Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

NCT04545554 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 201602272017-004972-74
• Study Type: interventional
• Target: 25
• Locations: 8 countries
• Sites: 15

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).

Conditions

Osteogenesis Imperfecta

Outcome Measures

Primary Outcomes (5)

• Maximum Observed Serum Concentration (Cmax) of Romosozumab

  Mean Cmax values following Days 1 and 57 are presented.

  Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57

• Time to Cmax (Tmax) of Romosozumab

  Median tmax values following Days 1 and 57 are presented.

  Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57

• Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab

  Mean AUC(0-28) values following Days 1 and 57 are presented.

  Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57

• Accumulation Ratio of Romosozumab

  The accumulation ratio was calculated as AUC(0-28) at Day 57/AUC(0-28) at Day 1. Mean accumulation ratio values based on analysis at Days 1 and 57 are presented, as pre-specified.

  Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57

• Terminal Half-life of Romosozumab

  Median terminal half-life values at Day 57 are presented.

  Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Day 57

Secondary Outcomes (9)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Day 1 to end of study (up to Day 169); median duration on study was 5.55 months

• Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

  Baseline (Day 1), Day 57, Day 85, and Day 169

• Number of Participants With Anti-romosozumab Antibodies

  Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169

• Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

  Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169

• Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

  Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169

Study Arms (2)

Romosozumab: 12 - < 18 Years of Age

EXPERIMENTAL

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

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

Romosozumab: 5 - < 12 Years of Age

EXPERIMENTAL

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

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

Interventions

Romosozumab DRUG

Participants will receive multiple doses of romosozumab via a SC injection.

Romosozumab: 12 - < 18 Years of Age; Romosozumab: 5 - < 12 Years of Age

Calcium DIETARY_SUPPLEMENT

All participants will receive daily supplements of elemental calcium.

Romosozumab: 12 - < 18 Years of Age; Romosozumab: 5 - < 12 Years of Age

Vitamin D DIETARY_SUPPLEMENT

All participants will receive daily supplementation with vitamin D.

Romosozumab: 12 - < 18 Years of Age; Romosozumab: 5 - < 12 Years of Age

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (15)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212-3157, United States

Location

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Kepler Universitaetsklinikum GmbH

Linz, 4020, Austria

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

General Children Hospital Panagioti and Aglaias Kyriakou

Athens, 11527, Greece

Location

Semmelweis Egyetem

Budapest, 1094, Hungary

Location

IRCCS Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Hospital de Cruces

Barakaldo, Basque Country, 48903, Spain

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Catalonia, 08950, Spain

Location

Hospital Universitario de Getafe

Getafe, Madrid, 28905, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, 46026, Spain

Location

Gazi Universitesi Tip Fakultesi

Ankara, 06500, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi

Istanbul, 34010, Turkey (Türkiye)

Location

Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (1)

• Tabaie SA, O'Mara AE, Sheppard ED, Tosi LL. A Comprehensive Review of Bone Health in a Child: From Birth to Adulthood. J Am Acad Orthop Surg. 2024 May 1;32(9):363-372. doi: 10.5435/JAAOS-D-23-00853. Epub 2024 Jan 23.

  PMID: 38261781 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

romosozumab; Calcium; Vitamin D

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 11, 2020
• Study Start: January 21, 2021
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: April 15, 2024
• Results First Posted: April 15, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

AU (1); ES (4); HU (1); GR (1); DE (1); TU (3); US (3); IT (1)