477 group in Period 1 continued treatment with a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2.

Arm type

Experimental

Investigational medicinal product name

REGN2477

Investigational medicinal product code

Other name

garetosmab

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received REGN2477 10 mg/kg IV infusion Q4W in Period 2

Number of subjects in period 2	Placebo/REGN2477 10 mg/kg Q4W	REGN2477/REGN2477 10 mg/kg Q4W
Started	24	19
Completed	24	18
Not completed	0	1
Adverse event, serious fatal	-	1

Period 3 title

Period 3 and beyond to EOS

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/REGN2477 10 mg/kg Q4W

Arm description

Participants who were in the placebo group in Period 1 crossed over and received Q4W IV infusions of REGN2477 for additional 28 weeks during Period 2 followed by 20 weeks during Period 3. Participants could continue receiving REGN2477 every 4 weeks beyond week 76 provided that no safety signals were identified. *Note: One death was reported for a participant that continued receiving REGN2477 beyond week 76. See Adverse Events section for Total # of Deaths (all causes).

Arm type

Experimental

Investigational medicinal product name

REGN2477

Investigational medicinal product code

Other name

garetosmab

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received REGN2477 10 mg/kg IV infusion Q4W in Period 3

REGN2477/REGN2477 10 mg/kg Q4W

Arm description

Participants who were in the REGN2477 group in Period 1 continued treatment with a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2 followed by 20 weeks during Period 3. Participants could continue receiving REGN2477 every 4 weeks beyond week 76 provided that no safety signals were identified.

Arm type

Experimental

Investigational medicinal product name

REGN2477

Investigational medicinal product code

Other name

garetosmab

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received REGN2477 10 mg/kg IV infusion Q4W in Period 3

Number of subjects in period 3	Placebo/REGN2477 10 mg/kg Q4W	REGN2477/REGN2477 10 mg/kg Q4W
Started	24	18
Completed week 76	21	16
Completed	20	16
Not completed	4	2
Adverse event, serious fatal	1	2
Consent withdrawn by subject	2	-
AE, serious fatal (occurred after week 76)*	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received a single dose of placebo matched to REGN2477 intravenous (IV) infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Reporting group title

REGN2477 10 mg/kg Q4W

Reporting group description

Participants received a single dose of REGN2477 10 milligrams per kilogram (mg/kg) IV infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Reporting group values	Placebo	REGN2477 10 mg/kg Q4W	Total
Number of subjects	24	20	44
Age categorical
Units: Subjects
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	24	20	44
From 65-84 years	0	0	0
85 years and over	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	27.8 ( 8.54 )	27.3 ( 8.67 )	-
Sex: Female, Male
Units: Participants
Female	14	11	25
Male	10	9	19
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0
Not Hispanic or Latino	24	20	44
Unknown or Not Reported	0	0	0
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	1	2	3
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	0	1
White	22	17	39
More than one race	0	0	0
Unknown or Not Reported	0	1	1
Fibrodysplasia Ossificans Progressiva (FOP) Genetic Mutation
Units: Subjects
Active HO classic ACVR1 (R206H)	22	20	42
Other	2	0	2
Total Lesion Activity (TLA) at Baseline as Assessed by 18 F-NaF PET (AHO)
Fluorine-18 sodium fluoride 18^F-NaF PET is used to assess lesion and disease activity. The baseline-Active Heterotopic ossification (AHO) analysis set included all randomized participants who had at least one active HO lesion at baseline; it is based on the treatment allocated (as randomized).
Units: g.
arithmetic mean (standard deviation)	473.40 ( 348.373 )	418.18 ( 372.801 )	-
Total Volume of HO Lesions at Baseline as Assessed by Computed Tomography (CT) (AHO)
The baseline-Active Heterotopic ossification (AHO) analysis set includes all randomized participants who had at least one active HO lesion at baseline; it is based on the treatment allocated (as randomized).
Units: cubic centimeter (cm^3)
arithmetic mean (standard deviation)	235.78 ( 253.329 )	251.43 ( 327.881 )	-
Total Lesion Activity at Baseline as Assessed by 18F-NaF PET (AHOC)
The baseline-active HO classic ACVR1 [R206H] mutation analysis set (AHOC) includes all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one active HO lesion(s) at baseline, as defined by 18F-NaF PET positivity; it is based on the treatment allocated (as randomized).
Units: g.
arithmetic mean (standard deviation)	464.27 ( 350.479 )	418.18 ( 372.801 )	-
Total Volume of HO Lesions at Baseline as Assessed by CT (AHOC)
The baseline-active HO classic ACVR1 [R206H] mutation analysis set (AHOC) includes all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one active HO lesion(s) at baseline, as defined by 18F-NaF PET positivity; it is based on the treatment allocated (as randomized).
Units: cubic centimeter (cm^3)
arithmetic mean (standard deviation)	239.72 ( 263.813 )	251.43 ( 327.881 )	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received a single dose of placebo matched to REGN2477 intravenous (IV) infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Reporting group title

REGN2477 10 mg/kg Q4W

Reporting group description

Participants received a single dose of REGN2477 10 milligrams per kilogram (mg/kg) IV infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Reporting group title

Placebo/REGN2477 10 mg/kg Q4W

Reporting group description

Participants who were in the placebo group in Period 1 crossed over to receive a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2.

Reporting group title

REGN2477/REGN2477 10 mg/kg Q4W

Reporting group description

Participants who were in the REGN2477 group in Period 1 continued treatment with a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2.

Reporting group title

Placebo/REGN2477 10 mg/kg Q4W

Reporting group description

Reporting group title

REGN2477/REGN2477 10 mg/kg Q4W

Reporting group description

Subject analysis set title

Placebo/REGN2477 10 mg/kg Q4W (SAF)

Subject analysis set type

Safety analysis

Subject analysis set description

The safety analysis set (SAF) included all randomized participants who received any study drug and were analyzed as treated.

Subject analysis set title

REGN2477/REGN2477 10 mg/kg Q4W (SAF)

Subject analysis set type

Safety analysis

Subject analysis set description

The SAF included all randomized participants who received any study drug and were analyzed as treated.

Subject analysis set title

Period 1: Placebo (AHO)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The active heterotopic ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized). Participants received a single dose of placebo matched to REGN2477 IV infusion Q4W for up to 28 weeks during Period 1.

Subject analysis set title

Period 1: REGN2477 10 mg/kg Q4W (AHO)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The AHO analysis set included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized). Participants received a single dose of REGN2477 10 mg/kg IV infusion Q4W for up to 28 weeks during Period 1.

Subject analysis set title

Period 1: Placebo (AHOC)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The active HO classic ACVR1 (R206H) mutation analysis set (AHOC) included all randomized participants with the classic ACVR1 (R206H) mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized). Participants received a single dose of placebo matched to REGN2477 IV infusion Q4W for up to 28 weeks during Period 1.

Subject analysis set title

Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The AHOC analysis set included all randomized participants with the classic ACVR1 (R206H) mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized). Participants received a single dose of REGN2477 10 mg/kg IV infusion Q4W for up to 28 weeks during Period 1.

