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Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Mechanistic Insight and Dosage Optimization Study of the Efficacy and Safety of VIB4920 in Patients with Rheumatoid Arthritis (RA)

Summary
EudraCT number	2019-003697-70
Trial protocol	PL
Global end of trial date	28 Dec 2021

Results information
Results version number	v1(current)
This version publication date	01 Jan 2023
First version publication date	01 Jan 2023
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

VIB4920.P2.S3

ISRCTN number

US NCT number

NCT04163991

WHO universal trial number (UTN)

Sponsor organisation name

Horizon Therapeutics USA, Inc.

Sponsor organisation address

1 Horizon Way , Deerfield, IL, United States, 60015-3888

Public contact

Ilias Alevizos, PhD, DMD, Viela Bio (acquired by Horizon Therapeutics), +1 866-479-6742, clinicaltrials@horizontherapeutics.com

Scientific contact

Ilias Alevizos, PhD, DMD, Viela Bio (acquired by Horizon Therapeutics), +1 866-479-6742, clinicaltrials@horizontherapeutics.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

28 Dec 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

• To evaluate the effect of VIB4920 on disease activity as assessed by a composite measure in subjects with adult-onset RA. • To evaluate the safety and tolerability of VIB4920 in subjects with adult-onset RA.

Protection of trial subjects

The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Council for Harmonisation (ICH)/Good Clinical Practice (GCP), applicable regulatory requirements, and the Sponsor’s policy on Ethical Interactions. Written and/or oral information about the nature, purpose, possible risk, and benefit of the study was provided to all participants in a language understandable by the participants. Participants were also notified that they were free to discontinue from the study at any time. Written informed consent was obtained from each participant before any study procedures or assessments were performed.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Dec 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 63

Country: Number of subjects enrolled

United States: 15

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

Screening details

After a screening period of up to 28 days, eligible participants were randomized in a 1:1:1:1:1 ratio into 5 cohorts.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

This was a double-blind study in which VIB4920 and the saline placebo were not identical in appearance. For maintaining the blinding of the participants, investigators, site staff, Sponsor, contract research organization, and staff, a local unblinded pharmacy staff member was nominated by each site and had the responsibility of allocating, dispensing, and preparing the investigational product (IP), and covering the intravenous (IV) bags with an opaque bag to maintain the blind.

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.

Arm type

Placebo

Investigational medicinal product name

0.9% saline for IV infusion

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

VIB4920 3000 mg Once

Arm description

Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.

Arm type

Experimental

Investigational medicinal product name

VIB4920

Investigational medicinal product code

Other name

MEDI4920, dazodalibep

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

Investigational medicinal product name

0.9% saline for IV infusion

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

VIB4920 1500 mg Twice

Arm description

Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.

Arm type

Experimental

Investigational medicinal product name

VIB4920

Investigational medicinal product code

Other name

MEDI4920, dazodalibep

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

Investigational medicinal product name

0.9% saline for IV infusion

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

VIB4920 3000 mg Twice

Arm description

Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.

Arm type

Experimental

Investigational medicinal product name

VIB4920

Investigational medicinal product code

Other name

MEDI4920, dazodalibep

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

Investigational medicinal product name

0.9% saline for IV infusion

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

VIB4920 1500 mg 4 Times

Arm description

Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57.

Arm type

Experimental

Investigational medicinal product name

VIB4920

Investigational medicinal product code

Other name

MEDI4920, dazodalibep

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IP was infused using an IV infusion pump.

Number of subjects in period 1	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Started	16	16	16	15	15
Completed	15	13	11	12	14
Not completed	1	3	5	3	1
Consent withdrawn by subject	1	1	3	1	1
Adverse Event	-	-	-	1	-
Death	-	-	1	-	-
Lost to follow-up	-	1	-	-	-
Other, Not Specified	-	1	1	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.

Reporting group title

VIB4920 3000 mg Once

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.

Reporting group title

VIB4920 1500 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 3000 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 1500 mg 4 Times

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57.

Reporting group values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times	Total
Number of subjects	16	16	16	15	15	78
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	56.3 ( 14.0 )	53.2 ( 10.7 )	59.0 ( 12.2 )	56.5 ( 12.2 )	56.4 ( 15.2 )	-
Gender categorical
Units: Subjects
Female	12	14	11	13	12	62
Male	4	2	5	2	3	16
Ethnicity
Units: Subjects
Hispanic or Latino	1	1	1	0	0	3
Not Hispanic or Latino	15	15	15	15	15	75
Race
Units: Subjects
Black or African American	2	0	0	1	1	4
White	14	16	15	14	14	73
Other, Not Specified	0	0	1	0	0	1
Disease Activity Score 28 C-reactive Protein (DAS28-CRP)
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity.
Units: score on a scale
arithmetic mean (standard deviation)	5.443 ( 1.066 )	5.473 ( 0.883 )	5.945 ( 0.736 )	5.452 ( 0.644 )	5.761 ( 0.711 )	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.

