Download PDF

Clinical Trial Results:
An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

Summary
EudraCT number	2017-004972-74
Trial protocol	HU DE GR IT AT
Global end of trial date	30 Mar 2023

Results information
Results version number	v1(current)
This version publication date	13 Oct 2023
First version publication date	13 Oct 2023
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

20160227

ISRCTN number

US NCT number

NCT04545554

WHO universal trial number (UTN)

Sponsor organisation name

Amgen Inc.

Sponsor organisation address

One Amgen Center Drive, Thousand Oaks, CA, United States,

Public contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

Scientific contact

IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001075-PIP04-15

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?

Yes

Analysis stage

Final

Date of interim/final analysis

30 Mar 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Mar 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study is to evaluate the pharmacokinetic (PK) profile following multiple subcutaneous (SC) doses of romosozumab in children and adolescents with osteogenesis imperfecta.

Protection of trial subjects

The study was conducted in accordance with International Council for Harmonisation Good Clinical Practice and other regulations/guidelines. The investigator or his/her designee informed the participant of all aspects pertaining to the participant's participation in the study before any screening procedures were performed. The study protocol and all amendments, the informed consent form, and any accompanying materials provided to the participants were reviewed and approved by an Institutional Review Board or Institutional Ethics Committee at each study center.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Jan 2021

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 1

Country: Number of subjects enrolled

Hungary: 9

Country: Number of subjects enrolled

Turkey: 7

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Greece: 3

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Spain: 3

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

Top of page

Recruitment details

Participants were enrolled at 15 study centers in Austria, Germany, Greece, Hungary, Italy, Spain, Turkey, and the United States, and participated from 21 January 2021 until 30 March 2023.

Screening details

Ambulatory children (5 to < 12 years of age) and adolescents (12 to < 18 years of age) with osteogenesis imperfecta were enrolled to receive 1 of 3 SC dose levels of romosozumab. Specific doses are blinded due to the protection of propriety information.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose A was administered SC.

Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose A was administered SC.

Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose B was administered SC.

Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose B was administered SC.

Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose C was administered SC.

Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)

Arm description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Arm type

Experimental

Investigational medicinal product name

Romosozumab

Investigational medicinal product code

Other name

Evenity®

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Romosozumab Dose C was administered SC.

Number of subjects in period 1	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Started	4	4	4	5	4	4
Received at least 1 dose romosozumab	4	4	4	5	4	4
Received all doses of romosozumab	4	4	4	4	4	4
Completed	4	4	4	4	4	4
Not completed	0	0	0	1	0	0
Consent withdrawn by subject	-	-	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Reporting group title

Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Reporting group values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)	Total
Number of subjects	4	4	4	5	4	4	25
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0
Children (2-11 years)	0	4	0	5	0	4	13
Adolescents (12-17 years)	4	0	4	0	4	0	12
Adults (18-64 years)	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	14.3 ± 1.9	6.0 ± 1.4	14.3 ± 0.5	8.4 ± 2.4	14.0 ± 1.8	6.5 ± 0.6	-
Sex: Female, Male
Units: participants
Female	1	0	1	4	2	1	9
Male	3	4	3	1	2	3	16
Race/Ethnicity, Customized
Units: Subjects
Asian	0	0	0	0	0	1	1
White	4	4	4	4	4	2	22
Other	0	0	0	1	0	1	2
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	2	1	0	3
Not Hispanic or Latino	4	4	4	3	3	4	22
Unknown or Not Reported	0	0	0	0	0	0	0

End points

Top of page

Reporting group title

Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Reporting group title

Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Primary: Maximum Observed Serum Concentration (Cmax) of Romosozumab

Top of page

End point title

Maximum Observed Serum Concentration (Cmax) of Romosozumab ^[1]

End point description

Mean Cmax values following single and multiple SC administrations of romosozumab are presented. Pharmacokinetic (PK) Analysis Set: all participants for whom at least 1 PK parameter or endpoint could be adequately tested.

End point type

Primary

End point timeframe

Day 1 to Day 169

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: No comparative statistical analysis was planned for this endpoint; summary statistics were provided for the primary endpoint.