Subject analysis set title

Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The COVID-19 modified intent-to-treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan. Participants who were in the placebo group in Period 1 crossed over to receive a single dose of REGN2477 IV infusion Q4W for additional 28 weeks (up to Week 56) during Period 2.

Subject analysis set title

Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The COVID-19 mITT included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan. Participants who were in the REGN2477 group in Period 1 continued treatment with a single dose of REGN2477 IV infusion Q4W for additional 28 weeks (up to Week 56) during Period 2.

Subject analysis set title

REGN2477 10 mg/kg Q4W (PK)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The pharmacokinetic (PK) analysis set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration following the first dose of study drug. Concentrations were merged from both treatment groups, REGN2477/REGN2477 and placebo/REGN2477, by nominal time after active REGN2477 treatment. The pre-dose for treatment group placebo/REGN2477 was Week 28 before active dosing sample.

Subject analysis set title

Placebo/REGN2477 10 mg/kg Q4W (ADA)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The anti-drug antibody (ADA) analysis set included all treated patients who received any amount of study drug (active or placebo [safety analysis set]) and had at least one non-missing anti-REGN2477 antibody result following the first dose of study drug or placebo. The ADA analysis set was based on the actual treatment received (as treated) rather than as randomized.

Subject analysis set title

REGN2477/REGN2477 10 mg/kg Q4W (ADA)

Subject analysis set type

Sub-group analysis

Subject analysis set description

The ADA analysis set included all treated participants who received any amount of study drug (active or placebo [safety analysis set]) and had at least one non-missing anti-REGN2477 antibody result following the first dose of study drug or placebo. The ADA analysis set was based on the actual treatment received (as treated) rather than as randomized.

Primary: Period 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

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End point title

Period 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs ^[1]

End point description

Treatment-emergent adverse events are adverse events not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious TEAE was defined as any untoward medical occurrence that resulted in any of following outcomes not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. Number of participants with TEAEs and Serious TEAEs are reported. Safety analysis set (SAF) included all randomized participants who received any study drug and were analyzed as treated.

End point type

Primary

End point timeframe

Up to Week 28

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data were planned to be analyzed.

End point values	Placebo	REGN2477 10 mg/kg Q4W
Number of subjects analysed	24	20
Units: Participants
Participants with at least one TEAE	24	20
Participants with at least one serious TEAE	2	4

No statistical analyses for this end point

Primary: Period 1: Number of Participants with TEAEs by Severity

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End point title

Period 1: Number of Participants with TEAEs by Severity ^[2]

End point description

Severity of TEAEs were graded as follows: Mild: Does not interfere in a significant manner with the participant’s normal functioning level. It may be an annoyance. Prescription drugs are not ordinarily needed for relief of symptoms but may be given because of personality of the participants. Moderate: Produces some impairment of functioning but is not hazardous to health. It was uncomfortable or an embarrassment. Treatment for symptom may be needed. Severe: Produces significant impairment of functioning or incapacitation and was a definite hazard to the participant’s health. Treatment for symptom may be given and/or participants hospitalized. Number of participants with TEAEs by severity is reported. Safety analysis set (SAF) included all randomized participants who received any study drug and was analyzed as treated.

End point type

Primary

End point timeframe

Up to Week 28

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data were planned to be analyzed.

End point values	Placebo	REGN2477 10 mg/kg Q4W
Number of subjects analysed	24	20
Units: Participants
Participants with at least one Mild TEAE	9	7
Participants with at least one Moderate TEAE	12	10
Participants with at least one Severe TEAE	3	3

No statistical analyses for this end point

Primary: Period 1: Time-Weighted Average (Standardized Area Under the Curve [AUC]) of the Percent Change From Baseline in Total Lesion Activity by Fluorine-18-labeled Sodium Fluoride (18^F-NaF) Positron Emission Tomography (PET) over 28 weeks (AHO)

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End point title

Period 1: Time-Weighted Average (Standardized Area Under the Curve [AUC]) of the Percent Change From Baseline in Total Lesion Activity by Fluorine-18-labeled Sodium Fluoride (18^F-NaF) Positron Emission Tomography (PET) over 28 weeks (AHO)

End point description

18^F-NaF PET is used to assess lesion and disease activity. Time-weighted average (standardized area under the curve [AUC]) of the percent change from baseline in total lesion activity by 18^F-NaF PET over 28 weeks in AHO analysis set is reported. Active Heterotopic Ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized).

End point type

Primary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	24	20
Units: Percent Change
least squares mean (standard error)	13.7 ( 12.49 )	-11.1 ( 14.28 )

LS Mean Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0758 ^[3]

Method

Mixed models analysis

Parameter type

Least Square Mean Difference

Point estimate

-24.8

Confidence interval

level

95%

sides

2-sided

lower limit

-52.3

upper limit

2.7

Notes
[3] - p-Value vs. Placebo; Mixed Model Repeated Measures

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by Computed Tomography (CT) at Week 28 (AHO)

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End point title

Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by Computed Tomography (CT) at Week 28 (AHO)

End point description

CT is a diagnostic imaging test used to create detailed images of internal organs, bones, soft tissue and blood vessels. Percent change from baseline in the total volume of HO lesions as assessed by CT during Period 1 at Week 28 is reported. AHO included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized).

End point type

Primary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	24	20
Units: Percent Change
least squares mean (standard error)	30.7 ( 19.30 )	5.5 ( 21.28 )

LS Mean Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3676 ^[4]

Method

Mixed models analysis

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-25.2

Confidence interval

level

95%

sides

2-sided

lower limit

-81.1

upper limit

30.6

Notes
[4] - p-Value vs. Placebo; Mixed Model Repeated Measures (MMRM)

Primary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[5]

End point description

HO detectable by CT that developed after baseline are referred to as “new HO lesions." Number of new HO lesions as assessed by CT at Week 56 relative to Week 28 scan is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT): All AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses is less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Primary

End point timeframe

Week 28, Week 56

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: New HO Lesions
New lesions	22	0

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared number of new lesions per participant by CT at week 28 (relative to baseline) and week 56 (relative to week 28).

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039 ^[6]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[6] - Week 56 vs. Week 28

Primary: Period 1: Time-weighted Average (Standardized AUC) of the Percent Change From Baseline in Total Lesion Activity Assessed by 18^F-NaF PET over 28 weeks (AHOC)

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End point title

Period 1: Time-weighted Average (Standardized AUC) of the Percent Change From Baseline in Total Lesion Activity Assessed by 18^F-NaF PET over 28 weeks (AHOC)

End point description

18^F-NaF PET is used to assess lesion and disease activity. Time-weighted average (Standardized AUC) of the percent change from baseline in total lesion activity as assessed by 18^F-NaF PET in Active HO Classic ACVR1 Mutation (AHOC) analysis set over 28 weeks is reported. Active HO classic ACVR1 (R206H) mutation analysis set (AHOC) included all randomized participants with the classic ACVR1 (R206H) mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Primary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	22	20
Units: Percent Change
least squares mean (standard error)	17.6 ( 9.73 )	-8.0 ( 10.14 )

REGN2477 10 mg/kg Q4W vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0756

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-25.6

Confidence interval

level

95%

sides

2-sided

lower limit

-53.9

upper limit

2.8

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by CT at Week 28 (AHOC)

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End point title

Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by CT at Week 28 (AHOC)

End point description

Percent change from baseline in the total volume of HO lesions was assessed by CT at Week 28 in AHOC analysis set is reported. Active HO classic ACVR1 (R206H) mutation analysis set (AHOC) included all randomized participants with the classic ACVR1 (R206H) mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Primary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	22	20
Units: Percent Change
least squares mean (standard error)	34.9 ( 19.90 )	7.0 ( 20.87 )

REGN2477 10 mg/kg Q4W vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3407

Method

Mixed Model with Repeated Measure (MMRM)

Parameter type

Least Square Mean Difference

Point estimate

-27.8

Confidence interval

level

95%

sides

2-sided

lower limit

-86.1

upper limit

30.5

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to Fibrodysplasia Ossificans Progressiva (FOP) Assessed by Daily Numeric Rating Scale (NRS) over 28 weeks (AHO)

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End point title

Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to Fibrodysplasia Ossificans Progressiva (FOP) Assessed by Daily Numeric Rating Scale (NRS) over 28 weeks (AHO)

End point description

The pain NRS is a patient reported outcome (PRO) used by participants to rate their pain associated with FOP. Participants were asked to rate their pain on a scale that ranges from “0” (no pain) to “10” (worst possible pain), where the highest score indicated worst outcome. Time-weighted average (Standardized AUC) of the change from baseline in daily pain due to FOP assessed by daily NRS over 28 weeks in AHO analysis set is reported. Active Heterotopic Ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized). "Number of participants analyzed” are the participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	23	18
Units: Score on a Scale
least squares mean (standard error)	-0.27 ( 0.373 )	-0.63 ( 0.444 )

LS Mean Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2546 ^[7]

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-1.01

upper limit

0.27

Notes
[7] - p-Value vs. Placebo

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to FOP, Assessed by Daily NRS over 28 weeks (AHOC)

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End point title

Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to FOP, Assessed by Daily NRS over 28 weeks (AHOC)

End point description

The pain NRS is a PRO used by participants to rate their pain associated with FOP. Participants were asked to rate their pain on a scale that ranges from “0” (no pain) to “10” (worst possible pain), where the highest score indicated worst outcome. Time-Weighted average (standardized AUC) of the change from baseline in daily pain due to FOP assessed by daily NRS over 28 weeks in AHOC analysis set is reported. AHOC analysis set included all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	21	18
Units: Score on a Scale
least squares mean (standard deviation)	-0.12 ( 0.221 )	-0.48 ( 0.237 )

REGN2477 10 mg/kg Q4W vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2651

Method

ANCOVA

Parameter type

Least Square Mean Difference

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-1.01

upper limit

0.29

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18^F-NaF PET at Week 8 (AHOC)

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End point title

Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18^F-NaF PET at Week 8 (AHOC)

End point description

Standardized uptake value max (SUVmax) was a measurement of the maximum radiopharmaceutical uptake within the volume of interest. Relative accuracy of a particular radiotracer in a particular tissue is determined by expressing the absolute accuracy (obtained in the primary outcome measure) in terms of percent difference between SUVmax values obtained from PET/CT. Percent Change in 18^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18^F-NaF PET in AHOC analysis set is reported. AHOC analysis set included all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 8

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	22	20
Units: Percent Change
least squares mean (standard error)	-11.6 ( 3.47 )	-33.7 ( 3.61 )

LS Mean Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

ANCOVA

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-22.1

Confidence interval

level

95%

sides

2-sided

lower limit

-32.3

upper limit

-12

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) as assessed by 18^F-NaFPET at Week 8 (AHO)

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End point title

Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) as assessed by 18^F-NaFPET at Week 8 (AHO)

End point description

Percent change in 18^F-NaF SUVmax of individual active HO site(s) as assessed by 18^F-NaF PET at Week 8 in AHO analysis set is reported. Active Heterotopic Ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 8

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	24	20
Units: Percent Change
least squares mean (standard error)	-6.6 ( 3.70 )	-22.3 ( 4.02 )

LS Mean Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0065 ^[8]

Method

ANCOVA

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-15.7

Confidence interval

level

95%

sides

2-sided

lower limit

-26.8

upper limit

-4.6

Notes
[8] - p-Value vs. Placebo

Secondary: Period 1: Change from Baseline in Number of HO lesions as Assessed by 18^F-NaF PET at Week 28 (AHOC)

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End point title

Period 1: Change from Baseline in Number of HO lesions as Assessed by 18^F-NaF PET at Week 28 (AHOC)

End point description

Change from baseline in number of HO lesions was assessed by 18^F-NaF PET at Week 28 in AHOC analysis set is reported. AHOC analysis set included all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	22	20
Units: HO Lesions
arithmetic mean (standard deviation)	-1.0 ( 2.66 )	-2.3 ( 2.24 )

Median Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2351 ^[9]

Method

ANCOVA

Parameter type

Median Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Notes
[9] - p-Value vs. Placebo; ANCOVA model on ranked response

Secondary: Period 1: Change from Baseline in Number of HO Lesions as Assessed by 18^F-NaF PET at Week 28 (AHO)

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End point title

Period 1: Change from Baseline in Number of HO Lesions as Assessed by 18^F-NaF PET at Week 28 (AHO)

End point description

Change from baseline in number of HO lesions was assessed by 18^F-NaF PET in AHO analysis set is reported. Active Heterotopic Ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	24	20
Units: HO Lesions
arithmetic mean (standard deviation)	-1.0 ( 2.59 )	-2.3 ( 2.24 )

Median Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1746 ^[10]

Method

ANCOVA

Parameter type

Median Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Notes
[10] - p-Value vs. Placebo; ANCOVA model on ranked response

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHOC)

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End point title

Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHOC)

End point description

Change from baseline in number of HO lesions was detectable by CT using AHOC analysis set is reported. AHOC analysis set included all randomized participants with the classic ACVR1 [R206H] mutation and who had at least one AHO at baseline, as defined by 18^F-NaF PET positivity; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHOC)	Period 1: REGN2477 10 mg/kg Q4W (AHOC)
Number of subjects analysed	22	20
Units: HO Lesions
arithmetic mean (standard deviation)	1.2 ( 2.00 )	-0.3 ( 1.34 )

Median Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHOC) v Period 1: REGN2477 10 mg/kg Q4W (AHOC)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0153 ^[11]

Method

ANCOVA

Parameter type

Median Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

Notes
[11] - p-Value vs. Placebo; ANCOVA model on ranked response

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHO)

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End point title

Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHO)

End point description

Change from baseline in number of HO lesions detectable by CT at Week 28 in AHO analysis set is reported. Active Heterotopic Ossification analysis set (AHO) included all randomized participants who had at least one active HO lesion at baseline; and was based on the treatment allocated (as randomized).

End point type

Secondary

End point timeframe

Week 28

End point values	Period 1: Placebo (AHO)	Period 1: REGN2477 10 mg/kg Q4W (AHO)
Number of subjects analysed	24	20
Units: HO Lesions
arithmetic mean (standard deviation)	1.2 ( 1.93 )	-0.3 ( 1.34 )

Median Difference vs. Placebo

Comparison groups

Period 1: Placebo (AHO) v Period 1: REGN2477 10 mg/kg Q4W (AHO)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0153 ^[12]

Method

ANCOVA

Parameter type

Median Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

Notes
[12] - p-Value vs. Placebo; ANCOVA model on ranked response

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[13]

End point description

Number of new HO lesions as assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: New HO lesions
New lesions	23	1

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared number of new lesions per patient by PET at week 28 (relative to baseline) and week 56 (relative to week 28).

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039 ^[14]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[14] - Week 56 vs. Week 28

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[15]

End point description

Percentage of participants with new HO lesions as assessed by CT at Week 56 Relative to Week 28 Scan is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Percentage of Participants
number (not applicable)
% of participants with new lesions	40.9	0.0

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared percent of participants with new lesions by CT at week 28 (relative to baseline) and week 56 (relative to week 28).

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0027 ^[16]

Method

Mcnemar

Confidence interval

Notes
[16] - Week 56 vs. Week 28

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[17]

End point description

Percentage of participants with new HO lesions as assessed by 18^F-NaF PET at Week 56 using AHO analysis set is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Percentage of Participants
number (not applicable)
% of participants with new lesions	40.9	4.5

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared percent of participants with new lesions by PET at week 28 (relative to baseline) and week 56 (relative to week 28).

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0047 ^[18]

Method

Mcnemar

Confidence interval

Notes
[18] - Week 56 vs. Week 28

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

End point description

Number of new HO lesions as assessed by CT only at week 56 relative to week 28 using AHO analysis set is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: New HO lesions
New lesions	22	0

Week 56 vs. Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039

Method

Wilcoxon signed rank test

Confidence interval

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

End point description

Percentage of participants with new HO lesions as assessed by CT only at Week 56 using AHO is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: Percentage of Participants
number (not applicable)
% of participants with new HO lesions	45.5	9.1

Week 56 vs. Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0209

Method

Mcnemar

Confidence interval

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Top of page

End point title

Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

End point description

Change from Week 28 to Week 56 as assessed by 18^F-NaF PET versus from Baseline to Week 28; COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: g.
arithmetic mean (standard deviation)	1.1 ( 1.93 )	-0.2 ( 0.61 )

Period 2 vs. Period 1

Statistical analysis description

Difference of Change from Week 28 to Week 56 versus from Baseline to Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[19]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[19] - Period 2 vs. Period 1

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by CT Scan at Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

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End point title

Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by CT Scan at Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

End point description

Change from Week 28 to Week 56 as assessed by CT Scan versus from Baseline to Week 28 is reported; COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: Cubic centimeter (cm^3)
arithmetic mean (standard deviation)	1.1 ( 1.93 )	-0.2 ( 0.61 )

Period 2 vs. Period 1

Statistical analysis description

Difference of Change from Week 28 to Week 56 versus from Baseline to Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[20]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[20] - Period 2 vs. Period 1

Secondary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Number of new HO lesions as assessed by CT at Week 56 relative to baseline. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Baseline, Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: New HO Lesions	2

No statistical analyses for this end point

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Number of new HO lesions as assessed by CT only at week 56 relative baseline is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: New HO Lesions	1

No statistical analyses for this end point

Secondary: Period 2: Percentage of Participants with New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants with New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Percentage of participants with new HO lesions as assessed by CT at week 56 relative to baseline were reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: Percentage of Participants
number (not applicable)	11.1

No statistical analyses for this end point

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NAF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Number of New HO Lesions as Assessed by 18^F-NAF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Number of new HO lesions as assessed by 18^F-NAF PET at week 56 relative to baseline is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: New HO Lesions	1

No statistical analyses for this end point

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Percentage of participants with new HO lesions as assessed by 18^F-NaF PET at week 56 relative to baseline. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: Percentage of Participants
number (not applicable)	5.6

No statistical analyses for this end point

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Total Volume of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[21]

End point description

Total volume of new HO lesions as assessed by CT at Week 56 relative to Week 28 scan. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Cubic centimeter (cm^3)
arithmetic mean (standard deviation)
Volume of new lesions	9.3 ( 19.66 )	0.0 ( 0.21 )

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared total new lesion volume per participant by CT at week 28 (relative to baseline) and week 56 (relative to week 28)

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0039 ^[22]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[22] - Week 56 vs. Week 28

Secondary: Period 2: Total Lesion Activity (TLA) Assessed by 18^F-NaF PET in New HO Lesions at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

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End point title

Period 2: Total Lesion Activity (TLA) Assessed by 18^F-NaF PET in New HO Lesions at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT) ^[23]

End point description

TLA is a measure of participant-level cumulative burden of metabolically active HO. Activity of individual HO lesions was calculated as the product of SUVmean and the PET volume of the active HO lesion. TLA was derived for each participant at each time point as the sum of HO lesion activity of individual target and new active HO lesions. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: g.
arithmetic mean (standard deviation)
TLA in new lesions	204.4 ( 442.35 )	13.2 ( 61.89 )

Placebo/REGN2477 10 mg/kg Q4W

Statistical analysis description

Compared total lesion activity per participant in new lesions by PET at week 28 (relative to baseline) and week 56 (relative to week 28)

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0273 ^[24]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[24] - Week 56 vs. Week 28

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in TLA as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

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End point title

Period 2 vs. Period 1: Percent Change From Week 28 in TLA as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

End point description

Percent Change from Week 28 to Week 56 versus from Baseline to Week 28 is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: Percent Change
arithmetic mean (standard deviation)	48.2 ( 156.17 )	-16.4 ( 33.81 )

Period 2 vs. Period 1

Statistical analysis description

Difference of Percent Change from Week 28 to Week 56 versus from Baseline to Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2123 ^[25]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[25] - Period 2 vs. Period 1

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in the Total Volume of HO Lesions as Assessed by CT to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

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End point title

Period 2 vs. Period 1: Percent Change From Week 28 in the Total Volume of HO Lesions as Assessed by CT to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

End point description

End point type

Secondary

End point timeframe

Week 28, Week 56

End point values	Period 1: Placebo (AHO)	Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	22	22
Units: Percent Change
arithmetic mean (standard deviation)	34.0 ( 129.39 )	2.2 ( 13.66 )

Period 2 vs. Period 1

Statistical analysis description

Difference of Percent Change from Week 28 to Week 56 versus from Baseline to Week 28

Comparison groups

Period 1: Placebo (AHO) v Period 2: Placebo/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1528 ^[26]

Method

Wilcoxon signed rank test

Confidence interval

Notes
[26] - Period 2 vs. Period 1

Secondary: Period 2: TLA in New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: TLA in New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Total Lesion Activity (TLA) is a measure of participant-level cumulative burden of metabolically active HO. TLA in New (Relative to Baseline) Lesions at Week 56 is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: g.
arithmetic mean (standard deviation)	0.7 ( 2.13 )

No statistical analyses for this end point

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

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End point title

Period 2: Total Volume of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

End point description

Total volume of new HO lesions as assessed by CT only at week 56 relative to baseline were reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: Cubic centimeter (cm^3)
arithmetic mean (standard deviation)	0.0 ( 0.02 )

No statistical analyses for this end point

Secondary: Period 2: Percent Change From Baseline in TLA as Assessed by 18^F-NaF PET to Week 56 (AHO COVID-19 mITT)

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End point title

Period 2: Percent Change From Baseline in TLA as Assessed by 18^F-NaF PET to Week 56 (AHO COVID-19 mITT)

End point description

Percent change from baseline in TLA as assessed by 18^F-NaF PET to week 56 were reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	17
Units: Percent Change
arithmetic mean (standard deviation)	-16.4 ( 53.10 )

No statistical analyses for this end point

Secondary: Period 2: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by CT to Week 56 (AHO COVID-19 mITT)

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End point title

Period 2: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by CT to Week 56 (AHO COVID-19 mITT)

End point description

Percent change from baseline in the total volume of HO lesions as assessed by CT to Week 56 were reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	18
Units: Percent Change
arithmetic mean (standard deviation)	2.6 ( 10.18 )

No statistical analyses for this end point

Secondary: Period 2: Percent Change From Week 28 in SUVmax as Assessed by 18^F-NaF to Week 56 (AHO COVID-19 mITT)

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End point title

Period 2: Percent Change From Week 28 in SUVmax as Assessed by 18^F-NaF to Week 56 (AHO COVID-19 mITT) ^[27]

End point description

Percent Change from Week 28 to Week 56 is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28 to Week 56

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	21
Units: Percent Change
arithmetic mean (standard deviation)	-16.8 ( 19.52 )	-30.3 ( 15.03 )

Period 2 vs. Period 1

Statistical analysis description

Compared percent change from week 28 to week 56 and from baseline to week 28

Comparison groups

Placebo v Placebo/REGN2477 10 mg/kg Q4W

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0209

Method

Wilcoxon signed rank test

Confidence interval

Secondary: Period 2: Percent Change From Baseline in 18^F-NaF PET SUVmax to Week 56 (AHO COVID-19 mITT)

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End point title

Period 2: Percent Change From Baseline in 18^F-NaF PET SUVmax to Week 56 (AHO COVID-19 mITT)

End point description

Percent change from baseline in 18^F-NaF PET SUVmax to week 56. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Baseline, Week 56

End point values	Period 2: REGN2477/REGN2477 10 mg/kg Q4W (AHO COVID-19 mITT)
Number of subjects analysed	17
Units: Percent Change
arithmetic mean (standard deviation)	-41.9 ( 29.16 )

No statistical analyses for this end point

Secondary: Period 2: Daily Average Pain due to FOP Measured Using the Daily NRS (AHO COVID-19 mITT)

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End point title

Period 2: Daily Average Pain due to FOP Measured Using the Daily NRS (AHO COVID-19 mITT) ^[28]

End point description

The pain NRS was a patient reported outcome used by participants to rate their pain associated with FOP. Participants were asked to rate their pain on a scale that ranges from "0" (no pain) to "10" (worst possible pain), where the highest score indicated worst outcome. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28 up to Week 56

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Score on a Scale
arithmetic mean (standard deviation)	1.79 ( 2.106 )	1.60 ( 1.969 )

No statistical analyses for this end point

Secondary: Period 2: Percentage of Participants With Flare-ups Assessed by Participant E-diary (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With Flare-ups Assessed by Participant E-diary (AHO COVID-19 mITT) ^[29]

End point description

Percentage of participants with flare-ups starting between week 28 and week 56 as assessed by participant E-diary is reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28 to Week 56

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Percentage of Participants
number (not applicable)	68.2	13.6

No statistical analyses for this end point

Secondary: Period 2: Percentage of Participants With Investigator-assessed Flare-ups (AHO COVID-19 mITT)

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End point title

Period 2: Percentage of Participants With Investigator-assessed Flare-ups (AHO COVID-19 mITT) ^[30]

End point description

Percentage of participants with investigator-assessed flare-ups were reported. COVID-19 Modified Intent-to-Treat set (COVID-19 mITT) included all AHO participants who received a treatment in Period 2 for whom at least 1 post-Week 28 scan was collected and the period between any consecutive doses was less than 9 weeks (63 days) before the 1st post-week 28 scan.

End point type

Secondary

End point timeframe

Week 28 to Week 56

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The REGN2477/REGN2477 arm was reported in a different end point.

End point values	Placebo	Placebo/REGN2477 10 mg/kg Q4W
Number of subjects analysed	22	22
Units: Percentage of Participants
number (not applicable)	45.5	13.6

No statistical analyses for this end point

Secondary: Periods 1, 2, and 3: Concentration of Total Activin A in Serum

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End point title

Periods 1, 2, and 3: Concentration of Total Activin A in Serum

End point description

Concentration of total activin A in serum over time is reported. The pharmacokinetic (PK) analysis set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration following the first dose of study drug. "Overall number of participants analyzed” are the participants who were evaluable for this outcome measure

End point type

Secondary

End point timeframe

Week 28, Week 56, Week 76

End point values	REGN2477 10 mg/kg Q4W (PK)
Number of subjects analysed	44
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard deviation)
Week 28 (n=38)	0.0550 ( 0.0147 )
Week 56 (n=31)	0.0505 ( 0.0175 )
Week 76 (n=16)	0.0496 ( 0.0148 )

No statistical analyses for this end point

Secondary: Periods 1, 2, and 3: Concentrations of Functional REGN2477 in Serum

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End point title

Periods 1, 2, and 3: Concentrations of Functional REGN2477 in Serum

End point description

Concentrations of REGN2477 capable of target binding were measured (functional drug). The pharmacokinetic (PK) analysis set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration following the first dose of study drug. "Overall number of participants analyzed” are the participants who were evaluable for this outcome measure

End point type

Secondary

End point timeframe

Week 28, Week 56, Week 76

End point values	REGN2477 10 mg/kg Q4W (PK)
Number of subjects analysed	44
Units: mg/L
arithmetic mean (standard deviation)
Week 28 (n=38)	114 ( 40.0 )
Week 56 (n=31)	113 ( 44.9 )
Week 76 (n=16)	115 ( 25.6 )

No statistical analyses for this end point

Secondary: Periods 1, 2, and 3: Number of Participants with Clinical Impact of Treatment-Emergent Anti-drug Antibodies (ADA) to REGN2477

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End point title

Periods 1, 2, and 3: Number of Participants with Clinical Impact of Treatment-Emergent Anti-drug Antibodies (ADA) to REGN2477

End point description

Immunogenicity was characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, >= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the REGN2477 ADA assay post first dose when baseline results = negative or missing. The Anti-Drug Antibody (ADA) analysis set included all participants who received study drug and had at least 1 non-missing ADA result following the first study dose. "Overall number of participants analyzed” are the participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Up to Week 76

End point values	Placebo/REGN2477 10 mg/kg Q4W (ADA)	REGN2477/REGN2477 10 mg/kg Q4W (ADA)
Number of subjects analysed	24	19
Units: Participants
Negative	0	0
Pre-existing Immunoreactivity	0	0
Treatment-Boosted Response	0	0
Treatment-Emergent Response	0	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study drug to end of study

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Placebo

Reporting group description

Participants received a single dose of placebo matched to REGN2477 intravenous (IV) infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Reporting group title

REGN2477/REGN2477 10 mg/kg Q4W

Reporting group description

Reporting group title

Placebo/REGN2477 10 mg/kg Q4W

Reporting group description

Participants who were in the placebo group in Period 1 crossed over to receive a single dose of REGN2477 IV infusion Q4W for additional 28 weeks during Period 2 followed by 20 weeks during Period 3. Participants could continue receiving REGN2477 every 4 weeks beyond week 76 provided that no safety signals were identified.

Reporting group title

REGN2477 10 mg/kg Q4W

Reporting group description

Participants received a single dose of REGN2477 10 milligrams per kilogram (mg/kg) IV infusion every 4 weeks (Q4W) for up to 28 weeks during Period 1.

Serious adverse events	Placebo	REGN2477/REGN2477 10 mg/kg Q4W	Placebo/REGN2477 10 mg/kg Q4W	REGN2477 10 mg/kg Q4W
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 24 (8.33%)	7 / 19 (36.84%)	6 / 24 (25.00%)	4 / 20 (20.00%)
number of deaths (all causes)	0	3	2	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Splenic rupture
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Intestinal obstruction
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Renal and urinary disorders
Renal colic
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perineal abscess
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	REGN2477/REGN2477 10 mg/kg Q4W	Placebo/REGN2477 10 mg/kg Q4W	REGN2477 10 mg/kg Q4W
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 24 (100.00%)	18 / 19 (94.74%)	24 / 24 (100.00%)	20 / 20 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Uterine leiomyoma
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Vascular disorders
Flushing
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	1	0	1
Hypertension
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2
Hot flush
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
General disorders and administration site conditions
Peripheral swelling
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	3	1	1	1
Pain
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	1	1	1	1
Malaise
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	0	1
Fatigue
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	1 / 24 (4.17%)	2 / 20 (10.00%)
occurrences all number	2	1	1	3
Vessel puncture site bruise
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
Asthenia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	2	1
Chest discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2
Chest pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Chills
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Feeling hot
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Inflammation
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Infusion site pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2
Medical device site bruise
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Non-cardiac chest pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2
Pyrexia
subjects affected / exposed	0 / 24 (0.00%)	7 / 19 (36.84%)	5 / 24 (20.83%)	3 / 20 (15.00%)
occurrences all number	0	8	8	7
Swelling
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	6	1	1
Reproductive system and breast disorders
Acquired phimosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Endometrial thickening
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Menstruation irregular
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0
Ovarian cyst
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	0	0	3	0
Perineal cyst
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Prostatitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	4 / 24 (16.67%)	5 / 19 (26.32%)	10 / 24 (41.67%)	10 / 20 (50.00%)
occurrences all number	7	45	34	32
Cough
subjects affected / exposed	2 / 24 (8.33%)	3 / 19 (15.79%)	3 / 24 (12.50%)	2 / 20 (10.00%)
occurrences all number	2	3	3	2
Dyspnoea
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	4	0	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	2	2	1	1
Nasal congestion
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	1	1	1	0
Atelectasis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Haemoptysis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	5
Nasal dryness
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Oropharyngeal discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Productive cough
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Rhinorrhoea
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	3	0	0
Sinus congestion
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	5	0	3	0
Somatic symptom disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Investigations
Crystal urine present
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1
Fibrin D dimer increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Platelet function test abnormal
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
SARS-CoV-2 test positive
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
White blood cell count increased
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	3 / 24 (12.50%)	2 / 19 (10.53%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	11	2	5	0
Extraskeletal ossification
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	2	1	2	0
Head injury
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	1	0	2	0
Post-traumatic pain
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	6 / 24 (25.00%)	0 / 20 (0.00%)
occurrences all number	3	1	11	0
Animal bite
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Arthropod bite
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Back injury
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Joint injury
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	3 / 24 (12.50%)	1 / 20 (5.00%)
occurrences all number	0	1	3	1
Limb injury
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Lower limb fracture
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Skin laceration
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	0	0	4	0
Post vaccination syndrome
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Tooth fracture
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Traumatic haematoma
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Vascular access site swelling
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Congenital, familial and genetic disorders
Gilbert's syndrome
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Sebaceous naevus
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	7 / 24 (29.17%)	8 / 19 (42.11%)	6 / 24 (25.00%)	10 / 20 (50.00%)
occurrences all number	14	47	50	28
Dizziness
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	3 / 24 (12.50%)	4 / 20 (20.00%)
occurrences all number	2	5	4	7
Paraesthesia
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	6	0	3	0
Presyncope
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	0	0	0
Neuralgia
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	2	0	0
Cervical radiculopathy
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Burning sensation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Dysgeusia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	20	0	8
Head discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Hypoaesthesia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Migraine
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	2	0	1
Post-traumatic headache
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	2 / 20 (10.00%)
occurrences all number	2	1	1	2
Increased tendency to bruise
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Iron deficiency anaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Lymph node pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Lymphadenitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Lymphadenopathy
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Microcytic anaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Ear and labyrinth disorders
Conductive deafness
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Ear pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Ear discomfort
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Ear pruritus
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Hyperacusis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Hypoacusis
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	2	1	0
Tinnitus
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Ocular hypertension
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Dry eye
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Photophobia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	2
Vision blurred
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	0	0	1
Diarrhoea
subjects affected / exposed	6 / 24 (25.00%)	2 / 19 (10.53%)	5 / 24 (20.83%)	5 / 20 (25.00%)
occurrences all number	8	8	8	6
Nausea
subjects affected / exposed	2 / 24 (8.33%)	2 / 19 (10.53%)	5 / 24 (20.83%)	3 / 20 (15.00%)
occurrences all number	4	3	6	7
Abdominal pain
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	2 / 24 (8.33%)	2 / 20 (10.00%)
occurrences all number	1	2	2	2
Abdominal pain lower
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	2 / 24 (8.33%)	1 / 20 (5.00%)
occurrences all number	1	0	6	1
Abdominal pain upper
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	2 / 24 (8.33%)	2 / 20 (10.00%)
occurrences all number	1	2	3	3
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	1	0	2	0
Mouth ulceration
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	0 / 24 (0.00%)	2 / 20 (10.00%)
occurrences all number	2	13	0	3
Abdominal discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Aphthous ulcer
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	0	7	3	0
Dental caries
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Dry mouth
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Dyspepsia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	1	1	1
Dysphagia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Flatulence
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Gastrointestinal disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Gastrointestinal pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Glossodynia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Gingival pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Haematochezia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Inguinal hernia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Irritable bowel syndrome
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Lip blister
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Noninfective gingivitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Oral disorder
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Oral discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Toothache
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	4 / 20 (20.00%)
occurrences all number	0	0	1	4
Vomiting
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	0	1	6	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	4 / 24 (16.67%)	2 / 19 (10.53%)	4 / 24 (16.67%)	2 / 20 (10.00%)
occurrences all number	8	3	16	2
Acne
subjects affected / exposed	3 / 24 (12.50%)	4 / 19 (21.05%)	12 / 24 (50.00%)	6 / 20 (30.00%)
occurrences all number	3	5	17	6
Erythema
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	2	1	4	0
Decubitus ulcer
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	2	2	0	2
Alopecia
subjects affected / exposed	1 / 24 (4.17%)	3 / 19 (15.79%)	5 / 24 (20.83%)	2 / 20 (10.00%)
occurrences all number	1	3	6	3
Dry skin
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	2 / 24 (8.33%)	3 / 20 (15.00%)
occurrences all number	1	1	2	3
Skin lesion
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	3 / 24 (12.50%)	0 / 20 (0.00%)
occurrences all number	1	1	3	0
Pruritus
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 24 (0.00%)	3 / 20 (15.00%)
occurrences all number	1	1	0	3
Hyperkeratosis
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	1	1	1	1
Acne cystic
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Ecchymosis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Dermal cyst
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Blister
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	2 / 20 (10.00%)
occurrences all number	0	1	1	3
Eczema
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	3	0	3
Hirsutism
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	3	1	1
Hyperhidrosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Intertrigo
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2
Hypertrichosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	4 / 24 (16.67%)	1 / 20 (5.00%)
occurrences all number	0	0	4	1
Nail bed bleeding
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	14	0	0
Madarosis
subjects affected / exposed	0 / 24 (0.00%)	8 / 19 (42.11%)	13 / 24 (54.17%)	6 / 20 (30.00%)
occurrences all number	0	9	13	6
Onychalgia
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	1	1	1
Perioral dermatitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Papule
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Onycholysis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Petechiae
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Rash vesicular
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Rash pruritic
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Rash papular
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2
Skin exfoliation
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Urticaria
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Skin ulcer
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	3 / 24 (12.50%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	3	1	1	0
Nephrolithiasis
subjects affected / exposed	3 / 24 (12.50%)	0 / 19 (0.00%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	3	0	2	0
Dysuria
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Proteinuria
subjects affected / exposed	2 / 24 (8.33%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	2	2	0	0
Pollakiuria
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Urinary retention
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	9 / 24 (37.50%)	9 / 19 (47.37%)	8 / 24 (33.33%)	7 / 20 (35.00%)
occurrences all number	13	24	16	8
Pain in extremity
subjects affected / exposed	9 / 24 (37.50%)	8 / 19 (42.11%)	6 / 24 (25.00%)	5 / 20 (25.00%)
occurrences all number	19	22	18	6
Myalgia
subjects affected / exposed	3 / 24 (12.50%)	3 / 19 (15.79%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	3	4	4	1
Neck pain
subjects affected / exposed	3 / 24 (12.50%)	4 / 19 (21.05%)	2 / 24 (8.33%)	4 / 20 (20.00%)
occurrences all number	5	13	2	5
Muscle swelling
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	5	0	0	1
Back pain
subjects affected / exposed	1 / 24 (4.17%)	6 / 19 (31.58%)	7 / 24 (29.17%)	4 / 20 (20.00%)
occurrences all number	1	13	9	4
Joint swelling
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	3 / 20 (15.00%)
occurrences all number	1	1	1	3
Spinal pain
subjects affected / exposed	1 / 24 (4.17%)	4 / 19 (21.05%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	4	10	3	0
Calcification of muscle
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Arthritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Temporomandibular joint syndrome
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	1	1	0	0
Flank pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Exostosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Coccydynia
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	3	1	0
Inguinal mass
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Muscle spasms
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	1 / 24 (4.17%)	2 / 20 (10.00%)
occurrences all number	0	3	1	2
Muscular weakness
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Joint noise
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	1
Musculoskeletal discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	2 / 24 (8.33%)	1 / 20 (5.00%)
occurrences all number	0	2	3	1
Pain in jaw
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Tendon pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	5 / 24 (20.83%)	9 / 19 (47.37%)	5 / 24 (20.83%)	3 / 20 (15.00%)
occurrences all number	7	14	6	5
Urinary tract infection
subjects affected / exposed	3 / 24 (12.50%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	4	0	2	0
Gastroenteritis
subjects affected / exposed	1 / 24 (4.17%)	2 / 19 (10.53%)	2 / 24 (8.33%)	2 / 20 (10.00%)
occurrences all number	1	2	2	2
Influenza
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	1	0	1	1
Pharyngitis
subjects affected / exposed	1 / 24 (4.17%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	1	1	1	0
Sinusitis
subjects affected / exposed	1 / 24 (4.17%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	1	0	1	1
Abdominal abscess
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	1	2	0
Abscess limb
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	4 / 24 (16.67%)	2 / 20 (10.00%)
occurrences all number	0	24	4	3
Anorectal cellulitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Anal abscess
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	3 / 24 (12.50%)	1 / 20 (5.00%)
occurrences all number	0	3	4	1
Abscess rupture
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
COVID-19
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	1	2	0
Folliculitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	3 / 24 (12.50%)	3 / 20 (15.00%)
occurrences all number	0	2	3	4
Conjunctivitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	1	0	2
Cellulitis orbital
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Furuncle
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	13	1	0
Groin abscess
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	3	0	0
Hordeolum
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Infected bite
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Infected dermal cyst
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	2	0
Otitis externa
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Otitis media acute
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	3	1	0
Paronychia
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	4	1	0
Perirectal abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Pneumonia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1
Respiratory tract infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0
Pustule
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Skin infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Skin bacterial infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	2	1	0
Rhinitis
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	2 / 24 (8.33%)	4 / 20 (20.00%)
occurrences all number	0	7	3	5
Subcutaneous abscess
subjects affected / exposed	0 / 24 (0.00%)	3 / 19 (15.79%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	6	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	1	2	0
Tooth infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	0	0	2	0
Tooth abscess
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	0 / 20 (0.00%)
occurrences all number	0	1	1	0
Vaginal infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	0	1	1
Viral upper respiratory tract infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	2 / 24 (8.33%)	1 / 20 (5.00%)
occurrences all number	0	0	2	1
Vulval abscess
subjects affected / exposed	0 / 24 (0.00%)	2 / 19 (10.53%)	0 / 24 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	2	0	0
Vulvitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 19 (5.26%)	1 / 24 (4.17%)	1 / 20 (5.00%)
occurrences all number	0	2	1	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 24 (8.33%)	0 / 19 (0.00%)	2 / 24 (8.33%)	0 / 20 (0.00%)
occurrences all number	2	0	2	0
Hypercholesterolaemia
subjects affected / exposed	0 / 24 (0.00%)	0 / 19 (0.00%)	0 / 24 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

10 Sep 2018

Protocol Amendment 1: The purpose of this amendment 1 Global was to remove the requirement that subjects have the specific classic ACVR1[R206H] mutation. This change was based on in vitro studies which demonstrated that different mutations in ACVR1 receptors transduced bone morphogenic protein signaling when stimulated with Activin A. These results indicated that REGN2477 may be effective for all FOP mutations. This change expands the scope of the study to include subjects with a clinical diagnosis of FOP who may have different ACVR1 mutations. To support interpretation of the study results, all subjects will have their ACVR1 gene sequenced during the study (mandatory). The primary statistical analyses for the study was based on the original study design, not the expanded study population.