Reporting group title

VIB4920 3000 mg Once

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.

Reporting group title

VIB4920 1500 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 3000 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 1500 mg 4 Times

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57.

Primary: Change From Baseline to Day 113 in DAS28-CRP

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End point title

Change From Baseline to Day 113 in DAS28-CRP

End point description

The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity. Results are from a mixed-effect model for repeated measures (MMRM) analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model. Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.

End point type

Primary

End point timeframe

Day 1 (Baseline), Day 113

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	15	14	15	14	14
Units: score on a scale
least squares mean (standard error)	-1.06 ( 0.26 )	-1.90 ( 0.27 )	-1.87 ( 0.27 )	-1.87 ( 0.27 )	-1.83 ( 0.28 )

Statistical Analysis 1

Statistical analysis description

Least Squares (LS) Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Once

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0296 ^[1]

Method

MMRM

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-0.84

Confidence interval

level

90%

sides

2-sided

lower limit

-1.47

upper limit

-0.21

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[1] - Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.

Statistical Analysis 2

Statistical analysis description

LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0355 ^[2]

Method

MMRM

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-0.81

Confidence interval

level

90%

sides

2-sided

lower limit

-1.44

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[2] - Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.

Statistical Analysis 3

Statistical analysis description

LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0364 ^[3]

Method

MMRM

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-0.81

Confidence interval

level

90%

sides

2-sided

lower limit

-1.44

upper limit

-0.18

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[3] - Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.

Statistical Analysis 4

Statistical analysis description

LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg 4 Times

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0478 ^[4]

Method

MMRM

Parameter type

Least Squares (LS) Mean Difference

Point estimate

-0.77

Confidence interval

level

90%

sides

2-sided

lower limit

-1.41

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[4] - Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESIs)

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End point title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESIs) ^[5] ^[6]

End point description

Adverse event (AE): any untoward medical occurrence associated with the use of an intervention in humans, whether or not it is considered intervention-related. Serious adverse event (SAE): AE resulting in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity; congenital anomaly/birth defect; other important medical event jeopardizing the participant's well being. AEs of special interest (AESIs) include: thrombotic and embolic events; anaphylaxis and clinically significant (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) hypersensitivity reactions; severe infusion-related reactions (CTCAE Grade 3 or higher); immune complex disease; severe (CTCAE Grade 3 or higher) and/or opportunistic infections; hepatic function abnormality meeting the definition of Hy’s Law; malignant neoplasm. (CTCAE Grade 3=Severe; Grade 4=Life-threatening; Grade 5=Fatal.)

End point type

Primary

End point timeframe

From first dose of study drug through Day 309 ± 7 days

Notes
[5] - 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: Descriptive statistics are presented per protocol.
[6] - 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: Due to EudraCT system limitations, reporting of data for the "VIB4920 1500 mg Twice" and "VIB4920 3000 mg Once" arms was not possible. Please see the attached Word document in this endpoint for full data reporting.

End point values	Placebo	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[7]	13 ^[8]	14 ^[9]
Units: participants
At least 1 event	10	11	11
At least 1 study drug-related event	4	2	2
At least 1 event of ≥ Grade 3 severity	0	0	0
Death (Grade 5 severity)	0	0	0
At least 1 serious event	0	0	1
At least 1 serious and/or ≥ Grade 3 severity event	0	0	0
At least 1 related serious event	0	0	0
At least 1 event leading to study drug discontinue	0	0	0
At least 1 event of special interest	0	0	0

Attachments

Untitled (Filename: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)....docx)

Notes
[7] - Participants who received any dose of study drug, analyzed according to treatment actually received.
[8] - Participants who received any dose of study drug, analyzed according to treatment actually received.
[9] - Participants who received any dose of study drug, analyzed according to treatment actually received.

No statistical analyses for this end point

Secondary: Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)

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End point title

Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) ^[10]

End point description

PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. n=participants with an assessment at given dose time points by group.

End point type

Secondary

End point timeframe

Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d

Notes
[10] - 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: PK analyses were only performed for participants who received active study drug. In addition, due to EudraCT system limitations, reporting of data for the "VIB4920 1500 mg Twice" arm was not possible. Please see the attached Word document in this endpoint for full data reporting.

