Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

Amgen

Status and phase: Completed; Phase 1

Conditions: Osteogenesis Imperfecta

Treatments: Dietary Supplement: Vitamin D; Drug: Romosozumab; Dietary Supplement: Calcium

Study type: Interventional

Funder types: Industry

Identifiers

NCT04545554

20160227

2017-004972-74 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 25 patients

Sex: All

Ages: 5 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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25 participants in 2 patient groups

Romosozumab: 12 - < 18 Years of Age

Experimental group

Description:

Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.

Treatment:

Drug: Romosozumab

Dietary Supplement: Calcium

Dietary Supplement: Vitamin D

Romosozumab: 5 - < 12 Years of Age

Experimental group

Description:

Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.

Treatment:

Drug: Romosozumab

Dietary Supplement: Calcium

Dietary Supplement: Vitamin D