29 Nov 2018

Protocol Amendment 2: The purpose of this amendment was to add individual level dose modification criteria, clarify the study level dose modification, and specify that a pregnancy will be tracked until delivery along with a 3-month postnatal follow-up period for the infant, in response to a health authority requests.

15 Feb 2019

Protocol Amendment 3: The purpose of this amendment was to revise the protocol to reflect new safety information relating to a potential risk for epistaxis. To mitigate the potential risk for epistaxis, exclusion criteria were added.

21 Jun 2019

Protocol Amendment 4: This is a non-substantial amendment to change the hierarchy order of statistical testing for the primary efficacy and key secondary endpoints in response to comments from a health authority. The order of statistical testing of the primary efficacy and key secondary endpoints is: Baseline-Active heterotopic ossification (AHO) analysis set first and Baseline-Active HO Classic ACVR1[R206H] Mutation (AHOC) analysis set second.

25 Oct 2019

Protocol Amendment 5: The purpose of this amendment was to revise the description of study treatment based on a new liquid formulation. The option for subcutaneous (SC) administration is removed as the concentration of the current formulation is not suitable for SC use.

22 May 2020

Protocol Amendment 6: The purpose of this amendment was to account for the COVID-19 pandemic and to minimize the risks to the patients in the study as well as healthcare providers by allowing flexibility in the visit schedule while social distancing suggestions are in place. Allowing for this flexibility does not increase the risk of participating in this study as there will be continued contact between the patients and study personnel despite postponement of in-person clinic visits. In addition, this amendment seeks to update the planned analysis for Period 2 (open-label treatment period; week 56) based on the primary analysis results from Period 1 (double-blind, placebo-controlled period; week 28). These data prompted definition of a separate study hypothesis to “treatment with REGN2477 prevents the formation of new HO lesion in patients with FOP” and addition of new endpoints to test this separate hypothesis for Period 2 (week 56).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Dosing of garetosmab (REGN2477) was put on hold on 30 Oct 2020. Study participants continued to be followed for safety until end of study on 16 Sep 2021.

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Clinical trials

Clinical Trial Results: A randomized, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and effects on heterotopic bone formation of REGN2477 in patients with Fibrodysplasia Ossificans Progressiva

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Period 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Primary: Period 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Primary: Period 1: Number of Participants with TEAEs by Severity

Primary: Period 1: Number of Participants with TEAEs by Severity

Primary: Period 1: Time-Weighted Average (Standardized Area Under the Curve [AUC]) of the Percent Change From Baseline in Total Lesion Activity by Fluorine-18-labeled Sodium Fluoride (18^F-NaF) Positron Emission Tomography (PET) over 28 weeks (AHO)

Primary: Period 1: Time-Weighted Average (Standardized Area Under the Curve [AUC]) of the Percent Change From Baseline in Total Lesion Activity by Fluorine-18-labeled Sodium Fluoride (18^F-NaF) Positron Emission Tomography (PET) over 28 weeks (AHO)

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by Computed Tomography (CT) at Week 28 (AHO)

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by Computed Tomography (CT) at Week 28 (AHO)

Primary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Primary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Primary: Period 1: Time-weighted Average (Standardized AUC) of the Percent Change From Baseline in Total Lesion Activity Assessed by 18^F-NaF PET over 28 weeks (AHOC)

Primary: Period 1: Time-weighted Average (Standardized AUC) of the Percent Change From Baseline in Total Lesion Activity Assessed by 18^F-NaF PET over 28 weeks (AHOC)

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by CT at Week 28 (AHOC)

Primary: Period 1: Percent Change from Baseline in the Total Volume of HO Lesions as Assessed by CT at Week 28 (AHOC)

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to Fibrodysplasia Ossificans Progressiva (FOP) Assessed by Daily Numeric Rating Scale (NRS) over 28 weeks (AHO)

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to Fibrodysplasia Ossificans Progressiva (FOP) Assessed by Daily Numeric Rating Scale (NRS) over 28 weeks (AHO)

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to FOP, Assessed by Daily NRS over 28 weeks (AHOC)

Secondary: Period 1: Time-weighted Average (Standardized AUC) of the Change from Baseline in Daily Pain due to FOP, Assessed by Daily NRS over 28 weeks (AHOC)

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18^F-NaF PET at Week 8 (AHOC)

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) assessed by 18^F-NaF PET at Week 8 (AHOC)

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) as assessed by 18^F-NaFPET at Week 8 (AHO)

Secondary: Period 1: Percent Change from Baseline in 18^F-NaF SUVmax of Individual Active HO Site(s) as assessed by 18^F-NaFPET at Week 8 (AHO)

Secondary: Period 1: Change from Baseline in Number of HO lesions as Assessed by 18^F-NaF PET at Week 28 (AHOC)

Secondary: Period 1: Change from Baseline in Number of HO lesions as Assessed by 18^F-NaF PET at Week 28 (AHOC)

Secondary: Period 1: Change from Baseline in Number of HO Lesions as Assessed by 18^F-NaF PET at Week 28 (AHO)

Secondary: Period 1: Change from Baseline in Number of HO Lesions as Assessed by 18^F-NaF PET at Week 28 (AHO)

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHOC)

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHOC)

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHO)

Secondary: Period 1: Change from Baseline in Number of HO Lesions Detectable by CT at Week 28 (AHO)

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by CT Only at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by CT Scan at Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Change From Week 28 in Number of Active HO Lesions as Assessed by CT Scan at Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants with New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants with New HO Lesions as Assessed by CT at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NAF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Number of New HO Lesions as Assessed by 18^F-NAF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Percentage of Participants With New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Total Lesion Activity (TLA) Assessed by 18^F-NaF PET in New HO Lesions at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2: Total Lesion Activity (TLA) Assessed by 18^F-NaF PET in New HO Lesions at Week 56 Relative to Week 28 Scan (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in TLA as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in TLA as Assessed by 18^F-NaF PET to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in the Total Volume of HO Lesions as Assessed by CT to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2 vs. Period 1: Percent Change From Week 28 in the Total Volume of HO Lesions as Assessed by CT to Week 56 (Period 2) Versus the Same Participants Between Baseline and Week 28 (Period 1) (AHO COVID-19 mITT)

Secondary: Period 2: TLA in New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: TLA in New HO Lesions as Assessed by 18^F-NaF PET at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Total Volume of New HO Lesions as Assessed by CT Only at Week 56 Relative to Baseline (AHO COVID-19 mITT)

Secondary: Period 2: Percent Change From Baseline in TLA as Assessed by 18^F-NaF PET to Week 56 (AHO COVID-19 mITT)

Secondary: Period 2: Percent Change From Baseline in TLA as Assessed by 18^F-NaF PET to Week 56 (AHO COVID-19 mITT)

Secondary: Period 2: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by CT to Week 56 (AHO COVID-19 mITT)

Secondary: Period 2: Percent Change From Baseline in the Total Volume of HO Lesions as Assessed by CT to Week 56 (AHO COVID-19 mITT)

Clinical Trial Results:
A randomized, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and effects on heterotopic bone formation of REGN2477 in patients with Fibrodysplasia Ossificans Progressiva