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	4	4	4
Units: μg/mL
arithmetic mean (standard deviation)
Single Dose	2.64 ± 1.06	1.74 ± 0.825	13.8 ± 6.32	10.3 ± 1.70	25.7 ± 3.02	21.3 ± 6.45
Multiple Doses	2.43 ± 1.36	5.55 ± 2.11	12.8 ± 6.31	9.14 ± 7.50	22.8 ± 10.5	19.4 ± 2.14

No statistical analyses for this end point

Primary: Time to Cmax (tmax) of Romosozumab

Top of page

End point title

Time to Cmax (tmax) of Romosozumab ^[2]

End point description

Median tmax values following single and multiple SC administrations of romosozumab are presented. PK Analysis Set: all participants for whom at least 1 PK parameter or endpoint could be adequately tested.

End point type

Primary

End point timeframe

Day 1 to Day 169

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: No comparative statistical analysis was planned for this endpoint; summary statistics were provided for the primary endpoint.

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	4	4	4
Units: day
median (full range (min-max))
Single Dose	6.5 (5.9 to 7.9)	7.9 (7.9 to 15)	6.9 (6.9 to 7.0)	6.9 (4.9 to 7.1)	7.0 (4.9 to 8.0)	7.5 (6.9 to 8.9)
Multiple Doses	7.0 (7.0 to 12)	7.0 (6.9 to 7.0)	7.0 (6.0 to 7.9)	8.0 (6.0 to 11)	7.0 (4.0 to 12)	7.5 (6.0 to 8.8)

No statistical analyses for this end point

Primary: Area Under the Serum Concentration Time Curve (AUC) During the Dosing Interval (AUCtau) of Romosozumab

Top of page

End point title

Area Under the Serum Concentration Time Curve (AUC) During the Dosing Interval (AUCtau) of Romosozumab ^[3]

End point description

Mean AUCtau values following single and multiple SC administrations of romosozumab are presented. PK Analysis Set: all participants for whom at least 1 PK parameter or endpoint could be adequately tested.

End point type

Primary

End point timeframe

Day 1 to Day 85

Notes
[3] - 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: No comparative statistical analysis was planned for this endpoint; summary statistics were provided for the primary endpoint.

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	4	4	4
Units: day*μg/mL
arithmetic mean (standard deviation)
Single Dose	30.9 ± 13.5	16.9 ± 5.78	163 ± 89.1	113 ± 50.3	344 ± 106	234 ± 93.7
Multiple Doses	27.4 ± 15.1	50.5 ± 20.7	153 ± 86.7	95.1 ± 76.1	293 ± 134	203 ± 40.7

No statistical analyses for this end point

Primary: Accumulation Ratio of Romosozumab

Top of page

End point title

Accumulation Ratio of Romosozumab ^[4]

End point description

The accumulation ratio was calculated as AUCtau after multiple doses/AUCtau Dose 1. PK Analysis Set: all participants for whom at least 1 PK parameter or endpoint could be adequately tested.

End point type

Primary

End point timeframe

Day 1 to Day 85

Notes
[4] - 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: No comparative statistical analysis was planned for this endpoint; summary statistics were provided for the primary endpoint.

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	4	4	4
Units: ratio
arithmetic mean (standard deviation)	0.885 ± 0.487	3.6 ± 2.56	0.922 ± 0.0673	0.724 ± 0.392	0.843 ± 0.260	0.935 ± 0.283

No statistical analyses for this end point

Primary: Terminal Half-life of Romosozumab

Top of page

End point title

Terminal Half-life of Romosozumab ^[5]

End point description

Median terminal half-life values following multiple SC administrations of romosozumab are presented. PK Analysis Set: all participants for whom at least 1 PK parameter or endpoint could be adequately tested. Data is presented for participants with evaluable data. 99999 = data is not available.

End point type

Primary

End point timeframe

Day 1 to Day 169

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: No comparative statistical analysis was planned for this endpoint; summary statistics were provided for the primary endpoint.