End point values	VIB4920 3000 mg Once	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[11]	13	14
Units: μg/mL
arithmetic mean (standard deviation)
Dose 1; n=16, 13, 13	877 ( 204 )	860 ( 275 )	421 ( 102 )
Dose 2; n=0, 13, 13	9999 ( 9999 )	1050 ( 349 )	564 ( 163 )
Dose 3; n=0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	601 ( 181 )
Dose 4; n=0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	568 ( 140 )

Attachments

Untitled (Filename: PK of VIB4920_Maximum Observed Concentration (Cmax).docx)

Notes
[11] - 9999=not applicable (0 participants analyzed).

No statistical analyses for this end point

Secondary: PK of VIB4920: Time to Cmax (Tmax)

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End point title

PK of VIB4920: Time to Cmax (Tmax) ^[12]

End point description

End point type

Secondary

End point timeframe

Notes
[12] - 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: PK analyses were only performed for participants who received active study drug. In addition, due to EudraCT system limitations, reporting of data for the "VIB4920 1500 mg Twice" arm was not possible. Please see the attached Word document in this endpoint for full data reporting.

End point values	VIB4920 3000 mg Once	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[13]	13 ^[14]	14 ^[15]
Units: day
median (full range (min-max))
Dose 1; n=16, 13, 13	0.0899 (0.0868 to 0.100)	0.0875 (0.0840 to 0.0917)	0.0903 (0.0840 to 0.108)
Dose 2; n=0, 13, 13	9999 (9999 to 9999)	0.0667 (0.0486 to 0.0882)	0.0486 (0.0437 to 0.0521)
Dose 3; n=0, 0, 14	9999 (9999 to 9999)	9999 (9999 to 9999)	0.0472 (0.0438 to 0.0486)
Dose 4; n=0, 0, 14	9999 (9999 to 9999)	9999 (9999 to 9999)	0.0667 (0.0486 to 0.0708)

Attachments

Untitled (Filename: PK of VIB4920_Time to Cmax (Tmax).docx)

Notes
[13] - 9999=not applicable (0 participants analyzed).
[14] - 9999=not applicable (0 participants analyzed).
[15] - 9999=not applicable (0 participants analyzed).

No statistical analyses for this end point

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)

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End point title

PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) ^[16]

End point description

End point type

Secondary

End point timeframe

Notes
[16] - 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: PK analyses were only performed for participants who received active study drug. In addition, due to EudraCT system limitations, reporting of data for the "VIB4920 1500 mg Twice" arm was not possible. Please see the attached Word document in this endpoint for full data reporting.

End point values	VIB4920 3000 mg Once	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[17]	13 ^[18]	14 ^[19]
Units: μg·day/mL
arithmetic mean (standard deviation)
Dose 1; n=16, 13, 13	7350 ( 1380 )	7870 ( 2570 )	2960 ( 604 )
Dose 2; n=0, 13, 13	9999 ( 9999 )	10000 ( 3320 )	4060 ( 1290 )
Dose 3; n=0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	6350 ( 1840 )
Dose 4; n=0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	5770 ( 1110 )

Attachments

Untitled (Filename: PK of VIB4920_Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration.docx)

Notes
[17] - 9999=not applicable (0 participants analyzed).
[18] - 9999=not applicable (0 participants analyzed).
[19] - 9999=not applicable (0 participants analyzed).

No statistical analyses for this end point

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)

Top of page

End point title

PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) ^[20]

End point description

PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points. n=participants with an assessment at given dose time points by group.

End point type

Secondary

End point timeframe

Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), Day 56

Notes
[20] - 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: PK analyses were only performed for participants who received active study drug.

End point values	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[21]	15 ^[22]	13 ^[23]	0 ^[24]
Units: μg·day/mL
arithmetic mean (standard deviation)
Dose 1; n=16, 15, 13, 0	7280 ( 1370 )	4280 ( 1280 )	7870 ( 2570 )	( )
Dose 2; n=0, 14, 13, 0	9999 ( 9999 )	5310 ( 2000 )	9910 ( 3250 )	( )
Dose 3; n=0, 0, 0, 0	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	( )
Dose 4; n=0, 0, 0, 0	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	( )

Notes
[21] - 9999=not applicable (0 participants analyzed).
[22] - 9999=not applicable (0 participants analyzed).
[23] - 9999=not applicable (0 participants analyzed).
[24] - Per protocol, due to the nature of the dosing and sampling for this arm, the analysis was not done.

