Phase 1
N=25
Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
Osteogenesis Imperfecta
Bottom Line
View on ClinicalTrials.gov: NCT04545554 ↗Enrolled (actual)
25
Serious AEs
8.0%
Results posted
Apr 2024
Primary outcome: Primary: Maximum Observed Serum Concentration (Cmax) of Romosozumab — 2.64; 1.74; 13.8; 10.3 μg/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Romosozumab (Drug); Calcium (Dietary_supplement); Vitamin D (Dietary_supplement)
- Age
- Pediatric · 5+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Mar 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Serum Concentration (Cmax) of Romosozumab |
2.64; 1.74; 13.8; 10.3; 25.7; 21.3 | — |
| PRIMARY Time to Cmax (Tmax) of Romosozumab |
6.5; 7.9; 6.9; 6.9; 7.0; 7.5 | — |
| PRIMARY Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab |
30.9; 16.9; 163; 113; 344; 234 | — |
| PRIMARY Accumulation Ratio of Romosozumab |
0.885; 3.6; 0.922; 0.724; 0.843; 0.935 | — |
| PRIMARY Terminal Half-life of Romosozumab |
9.41; 7.01; 6.11 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
1; 1; 2; 4; 1; 3 | — |
| SECONDARY Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169 |
4; 4; 4; 3; 4; 4 | — |
| SECONDARY Number of Participants With Anti-romosozumab Antibodies |
0; 1; 2; 0; 1; 1 | — |
| SECONDARY Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX) |
2.65; -19.93; 8.79; -19.38; -12.33; 7.14 | — |
| SECONDARY Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP) |
19.81; 12.75; 65.12; 31.77; 35.91; 35.35 | — |
| SECONDARY Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine |
4.84; 7.94; 12.91; 7.78; 7.88; 13.07 | — |
| SECONDARY Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine |
7.68; 10.13; 18.16; 8.41; 14.62; 16.03 | — |
| SECONDARY Percentage Change From Baseline in Lumbar Spine Bone Area |
2.72; 2.03; 4.60; 0.80; 6.23; 3.44 | — |
| SECONDARY Mean Change From Baseline in Lumbar Spine BMD Z-Score |
0.20; 0.45; 0.50; 0.33; 0.33; 0.53 | — |
Summary
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).
Eligibility Criteria
Inclusion Criteria
- Ambulatory male or female children 5 to less than 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 1/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 acid within 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.
Data sourced from ClinicalTrials.gov (NCT04545554). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.