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	0 ^[6]	2	0 ^[7]	1	3	0 ^[8]
Units: day
median (full range (min-max))	( to )	9.41 (7.62 to 11.2)	( to )	7.01 (7.01 to 7.01)	6.11 (5.58 to 6.56)	( to )

Notes
[6] - No participants were evaluated in Cohort 1 for this endpoint.
[7] - No participants were evaluated in Cohort 3 for this endpoint.
[8] - No participants were evaluated in Cohort 6 for this endpoint.

No statistical analyses for this end point

Secondary: Number of Participants with Changes from Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

Top of page

End point title

Number of Participants with Changes from Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

End point description

Facial nerve (cranial nerve VII) function was assessed clinically by facial symmetry inspection at rest, followed by assessment of the symmetry of specific facial movements: raising eyebrows, closing the eyes, blowing out the cheeks, smiling, pursing and closing the lips. Results of the cranial nerve examination were classed as 0 = Normal; 1 = Abnormal not clinically significant; and 2 = Abnormal clinically significant. An increase from baseline indicates an increase in abnormal clinical findings on the cranial nerve VII examination. Safety Analysis Set: all participants enrolled in the study who received at least 1 dose of investigational product. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

Baseline (Day 1), Day 57, Day 85, and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: participants
Day 57: Blowing out of cheeks - No change (0)	4	4	4	3	4	4
Day 57: Blowing out of cheeks - Undetermined	0	0	0	2	0	0
Day 57: Closing eyes - No change (0)	4	4	4	3	4	4
Day 57: Closing eyes - Undetermined	0	0	0	2	0	0
Day 57: Closing of lips - No change (0)	4	4	4	3	4	4
Day 57: Closing of lips - Undetermined	0	0	0	2	0	0
Day 57: Pursing of lips - No change (0)	4	4	4	3	4	4
Day 57: Pursing of lips - Undetermined	0	0	0	2	0	0
Day 57: Raising eyebrows - No change (0)	4	4	4	3	4	4
Day 57: Raising eyebrows - Undetermined	0	0	0	2	0	0
Day 57: Smiling - No change (0)	4	4	4	3	4	4
Day 57: Smiling - Undetermined	0	0	0	2	0	0
Day 85: Blowing out of cheeks - No change (0)	4	4	4	4	4	4
Day 85: Blowing out of cheeks - Undetermined	0	0	0	1	0	0
Day 85: Closing eyes - No change (0)	4	4	4	4	4	4
Day 85: Closing eyes - Undetermined	0	0	0	1	0	0
Day 85: Closing of lips - No change (0)	4	3	4	4	4	4
Day 85: Closing of lips - Increase (to 1)	0	1	0	0	0	0
Day 85: Closing of lips - Undetermined	0	0	0	1	0	0
Day 85: Pursing of lips - No change (0)	4	4	4	4	4	4
Day 85: Pursing of lips - Undetermined	0	0	0	1	0	0
Day 85: Raising eyebrows - No change (0)	4	4	4	4	4	4
Day 85: Raising eyebrows - Undetermined	0	0	0	1	0	0
Day 85: Smiling - No change (0)	4	4	4	4	4	4
Day 85: Smiling - Undetermined	0	0	0	1	0	0
Day 169: Blowing out of cheeks - No change (0)	4	4	4	4	4	4
Day 169: Blowing out of cheeks - Undetermined	0	0	0	1	0	0
Day 169: Closing eyes - No change (0)	4	4	4	4	4	4
Day 169: Closing eyes - Undetermined	0	0	0	1	0	0
Day 169: Closing of lips - No change (0)	4	4	4	4	4	4
Day 169: Closing of lips - Undetermined	0	0	0	1	0	0
Day 169: Pursing of lips - No change (0)	4	4	4	4	4	4
Day 169: Pursing of lips - Undetermined	0	0	0	1	0	0
Day 169: Raising eyebrows - No change (0)	4	4	4	4	4	4
Day 169: Raising eyebrows - Undetermined	0	0	0	1	0	0
Day 169: Smiling - No change (0)	4	4	4	4	4	4
Day 169: Smiling - Undetermined	0	0	0	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Top of page

End point title

Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

End point description

TEAEs were adverse events (AEs) that started on or after first dose of investigational product up to the end of study (up to Day 169). Any clinically significant changes in vital signs, electrocardiogram parameters, physical exam findings, and clinical laboratory parameters were reported as TEAEs. Injection site reactions were events of interest (EOI) for this study. Safety Analysis Set: all participants enrolled in the study who received at least 1 dose of investigational product.

End point type

Secondary

End point timeframe

Day 1 to end of study (up to Day 169); median duration on study was 5.55 months

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: participants
Any TEAE	1	1	2	4	1	3
Any Treatment-emergent EOI	0	0	0	0	1	1

No statistical analyses for this end point

Secondary: Number of Participants with Anti-romosozumab Antibodies

Top of page

End point title

Number of Participants with Anti-romosozumab Antibodies

End point description

Treatment-boosted anti-romosozumab antibody was defined as binding antibody positive at baseline with a >4 x increase in magnitude post-baseline. Transient results were defined as negative results at the participant's last time point tested within the study period. Safety Analysis Set: all participants enrolled in the study who received at least 1 dose of investigational product. Ab - antibody; NAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline; tran = transient

End point type

Secondary

End point timeframe

Blood samples for anti-romosozumab antibodies were taken Day 1 (baseline), Day 15, Day 29, Day 85, and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: participants
Binding Ab +ve anytime	0	1	2	0	1	1
NAb +ve anytime	0	0	2	0	1	0
Binding Ab +ve at/before BL	0	0	0	0	0	0
NAb +ve at/before baseline	0	0	0	0	0	0
Treatment boosted Ab +ve	0	0	0	0	0	0
Binding Ab +ve post-BL with -ve/no results at BL	0	1	2	0	1	1
Tran binding Ab +ve post-BL with -ve/no results BL	0	0	0	0	0	0
NAb +ve post-BL with -ve/no result at BL	0	0	2	0	1	0
Tran NAb +ve post-BL with -ve/no result BL	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage Change from Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

Top of page

End point title

Percentage Change from Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

End point description

Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points. PD Analysis Set: all participants for whom at least 1 PD parameter or endpoint could be adequately estimated. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

Blood samples were taken Day 1 (baseline), Day 8, Day 15, Day 29, Day 57, Days 64, 71, 85, 113, and 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: percentage change
arithmetic mean (standard deviation)
Day 8 (N=4,3,4,5,4,4)	2.65 ± 27.91	-19.93 ± 33.97	8.79 ± 19.21	-19.38 ± 20.01	-12.33 ± 12.93	7.14 ± 29.89
Day 15 (N=3,4,4,4,4,3)	12.26 ± 28.20	-3.24 ± 41.30	-2.14 ± 52.91	-20.24 ± 21.12	-17.22 ± 17.39	42.62 ± 54.95
Day 29 (N=4,4,4,4,4,4)	-4.67 ± 21.35	-6.67 ± 39.99	26.00 ± 15.11	-7.43 ± 18.63	-16.09 ± 27.05	3.76 ± 24.72
Day 57 (N=4,4,4,4,4,4)	1.03 ± 34.14	-7.34 ± 25.32	-0.32 ± 32.21	-7.66 ± 13.16	-1.40 ± 38.10	44.17 ± 95.30
Day 64 (N=3,4,4,3,3,2)	-13.37 ± 36.33	-18.26 ± 49.19	19.91 ± 43.95	-10.60 ± 36.12	10.95 ± 23.38	-28.14 ± 11.51
Day 71 (N=4,4,4,3,4,4)	18.20 ± 53.85	-25.30 ± 50.43	35.26 ± 68.16	-3.37 ± 8.25	15.14 ± 51.39	60.12 ± 106.28
Day 85 (N=4,4,4,4,4,4)	-10.56 ± 22.18	-37.50 ± 14.12	9.95 ± 30.71	5.08 ± 24.34	0.71 ± 44.55	15.77 ± 58.40
Day 113 (N=4,4,4,4,4,4)	-3.83 ± 22.30	-30.38 ± 19.59	25.94 ± 39.76	6.98 ± 37.98	7.03 ± 40.23	-19.58 ± 10.98
Day 169 (N=4,4,4,4,4,4)	-6.15 ± 54.87	-29.78 ± 31.60	-1.72 ± 40.42	11.08 ± 16.19	-8.07 ± 16.73	8.08 ± 49.45

No statistical analyses for this end point

Secondary: Percentage Change from Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

Top of page

End point title

Percentage Change from Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

End point description

Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points. PD Analysis Set: all participants for whom at least 1 PD parameter or endpoint could be adequately estimated. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

Blood samples were taken Day 1 (baseline), Day 8, Day 15, Day 29, Day 57, Days 64, 71, 85, 113, and 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: percentage change
arithmetic mean (standard deviation)
Day 8 (N=4,3,4,5,4,4)	19.81 ± 20.96	12.75 ± 13.03	65.12 ± 17.75	31.77 ± 11.69	35.91 ± 21.89	35.35 ± 47.08
Day 15 (N=3,4,4,4,4,3)	11.03 ± 13.94	12.43 ± 13.07	52.25 ± 29.71	10.52 ± 14.72	58.58 ± 54.61	28.35 ± 55.00
Day 29 (N=4,4,4,4,4,4)	5.24 ± 12.87	6.18 ± 18.64	21.52 ± 25.01	1.96 ± 9.22	32.13 ± 59.10	-11.54 ± 11.35
Day 57 (N=4,4,4,4,4,4)	-2.11 ± 20.26	-22.37 ± 19.82	14.57 ± 36.09	-6.36 ± 17.51	19.07 ± 56.24	-14.26 ± 12.93
Day 64 (N=3,4,4,3,3,4)	14.82 ± 28.86	19.12 ± 40.48	39.63 ± 31.92	25.42 ± 16.73	77.17 ± 109.07	17.51 ± 35.74
Day 71 (N=4,4,4,3,4,4)	12.19 ± 21.37	-5.72 ± 28.50	49.37 ± 37.99	16.79 ± 12.29	42.16 ± 59.39	5.12 ± 29.54
Day 85 (N=4,4,4,4,4,4)	-7.34 ± 22.50	-23.50 ± 13.42	26.12 ± 48.97	-0.72 ± 21.29	5.79 ± 23.45	-11.78 ± 30.09
Day 113 (N=4,4,4,4,4,4)	-1.13 ± 13.42	-13.75 ± 19.11	21.10 ± 40.61	2.53 ± 42.46	-5.02 ± 21.00	-26.95 ± 10.23
Day 169 (N=4,4,4,4,4,4)	-6.62 ± 30.96	-3.13 ± 10.54	18.10 ± 57.53	-2.24 ± 23.99	-14.30 ± 19.41	-21.85 ± 16.18

No statistical analyses for this end point

Secondary: Percentage Change from Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

Top of page

End point title

Percentage Change from Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

End point description

BMD was assessed by dual energy X-ray absorptiometry (DXA) scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA. The BMD Analysis Set: all participants who have a baseline lumbar spine DXA BMD measurement and at least 1 post-baseline lumbar spine DXA BMD measurement. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

DXA scans were during screening (baseline) and at Day 85 and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: percentage change
arithmetic mean (standard deviation)
Day 85 (N=4,4,4,4,4,4)	4.84 ± 3.29	7.94 ± 5.32	12.91 ± 2.60	7.78 ± 9.16	7.88 ± 1.99	13.07 ± 13.45
Day 169 (N=4,4,4,4,4,4)	7.80 ± 2.23	9.24 ± 7.98	15.04 ± 4.32	7.09 ± 7.03	7.10 ± 6.58	12.70 ± 12.86

No statistical analyses for this end point

Secondary: Percentage Change from Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

Top of page

End point title

Percentage Change from Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

End point description

BMC was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA. The BMD Analysis Set: all participants who have a baseline lumbar spine DXA BMD measurement and at least 1 post-baseline lumbar spine DXA BMD measurement. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