No statistical analyses for this end point

Secondary: PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4

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End point title

PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 ^[25]

End point description

End point type

Secondary

End point timeframe

Notes
[25] - 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: PK analyses were only performed for participants who received active study drug.

End point values	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	15 ^[26]	15 ^[27]	13 ^[28]	14 ^[29]
Units: mL/day
arithmetic mean (standard deviation)
Dose 1 (CL); n=15, 15, 13, 0	430 ( 91.9 )	371 ( 92.5 )	417 ( 144 )	99999 ( 99999 )
Dose 2 (CLss); n=0, 14, 13, 0	9999 ( 9999 )	314 ( 104 )	340 ( 140 )	99999 ( 99999 )
Dose 3 (CLss); n=0, 0, 0, 0	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	99999 ( 99999 )
Dose 4 (CLss); n=0, 0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	294 ( 49.8 )

Notes
[26] - 9999=not applicable (0 participants analyzed).
[27] - 9999=not applicable (0 participants analyzed).
[28] - 9999=not applicable (0 participants analyzed).
[29] - 99999=due to the nature of dosing/sampling for this arm, analysis was done for Dose 4 only.

No statistical analyses for this end point

Secondary: PK of VIB4920: Terminal Elimination Half-Life (t1/2)

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End point title

PK of VIB4920: Terminal Elimination Half-Life (t1/2) ^[30]

End point description

End point type

Secondary

End point timeframe

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: PK analyses were only performed for participants who received active study drug.

End point values	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16 ^[31]	15 ^[32]	14 ^[33]	14 ^[34]
Units: day
arithmetic mean (standard deviation)
Dose 1; n=16, 15, 13, 0	9.27 ( 1.61 )	9.06 ( 1.98 )	9.02 ( 1.06 )	99999 ( 99999 )
Dose 2; n=0, 14, 13, 0	9999 ( 9999 )	9.55 ( 1.51 )	9.88 ( 1.41 )	99999 ( 99999 )
Dose 3; n=0, 0, 0, 0	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	99999 ( 99999 )
Dose 4; n=0, 0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	10.5 ( 2.06 )

Notes
[31] - 9999=not applicable (0 participants analyzed).
[32] - 9999=not applicable (0 participants analyzed).
[33] - 9999=not applicable (0 participants analyzed).
[34] - 99999=due to the nature of dosing/sampling for this arm, analysis was done for Dose 4 only.

No statistical analyses for this end point

Secondary: PK of VIB4920: Volume of Distribution at Steady State (Vss)

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End point title

PK of VIB4920: Volume of Distribution at Steady State (Vss) ^[35]

End point description

End point type

Secondary

End point timeframe

Notes
[35] - 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: PK analyses were only performed for participants who received active study drug.

End point values	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	15 ^[36]	15 ^[37]	13 ^[38]	14 ^[39]
Units: day
arithmetic mean (standard deviation)
Dose 1; n=15, 15, 13, 0	4350 ( 1300 )	3750 ( 601 )	4540 ( 1470 )	99999 ( 99999 )
Dose 2; n=0, 14, 13, 0	9999 ( 9999 )	3490 ( 926 )	3600 ( 1720 )	99999 ( 99999 )
Dose 3; n=0, 0, 0, 0	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	99999 ( 99999 )
Dose 4; n=0, 0, 0, 14	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	3210 ( 865 )

Notes
[36] - 9999=not applicable (0 participants analyzed).
[37] - 9999=not applicable (0 participants analyzed).
[38] - 9999=not applicable (0 participants analyzed).
[39] - 99999=due to the nature of dosing/sampling for this arm, analysis was done for Dose 4 only.

No statistical analyses for this end point

Secondary: Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time

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End point title

Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time

End point description

Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit. Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. n=Participants with an assessment at given time point by group.

End point type

Secondary

End point timeframe

Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16	16	16	15	15
Units: ng/mL
arithmetic mean (standard deviation)
Change at Day 15; n=16, 16, 16, 13, 14	4.6759 ( 3.6596 )	30.7744 ( 7.4954 )	36.0088 ( 14.4324 )	28.2492 ( 10.4252 )	33.9007 ( 8.7777 )
Change at Day 29; n=16, 15, 15, 14, 14	4.8431 ( 3.3770 )	67.5427 ( 16.4322 )	66.7047 ( 15.3708 )	68.0636 ( 28.6523 )	68.1386 ( 12.1314 )
Change at Day 57; n=16, 15, 15, 14, 14	0.8150 ( 1.6053 )	64.4177 ( 16.4322 )	62.5560 ( 14.4445 )	63.6939 ( 25.5500 )	64.1329 ( 12.4842 )
Change at Day 85; n=15, 15, 15, 15, 14	0.4483 ( 1.1842 )	53.1583 ( 20.6513 )	77.5360 ( 18.7440 )	57.2587 ( 20.0742 )	69.8821 ( 19.2623 )
Change at Day 113; n=15, 14, 15, 14, 14	0.3420 ( 1.3246 )	21.4686 ( 19.3705 )	75.4407 ( 18.2921 )	53.4514 ( 26.2712 )	68.5636 ( 19.3458 )
Change at Day 141; n=15, 15, 14, 15, 14	0.2547 ( 0.9863 )	1.6517 ( 3.7565 )	55.4204 ( 28.9470 )	53.2827 ( 31.6165 )	52.3943 ( 29.4422 )
Change at Day 169; n=14, 15, 14, 15, 13	0.3114 ( 1.1653 )	0 ( 0 )	21.1296 ( 27.1973 )	18.3170 ( 20.2842 )	23.5727 ( 26.0510 )
Change at Day 197; n=14, 14, 14, 15, 14	0.2757 ( 1.0316 )	0 ( 0 )	4.4354 ( 9.9146 )	2.5057 ( 4.4880 )	4.6343 ( 5.3603 )
Change at Day 225; n=14, 14, 14, 15, 14	0.2450 ( 0.9167 )	3.1418 ( 11.7555 )	-0.4043 ( 1.5127 )	-0.0137 ( 1.1940 )	-0.2971 ( 0.8718 )
Change at Day 253; n=14, 14, 13, 13, 13	0.3436 ( 1.2855 )	0 ( 0 )	-0.5946 ( 2.1439 )	-0.5292 ( 1.9082 )	-0.9485 ( 2.3281 )
Change at Day 281; n=14, 13, 10, 14, 13	-0.0343 ( 0.1283 )	0 ( 0 )	-0.5640 ( 1.7835 )	-0.4729 ( 1.7693 )	-0.9485 ( 2.3281 )
Change at Day 309; n=14, 12, 10, 12, 13	-0.5654 ( 2.1154 )	0 ( 0 )	-0.5720 ( 1.8088 )	-0.7833 ( 2.7135 )	-0.9485 ( 2.3281 )

No statistical analyses for this end point

Secondary: Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920

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End point title

Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 ^[40]

End point description

ADA positive at any time: observed at least once during the study (baseline included). Treatment-emergent ADA: ADA positive post-baseline only or boosted pre-existing ADA during the study period. Persistent positive: treatment-induced ADA positive at ≥ 2 post-baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive: treatment-induced ADA post-baseline positive but does not fulfill the criteria of persistent positive. Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received. Participants who received active study drug.

End point type

Secondary

End point timeframe

Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days)

Notes
[40] - 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: ADA analyses were only performed for participants who received active study drug. In addition, due to EudraCT system limitations, reporting of data for the "VIB4920 1500 mg Twice" and "VIB4920 3000 mg Once" arms was not possible. Please see the attached Word document in this endpoint for full data reporting.

End point values	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	13	14
Units: percentage of participants
number (not applicable)
ADA positive at any time	38.5	28.6
Baseline ADA positive	0	0
Baseline only ADA positive	0	0
Post-baseline ADA positive	38.5	28.6
Treatment-emergent ADA	38.5	28.6
Persistent positive	0	0
Transient positive	38.5	28.6

Attachments

Untitled (Filename: Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920.docx)

No statistical analyses for this end point

Secondary: Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)

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End point title

Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)

End point description

Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease. Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.

End point type

Secondary

End point timeframe

Day 1 (Baseline), Day 113

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	15	14	15	14	14
Units: ratio
geometric mean (confidence interval 90%)	1.08 (0.83 to 1.42)	0.69 (0.52 to 0.91)	0.82 (0.62 to 1.07)	0.84 (0.63 to 1.11)	0.62 (0.47 to 0.82)

Statistical Analysis 1

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 3000 mg Once

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0584 ^[41]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.64

Confidence interval

level

90%

sides

2-sided

lower limit

0.43

upper limit

0.94

Notes
[41] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 2

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 1500 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2274 ^[42]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.76

Confidence interval

level

90%

sides

2-sided

lower limit

0.51

upper limit

1.11

Notes
[42] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 3

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 3000 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2794 ^[43]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.77

Confidence interval

level

90%

sides

2-sided

lower limit

0.52

upper limit

1.14

Notes
[43] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 4

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 1500 mg 4 Times

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0199 ^[44]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.57

Confidence interval

level

90%

sides

2-sided

lower limit

0.39

upper limit

0.85

Notes
[44] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Secondary: Change From Baseline to Day 113 in Rheumatoid Factor (RF)

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End point title

Change From Baseline to Day 113 in Rheumatoid Factor (RF)

End point description

End point type

Secondary

End point timeframe

Day 1 (Baseline), Day 113

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	15	14	15	14	14
Units: ratio
geometric mean (confidence interval 90%)	1.20 (1.04 to 1.39)	0.77 (0.66 to 0.89)	0.74 (0.64 to 0.86)	0.72 (0.62 to 0.84)	0.57 (0.49 to 0.66)

Statistical Analysis 1

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 3000 mg Once

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0007 ^[45]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.64

Confidence interval

level

90%

sides

2-sided

lower limit

0.52

upper limit

0.79

Notes
[45] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 2

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 1500 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003 ^[46]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.62

Confidence interval

level

90%

sides

2-sided

lower limit

0.5

upper limit

0.76

Notes
[46] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 3

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 3000 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001 ^[47]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.6

Confidence interval

level

90%

sides

2-sided

lower limit

0.48

upper limit

0.74

Notes
[47] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Statistical Analysis 4

Statistical analysis description

Ratio of geometric mean is for VIB4920:placebo. Ratios less than 1 indicate a decrease.

Comparison groups

Placebo v VIB4920 1500 mg 4 Times

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[48]

Method

MMRM

Parameter type

Ratio of geometric mean versus placebo

Point estimate

0.47

Confidence interval

level

90%

sides

2-sided

lower limit

0.38

upper limit

0.59

Notes
[48] - Results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model.

Secondary: Percentage of Participants With Clinical Remission at Day 113

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End point title

Percentage of Participants With Clinical Remission at Day 113

End point description

Clinical remission is defined as DAS28-CRP < 2.6. The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.

End point type

Secondary

End point timeframe

Day 113

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	16	16	16	15	15
Units: percentage of participants
number (not applicable)	18.8	18.8	6.3	13.3	13.3

Statistical Analysis 1

Statistical analysis description

Odds ratio is VIB4920/placebo, with associated 90% CI and p-value. Odds ratios greater than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Once

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.775 ^[49]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

90%

sides

2-sided

lower limit

0.2

upper limit

Notes
[49] - Results are from logistic regression analysis with treatment and baseline DAS28-CRP score included in the model.

Statistical Analysis 2

Statistical analysis description

(Lower limit of 90% CI is < 0.1.) Odds ratio is VIB4920/placebo, with associated 90% CI and p-value. Odds ratios greater than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6974 ^[50]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.6

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

5.5

Notes
[50] - Results are from logistic regression analysis with treatment and baseline DAS28-CRP score included in the model.

Statistical Analysis 3

Statistical analysis description

Odds ratio is VIB4920/placebo, with associated 90% CI and p-value. Odds ratios greater than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9318 ^[51]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.9

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

5.7

Notes
[51] - Results are from logistic regression analysis with treatment and baseline DAS28-CRP score included in the model.

Statistical Analysis 4

Statistical analysis description

Odds ratio is VIB4920/placebo, with associated 90% CI and p-value. Odds ratios greater than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg 4 Times

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9108 ^[52]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.9

Confidence interval

level

90%

sides

2-sided

lower limit

0.2

upper limit

5.1

Notes
[52] - Results are from logistic regression analysis with treatment and baseline DAS28-CRP score included in the model.

Secondary: Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)

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End point title

Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)

End point description

Based on Kaplan-Meier method. Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants who received rescue medication.

End point type

Secondary

End point timeframe

Day 1 (Baseline) up to Day 309 (± 7 days)

End point values	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Number of subjects analysed	1 ^[53]	1 ^[54]	1 ^[55]	3 ^[56]	1 ^[57]
Units: days
median (confidence interval 90%)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (196 to 99999)

Notes
[53] - 99999=Not calculable due to small number of participants rescued.
[54] - 99999=Not calculable due to small number of participants rescued.
[55] - 99999=Not calculable due to small number of participants rescued.
[56] - 99999=Not calculable due to small number of participants rescued.
[57] - 99999=Not calculable due to small number of participants rescued.

Statistical Analysis 1

Statistical analysis description

Hazard ratio is VIB4920/placebo. Hazard ratios less than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Once

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9805 ^[58]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

10.6

Notes
[58] - Based on Cox regression method with treatment group included in the model.

Statistical Analysis 2

Statistical analysis description

Hazard ratio is VIB4920/placebo. Hazard ratios less than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9805 ^[59]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

10.6

Notes
[59] - Based on Cox regression method with treatment group included in the model.

