Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

• ClinicalTrials.gov Identifier: NCT04545554
• Recruitment Status: Active, not recruiting
• First Posted: September 11, 2020
• Last Update Posted: December 8, 2022
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: September 4, 2020
• First Posted Date: September 11, 2020
• Last Update Posted Date: December 8, 2022
• Actual Study Start Date: January 21, 2021
• Estimated Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 4, 2020)

• Maximum-observed Concentration (Cmax) of Romosozumab in Serum [ Time Frame: Up to Day 169 ]
• Time to Maximum-observed Concentration (tmax) of Romosozumab in Serum [ Time Frame: Up to Day 169 ]
• Area Under the Curve (AUC) of Romosozumab in Serum [ Time Frame: Up to Day 169 ]
• Terminal Half-life (t1/2) of Romosozumab in Serum [ Time Frame: Up to Day 169 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 4, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
• Official Title: An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Osteogenesis Imperfecta

Intervention

• Drug: Romosozumab
  Participants will receive 3 doses of romosozumab via a subcutaneous (SC) injection.
• Dietary Supplement: Calcium
  All participants will receive daily supplements of elemental calcium.
• Dietary Supplement: Vitamin D
  All participants will receive daily supplementation with vitamin D.

Study Arms

Experimental: Romosozumab

Interventions:

• Drug: Romosozumab
• Dietary Supplement: Calcium
• Dietary Supplement: Vitamin D

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 22, 2022): 25
• Original Estimated Enrollment (submitted: September 4, 2020): 16
• Estimated Study Completion Date: March 30, 2023
• Estimated Primary Completion Date: March 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Germany, Greece, Hungary, Italy, Spain, Turkey, United States

Administrative Information

• NCT Number: NCT04545554
• Other Study ID Numbers: 20160227; 2017-004972-74 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: December 2022