DXA scans were during screening (baseline) and at Day 85 and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: percentage change
arithmetic mean (standard deviation)
Day 85 (N=4,4,4,4,4,4)	7.68 ± 8.10	10.13 ± 6.05	18.16 ± 7.86	8.41 ± 6.90	14.62 ± 3.39	16.03 ± 8.32
Day 169 (N=4,4,4,4,4,4)	12.64 ± 4.07	11.40 ± 7.82	21.29 ± 11.31	7.98 ± 7.77	14.27 ± 5.52	12.42 ± 10.72

No statistical analyses for this end point

Secondary: Percentage Change from Baseline in Lumbar Spine Bone Area

Top of page

End point title

Percentage Change from Baseline in Lumbar Spine Bone Area

End point description

Bone area was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA. The BMD Analysis Set: all participants who have a baseline lumbar spine DXA BMD measurement and at least 1 post-baseline lumbar spine DXA BMD measurement. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

DXA scans were during screening (baseline) and at Day 85 and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: percentage change
arithmetic mean (standard deviation)
Day 85 (N=4,4,4,4,4,4)	2.72 ± 6.99	2.03 ± 1.62	4.60 ± 5.00	0.80 ± 4.62	6.23 ± 2.15	3.44 ± 11.05
Day 169 (N=4,4,4,4,4,4)	4.53 ± 4.92	1.92 ± 0.66	5.30 ± 6.06	0.82 ± 1.95	6.87 ± 5.14	-0.09 ± 4.27

No statistical analyses for this end point

Secondary: Mean Change from Baseline in Lumbar Spine BMD Z-Score

Top of page

End point title

Mean Change from Baseline in Lumbar Spine BMD Z-Score

End point description

Lumbar spine BMD was assessed by DXA scans. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from baseline indicated an improvement in lumbar spine BMD. The BMD Analysis Set: all participants who have a baseline lumbar spine DXA BMD measurement and at least 1 post-baseline lumbar spine DXA BMD measurement. Participants with data available at each time point are presented.

End point type

Secondary

End point timeframe

DXA scans were during screening (baseline) and at Day 85 and Day 169

End point values	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Number of subjects analysed	4	4	4	5	4	4
Units: Z-score
arithmetic mean (standard deviation)
Day 85 (N=4,3,4,4,4,4)	0.20 ± 0.39	0.45 ± 0.37	0.50 ± 0.12	0.33 ± 0.53	0.33 ± 0.26	0.53 ± 0.79
Day 169 (N=4,4,4,4,4,4)	0.33 ± 0.46	0.48 ± 0.51	0.48 ± 0.21	0.25 ± 0.39	0.23 ± 0.56	0.50 ± 0.62

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were collected from first dose of study drug to the end of study visit (up to Day 169); median duration of treatment was 5.55 months.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose A (low dose).

Reporting group title

Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose B (medium dose).

Reporting group title

Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Reporting group title

Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)

Reporting group description

Participants received multiple SC doses of romosozumab Dose C (high dose).

Serious adverse events	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Lower limb fracture
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0

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

Non-serious adverse events	Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)	Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)	Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)	Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)	Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)	Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	4 / 5 (80.00%)	1 / 4 (25.00%)	3 / 4 (75.00%)
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Ankle fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0
Femur fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1
Tooth fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Neck injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	0	0	0	3
General disorders and administration site conditions
Injection site swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1	1
Injection site erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1	2
Injection site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	2
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	1
Eye disorders
Ocular hyperaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0
Abnormal faeces
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Toothache
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0
Haematochezia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0	0
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Catarrh
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	3	0	0
Increased upper airway secretion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	0	0	0	4
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	3	0	1
Back pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0	0
Muscle contracture
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0
Muscle swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	0	1	0	3
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	0	0	0	2
Nasopharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	0	3
COVID-19
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Apr 2020

- The placebo group was removed from the study. - Increased number of participants with active treatment from 3 to 4 for better understanding of PK variability at each dose level. - Hip DXA was removed. - BMD, BMC, and bone area were added as DXA parameters in the secondary endpoints. - ECG assessment was added on Day 29. - Serum PK collection was added to Day 169 and removed from Day 61. Anti-drug antibody collection was added to Day 15. - Pregnancy testing at screening was to be done using serum samples, but all other pregnancy assessments remained unchanged using urine samples. - Exclusion criteria were updated to exclude participants with body weight < 10 kg and > 90 kg; to add conditions associated with increased risk of cardiovascular disease; to clarify that removal of baby teeth was not considered an invasive dental procedure; to exclude participants within 12 months of prior denosumab used. - Common Terminology Criteria for Adverse Events grading scale was replaced with the Amgen Standard Grading Scale as it was more appropriate for the study design and population. - Tanner staging was removed. A history of menarche was to be solely used to determine whether female participants would undergo pregnancy testing. - Adjudication of atypical femoral fractures and potential cardiovascular events was removed. - Disease-related events were removed from the protocol to align with Amgen's current processes for reporting adverse events. The anticipated serious adverse event definition was removed because all serious adverse events were to be reported to health authorities in an expedited manner.

26 May 2020

- Updated participant screening number assignment to using interactive response technology.

19 Feb 2021

- Updated Schedule of Assessments table and protocol to include visits 2 hours post-dose and removed Day 61 visit; updated to include information about home care services and assessments that could be performed at home; and updated alcohol and drug testing and ECG, telephonic safety assessments at screening visits. - Updated study design to include the participant monitoring details for 2 hours after the first and subsequent dosing of romosozumab. - Pediatric risk assessment language was updated to include risk of valvular heart disease and safety monitoring to include neurological assessments; and to add details of potential COVID-19 risks. - Study rationale was updated to include details of romosozumab PK model for children. - Exclusion criteria were updated to include clinically significant valvular heart disease. - Added details regarding drug substances of abuse along with alcohol and tobacco restrictions. - Updated the contraceptive requirements to include progesterone-only hormonal contraception language and removed two-barrier methods. - Updated the text to include adverse event reporting after signing the informed consent form through to end of study. - Removed language for the worldwide reporting regulations for all adverse events unblinding from reporting procedures for serious adverse events. - Included the BMD analysis set. - Remove 'by treatment group' for statistical considerations.

28 Feb 2023

- Corrected text regarding laboratory assessments to be completed by the central laboratory as the Schedule of Assessments erroneously listed them to be completed by the local laboratory.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maximum Observed Serum Concentration (Cmax) of Romosozumab

Primary: Maximum Observed Serum Concentration (Cmax) of Romosozumab

Primary: Time to Cmax (tmax) of Romosozumab

Primary: Time to Cmax (tmax) of Romosozumab

Primary: Area Under the Serum Concentration Time Curve (AUC) During the Dosing Interval (AUCtau) of Romosozumab

Primary: Area Under the Serum Concentration Time Curve (AUC) During the Dosing Interval (AUCtau) of Romosozumab

Primary: Accumulation Ratio of Romosozumab

Primary: Accumulation Ratio of Romosozumab

Primary: Terminal Half-life of Romosozumab

Primary: Terminal Half-life of Romosozumab

Secondary: Number of Participants with Changes from Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

Secondary: Number of Participants with Changes from Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

Secondary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary: Number of Participants with Anti-romosozumab Antibodies

Secondary: Number of Participants with Anti-romosozumab Antibodies

Secondary: Percentage Change from Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

Secondary: Percentage Change from Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

Secondary: Percentage Change from Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

Secondary: Percentage Change from Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

Secondary: Percentage Change from Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

Secondary: Percentage Change from Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

Secondary: Percentage Change from Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

Secondary: Percentage Change from Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

Secondary: Percentage Change from Baseline in Lumbar Spine Bone Area

Secondary: Percentage Change from Baseline in Lumbar Spine Bone Area

Secondary: Mean Change from Baseline in Lumbar Spine BMD Z-Score

Secondary: Mean Change from Baseline in Lumbar Spine BMD Z-Score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta