An Open-label, Ascending Multiple dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents with Osteogenesis Imperfecta

Phase 1

• Conditions: Osteogenesis imperfecta (OI) is a group of genetic skeletal disorders characterized by increased bone fragility, low bone mass, and increased bone turnover contributing to osteoporosis, fractures, and other conditions. OI is the most common form of primary osteoporosis in children with an estimated incidence of 1 per 25,000 live births.; MedDRA version: 20.0Level: PTClassification code 10031243Term: Osteogenesis imperfectaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2017-004972-74-IT
• Lead Sponsor: AMGEN INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-21
• Last Update Posted: 26 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

- Subject's legally acceptable representative has provided informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to initiation of any study-specific activities/procedures
- Ambulatory male or female children 5 to less than 12 years of age (cohorts 2,4, and 6) or adolescents 12 to less than 18 years of age (cohorts 1, 3 and 5) upon entry into screening
- Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI as determined by presence of expected phenotype (eg, facial shape, voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture pattern) and lack of additional features unrelated to type I-IV OI (eg, blindness, mental retardation, neuropathy, craniosynostosis, premature exfoliation of deciduous teeth)
- If familial, also must be autosomal dominant
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- History of an electrophoresis pattern inconsistent with type I to type IV OI
- History of known mutation in a gene other than collagen type I alpha/collagen type I alpha 2 (COL1AI/COL1A2) causing OI or other
metabolic bone disease
- History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation
- History of osteomalacia or rickets
- Body weight less than 10 kg or greater than 90 kg

*Please, refer to protocol for the full list

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the pharmacokinetics (PK) profile following multiple SC doses of romosozumab in children and adolescents with OI;Secondary Objective: - To evaluate the safety, tolerability, and immunogenicity profile following multiple SC doses of romosozumab in children and adolescents with OI<br>- To evaluate the pharmacodynamic (PD) profile following multiple SC doses of romosozumab in children and adolescents with OI;Primary end point(s): Romosozumab serum PK parameters: maximum-observed concentration (Cmax), time to Cmax (tmax), area under the curve (AUC) and terminal half life (t1/2);Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of<br>Assessments as per the Protocol.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Treatment-emergent adverse events, including events of injection site reactions and changes in cranial nerve function.Vital signs, electrocardiograms, physical examinations, and safety laboratory tests, including serum calcium<br>• Incidence of anti-romosozumab antibodies<br>• Bone turnover markers including serum P1NP and serum CTX measurements.<br>• Lumbar spine BMD, bone mineral content (BMC), bone area, and BMD Z-score as assessed by dual-energy X-ray absorptiometry (DXA);Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of Assessments as per the Protocol.