A Phase 3, Open-label, Multicenter, Randomized Study to Evaluate the Efficacy and Safety of Romosozumab Compared with Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amgen Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

20 Nov 2023 → ongoing

Decision date (initial)

2023-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amgen Inc.

External identifiers

EU CT number

2023-503294-37-00

WHO UTN

U1111-1293-1589

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effect of romosozumab treatment for 12 months compared with bisphosphonate(s) on the number of clinical fractures at 12 months (FDA); the number of any fractures at 12 months and change in lumbar spine BMD Z-score at 12 months (EMA)

Secondary objectives 6

1. To evaluate the effect of romosozumab treatment compared with bisphosphonate(s) on changes in lumbar spine and proximal femur (total hip and femoral neck) BMD Z score at 12 months, as assessed by DXA
2. To evaluate the effect of Romosozumab treatment compared with bisphosphonate(s) on new or worsening vertebral fractures, nonvertebral fractures and long bone fractures through month 12
3. To evaluate the effect of romosozumab treatment compared with bisphosphonate(s) on change in function and pain by use of patient reported outcomes at 12-months
4. To characterize serum romosozumab concentration
5. To evaluate the effect of romosozumab treatment compared with bisphosphonate(s) on changes in lumbar spine and proximal femur (total hip and femoral neck) BMD Z score at 6 months, as assessed by DXA
6. To evaluate the effect of romosozumab treatment compared with bisphosphonate(s) on any fractures, clinical fractures, and new clinical fractures through month 12

Conditions and MedDRA coding

Osteogenesis Imperfecta

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001075-PIP04-15

Plan to share IPD

Yes

IPD plan description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Male or female subjects 5 to less than 18 years of age with a diagnosis and clinical history consistent with type I, III, or IV OI as determined by presence of expected phenotype (examples include: facial shape, voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture pattern) and lack of additional features unrelated to type I, III, or IV OI (eg, blindness, mental retardation, neuropathy, and craniosynostosis). - If familial, also must be autosomal dominant. Note: genetic testing is not required; however, if result is available, it should be consistent with type I, III, or IV.
2. Meets at least one of the following: - 3 or more fractures within the previous 2 years, or -1 or more nonvertebral fracture(s) within the previous 2 years and at least 1 prevalent vertebral fracture, or -2 or more prevalent vertebral fractures.

Exclusion criteria 4

1. History of an electrophoresis pattern inconsistent with type I, III or IV OI.
2. History of known mutation in a gene other than collagen type I alpha 1/collagen type I alpha 2 (COL1A1/COL1A2) causing OI or other metabolic bone disease.
3. History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation.
4. Use of concomitant medications that may prolong QT interval within 1 month prior to screening will be reviewed by the Principal Investigator and the Medical Monitor. Written documentation of this review is required for subject participation. Refer to Crediblemeds.org for the complete list of medications which can impact QT interval.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Number of clinical fractures (clinical vertebral fractures and nonvertebral) through Month 12
2. Number of any fractures (new and worsening vertebral compression fractures, whether clinically silent or manifest, and nonvertebral) through Month 12
3. Change from baseline in lumbar spine BMD Z-score at Month 12, as assessed by DXA

Secondary endpoints 6

1. Change from baseline in lumbar spine BMD Z score at Month 12 (this is not a secondary endpoint for the EMA as it is already listed as one of the primary endpoints)
2. Change from baseline in total hip BMD Z score at Month 12, as assessed by DXA
3. Change from baseline in femoral neck BMD Z score at Month 12, as assessed by DXA
4. •Subject incidence of nonvertebral fractures through month 12 •Subject incidence of long bone fractures through month 12 •Number of new or worsening vertebral fractures through Month 12 •Number of nonvertebral fractures through Month 12 •Number of long bone fractures through Month 12
5. Change from baseline in CHQ-PF-50 Physical Summary score, CHAQ-CV disability score and Wong-Baker Faces Pain Rating
6. Serum concentration of romosozumab at Day 1, Month 6, and Month 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amgen Inc.

Sponsor organisation

Amgen Inc.

Address

1 Amgen Center Drive

City

Thousand Oaks

Postcode

91320-1799

Country

United States

Scientific contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Public contact point

Organisation

Amgen Inc.

Contact name

Medical Information

Third parties 12

Locations

9 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 210 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications