Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the pharmacokinetics (PK) profile following multiple subcutaneous (SC) doses of romosozumab in children and adolescents with Osteogenesis Imperfecta (OI).

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

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Drug: Romosozumab
* Dietary Supplement: Calcium
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory male or female children 5 to 18 years of age 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 and lack of additional features unrelated to type I-IV OI 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 other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia) History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited cardiomyopathies, nephrotic syndrome, familial hypercholesterolemia, stroke, or any thromboembolic disorder Unhealed fracture as defined by orthopedic opinion Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation Prior treatment with anti-sclerostin antibody, fluoride or strontium, parathyroid hormone (PTH) within 12 months prior to screening, denosumab within 12 months or zoledronic acide with in 6 months prior to first dose Less than 2 evaluable vertebrae by DXA evaluation in the region of interest, L1 L4, as confirmed by the central imaging laboratory. Clinically significant valvular heart disease based on local echocardiogram (ECHO) results.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab<br> | Drug: Romosozumab<br>* Participants will receive 3 doses of romosozumab via a subcutaneous (SC) injection.<br>Dietary Supplement: Calcium<br>* All participants will receive daily supplements of elemental calcium.<br>Dietary Supplement: Vitamin D<br>* All participants will receive daily supplementation with vitamin D.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum-observed Concentration (Cmax) of Romosozumab in Serum |  | Up to Day 169 | 
| Time to Maximum-observed Concentration (tmax) of Romosozumab in Serum |  | Up to Day 169 | 
| Area Under the Curve (AUC) of Romosozumab in Serum |  | Up to Day 169 | 
| Terminal Half-life (t1/2) of Romosozumab in Serum |  | Up to Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience Treatment-emergent Adverse Events |  | Day 0 (post study drug administration) to Day 169 | 
| Number of Participants with a Clinically Significant Change from Baseline in Vital Sign Measurements |  | Baseline to Day 169 | 
| Number of Participants with Clinically Significant Changes from Baseline in Electrocardiogram (ECG) Results |  | Baseline to Day 169 | 
| Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Results |  | Baseline to Day 169 | 
| Number of Participants with Clinically Significant Changes from Baseline in Safety Laboratory Tests |  | Baseline to Day 169 | 
| Number of Participants with Antiromosuzomab Antibodies |  | Up to Day 169 | 
| Percent Change from Baseline in Bone Turnover Marker: Procollagen Type 1 N-terminal Propeptide (P1NP) |  | Baseline to Day 169 | 
| Percent Change from Baseline in Bone Turnover Marker: Serum C-telopeptide (CTX) |  | Baseline to Day 169 | 
| Percent Change from Baseline in Bone Mineral Density (BMD) at the Anteroposterior Lumbar Spine |  | Baseline to Day 169 | 
| Percent Change from Baseline in Bone Mineral Content (BMC) |  | Baseline to Day 169 | 
| Percent Change from Baseline in Bone Area |  | Baseline to Day 169 | 
| Percent Change from Baseline in Bone Mineral Density (BMD) Z-Score at Anteroposterior Lumbar Spine |  | Baseline to Day 169 |