Statistical Analysis 3

Statistical analysis description

Hazard ratio is VIB4920/placebo. Hazard ratios less than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 3000 mg Twice

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3407 ^[60]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

3.01

Confidence interval

level

90%

sides

2-sided

lower limit

0.45

upper limit

20.09

Notes
[60] - Based on Cox regression method with treatment group included in the model.

Statistical Analysis 4

Statistical analysis description

Hazard ratio is VIB4920/placebo. Hazard ratios less than 1 favor VIB4920.

Comparison groups

Placebo v VIB4920 1500 mg 4 Times

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9805 ^[61]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

90%

sides

2-sided

lower limit

0.1

upper limit

10.6

Notes
[61] - Based on Cox regression method with treatment group included in the model.

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study drug (adverse events) through through Day 309 ± 7 days.

Adverse event reporting additional description

Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo

Reporting group description

Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57

Reporting group title

VIB4920 3000 mg Once

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.

Reporting group title

VIB4920 1500 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 3000 mg Twice

Reporting group description

Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.

Reporting group title

VIB4920 1500 mg 4 Times

Reporting group description

Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57.

Serious adverse events	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 13 (0.00%)	1 / 14 (7.14%)
number of deaths (all causes)	0	0	1	0	0
number of deaths resulting from adverse events
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	VIB4920 3000 mg Once	VIB4920 1500 mg Twice	VIB4920 3000 mg Twice	VIB4920 1500 mg 4 Times
Total subjects affected by non serious adverse events
subjects affected / exposed	10 / 16 (62.50%)	10 / 18 (55.56%)	11 / 17 (64.71%)	11 / 13 (84.62%)	10 / 14 (71.43%)
Vascular disorders
Hypertension
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	1 / 13 (7.69%)	1 / 14 (7.14%)
occurrences all number	0	1	0	1	1
Surgical and medical procedures
Haemorrhoid operation
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Pyrexia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	1
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	1	0	0
Dyspnoea
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	1
Paranasal sinus inflammation
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	2 / 17 (11.76%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	1	2	1	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	2	0	0
Blood glucose abnormal
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Blood pressure increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Body temperature increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Heart sounds abnormal
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Hepatic enzyme increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Respiratory rate increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
SARS-CoV-2 antibody test positive
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Injury, poisoning and procedural complications
Chest injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Muscle strain
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Post vaccination syndrome
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Synovial rupture
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0
Cardiac disorders
Supraventricular extrasystoles
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	2	0	0
Ventricular extrasystoles
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Headache
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	1	0	0
Parkinsonian rest tremor
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Syncope
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 16 (6.25%)	2 / 18 (11.11%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	2	0	0	0
Lymphopenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	2 / 17 (11.76%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	4	0	0
Neutropenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Thrombocytopenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	2	0	0
Eye disorders
Cataract
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Hiatus hernia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Nausea
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	2	0	0
Reflux gastritis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0
Pruritus
subjects affected / exposed	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	1	0	0	0
Rosacea
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0
Leukocyturia
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	1
Back pain
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	1	0	0
Myalgia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Osteoarthritis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	3 / 13 (23.08%)	0 / 14 (0.00%)
occurrences all number	0	0	0	3	0
Osteoporosis postmenopausal
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Rheumatoid arthritis
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	3 / 17 (17.65%)	2 / 13 (15.38%)	1 / 14 (7.14%)
occurrences all number	1	0	3	4	1
Sacroiliac joint dysfunction
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Spinal osteoarthritis
subjects affected / exposed	0 / 16 (0.00%)	2 / 18 (11.11%)	2 / 17 (11.76%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	2	2	0	0
Tenosynovitis stenosans
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	1	0	0	0
COVID-19
subjects affected / exposed	1 / 16 (6.25%)	1 / 18 (5.56%)	3 / 17 (17.65%)	0 / 13 (0.00%)	3 / 14 (21.43%)
occurrences all number	1	1	3	0	3
Cystitis
subjects affected / exposed	2 / 16 (12.50%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	2	0	0	0	1
Laryngitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Nasal herpes
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	1 / 17 (5.88%)	1 / 13 (7.69%)	1 / 14 (7.14%)
occurrences all number	0	0	1	1	2
Oral candidiasis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Oral herpes
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Pharyngitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	2 / 13 (15.38%)	1 / 14 (7.14%)
occurrences all number	0	0	0	3	1
Pneumonia
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 16 (6.25%)	1 / 18 (5.56%)	0 / 17 (0.00%)	3 / 13 (23.08%)	0 / 14 (0.00%)
occurrences all number	1	1	0	3	0
Urinary tract infection
subjects affected / exposed	2 / 16 (12.50%)	0 / 18 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	5	0	1	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Hypercholesterolaemia
subjects affected / exposed	0 / 16 (0.00%)	1 / 18 (5.56%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	1	0	2	0
Hyperuricaemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 18 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0
Impaired fasting glucose
subjects affected / exposed	0 / 16 (0.00%)	0 / 18 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Oct 2019

- Removed RF isotypes from list of screening assessments. RF isotypes will be assessed during the study, but not at screening. - Removed antinuclear antibodies (ANA) from list of assessments. ANA will not be assessed during the study. - Removed anti-citrullinated protein autoantibodies (ACPA) from the autoantibody panel planned for the study assessments. ACPA will still be assessed at screening. “ACPA will be assessed with a fit-for-purpose quantitative assay (in development).” - Removed IgE from list of plasma immunoglobulins that will be assessed. - Removed “Flow cytometry (T regulatory panel” from list of study assessments and procedures.

26 Jun 2020

- Inserted lead Investigator’s name and address and clinical trial registry identifiers. - Removed the reference to Vectra DA testing in the exploratory endpoints and replaced it with “other biomarkers”; removed Vectra DA testing and replaced it with a blood sample for other biomarkers; removed the reference related to Vectra DA testing. - In Dose Preparation section, added a sentence about the required filter. - In Exclusion criterion 18, added text to require investigators to: 1) Consider the risks associated with SARS-CoV-2 circulation when assessing the suitability of a participant for enrollment, including both the participant’s epidemiologic risk and health-related risks. 2) Ensure that the participant has a documented negative SARS-CoV-2 viral test within 2 weeks prior to randomization. - Added potential risks of VIB4920 as they relate to COVID-19 or to COVID-19 vaccine response and individual participant risk factors for SARS-CoV-2 infection and for severe COVID-19 disease; added relevant references. - Added text addressing the benefit-risk of conducting this study during the potential circulation of SARS-CoV-2 and steps taken to minimize risk. - In Screening Assessments and Procedures, added a requirement for participant to have a documented negative SAR-CoV-2 viral test within 14 days of randomization. - Provided description of testing for SARS-CoV-2.

30 Sep 2020

- The circumstance under which a participant can be enrolled if methotrexate (MTX) intolerant was expanded to clarify that this includes if MTX is contraindicated. - Blood tests at screening that exclude from enrollment were changed from a prothrombin time (PT) or partial thromboplastin time (PTT) > upper limoit of normal (ULN) to > 1.2 × ULN. - Under “Repeat of screening laboratory tests”, guidance is provided to allow for some tests to be repeated within the initial screening period to assess for eligibility. - Dose Preparation: the timing between vial puncture to start of IV bag administration may not exceed 4 hours at room temperature or 24 hours at 2°C to 8°C. - The process for reporting of AESIs was clarified.

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.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Mechanistic Insight and Dosage Optimization Study of the Efficacy and Safety of VIB4920 in Patients with Rheumatoid Arthritis (RA)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline to Day 113 in DAS28-CRP

Primary: Change From Baseline to Day 113 in DAS28-CRP

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESIs)

Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events of Special Interest (TEAESIs)

Secondary: Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)

Secondary: Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)

Secondary: PK of VIB4920: Time to Cmax (Tmax)

Secondary: PK of VIB4920: Time to Cmax (Tmax)

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)

Secondary: PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)

Secondary: PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4

Secondary: PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4

Secondary: PK of VIB4920: Terminal Elimination Half-Life (t1/2)

Secondary: PK of VIB4920: Terminal Elimination Half-Life (t1/2)

Secondary: PK of VIB4920: Volume of Distribution at Steady State (Vss)

Secondary: PK of VIB4920: Volume of Distribution at Steady State (Vss)

Secondary: Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time

Secondary: Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time

Secondary: Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920

Secondary: Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920

Secondary: Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)

Secondary: Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)

Secondary: Change From Baseline to Day 113 in Rheumatoid Factor (RF)

Secondary: Change From Baseline to Day 113 in Rheumatoid Factor (RF)

Secondary: Percentage of Participants With Clinical Remission at Day 113

Secondary: Percentage of Participants With Clinical Remission at Day 113

Secondary: Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)

Secondary: Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Mechanistic Insight and Dosage Optimization Study of the Efficacy and Safety of VIB4920 in Patients with Rheumatoid Arthritis (RA)