Back to resultsStudy to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
Primary Purpose
Osteogenesis Imperfecta
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Romosozumab
Calcium
Vitamin D
Sponsored by
About this trial
This is an interventional treatment trial for Osteogenesis Imperfecta
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.
Sites / Locations
- Riley Hospital for Children
- Vanderbilt University Medical Center
- The Medical College of Wisconsin
- Kepler Universitaetsklinikum GmbH
- Uniklinik Köln
- General Children Hospital Panagioti and Aglaias Kyriakou
- Semmelweis Egyetem
- IRCCS Ospedale Pediatrico Bambino Gesu
- Hospital Sant Joan de Deu
- Hospital Universitari i Politecnic La Fe
- Hospital Universitario de Getafe
- Hospital de Cruces
- Gazi Universitesi Tip Fakultesi
- Koc Universitesi Hastanesi
- Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Romosozumab
Arm Description
Outcomes
Primary Outcome Measures
Maximum-observed Concentration (Cmax) of Romosozumab in Serum
Time to Maximum-observed Concentration (tmax) of Romosozumab in Serum
Area Under the Curve (AUC) of Romosozumab in Serum
Terminal Half-life (t1/2) of Romosozumab in Serum
Secondary Outcome Measures
Number of Participants who Experience Treatment-emergent Adverse Events
Number of Participants with a Clinically Significant Change from Baseline in Vital Sign Measurements
Number of Participants with Clinically Significant Changes from Baseline in Electrocardiogram (ECG) Results
Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Results
Number of Participants with Clinically Significant Changes from Baseline in Safety Laboratory Tests
Number of Participants with Antiromosuzomab Antibodies
Percent Change from Baseline in Bone Turnover Marker: Procollagen Type 1 N-terminal Propeptide (P1NP)
Percent Change from Baseline in Bone Turnover Marker: Serum C-telopeptide (CTX)
Percent Change from Baseline in Bone Mineral Density (BMD) at the Anteroposterior Lumbar Spine
Percent Change from Baseline in Bone Mineral Content (BMC)
Percent Change from Baseline in Bone Area
Percent Change from Baseline in Bone Mineral Density (BMD) Z-Score at Anteroposterior Lumbar Spine
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04545554
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
January 21, 2021 (Actual)
Primary Completion Date
March 30, 2023 (Actual)
Study Completion Date
March 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteogenesis Imperfecta
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Romosozumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Romosozumab
Intervention Description
Participants will receive 3 doses of romosozumab via a subcutaneous (SC) injection.
Intervention Type
Dietary Supplement
Intervention Name(s)
Calcium
Intervention Description
All participants will receive daily supplements of elemental calcium.
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D
Intervention Description
All participants will receive daily supplementation with vitamin D.
Primary Outcome Measure Information:
Title
Maximum-observed Concentration (Cmax) of Romosozumab in Serum
Time Frame
Up to Day 169
Title
Time to Maximum-observed Concentration (tmax) of Romosozumab in Serum
Time Frame
Up to Day 169
Title
Area Under the Curve (AUC) of Romosozumab in Serum
Time Frame
Up to Day 169
Title
Terminal Half-life (t1/2) of Romosozumab in Serum
Time Frame
Up to Day 169
Secondary Outcome Measure Information:
Title
Number of Participants who Experience Treatment-emergent Adverse Events
Time Frame
Day 0 (post study drug administration) to Day 169
Title
Number of Participants with a Clinically Significant Change from Baseline in Vital Sign Measurements
Time Frame
Baseline to Day 169
Title
Number of Participants with Clinically Significant Changes from Baseline in Electrocardiogram (ECG) Results
Time Frame
Baseline to Day 169
Title
Number of Participants with Clinically Significant Changes from Baseline in Physical Examination Results
Time Frame
Baseline to Day 169
Title
Number of Participants with Clinically Significant Changes from Baseline in Safety Laboratory Tests
Time Frame
Baseline to Day 169
Title
Number of Participants with Antiromosuzomab Antibodies
Time Frame
Up to Day 169
Title
Percent Change from Baseline in Bone Turnover Marker: Procollagen Type 1 N-terminal Propeptide (P1NP)
Time Frame
Baseline to Day 169
Title
Percent Change from Baseline in Bone Turnover Marker: Serum C-telopeptide (CTX)
Time Frame
Baseline to Day 169
Title
Percent Change from Baseline in Bone Mineral Density (BMD) at the Anteroposterior Lumbar Spine
Time Frame
Baseline to Day 169
Title
Percent Change from Baseline in Bone Mineral Content (BMC)
Time Frame
Baseline to Day 169
Title
Percent Change from Baseline in Bone Area
Time Frame
Baseline to Day 169
Title
Percent Change from Baseline in Bone Mineral Density (BMD) Z-Score at Anteroposterior Lumbar Spine
Time Frame
Baseline to Day 169
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-3157
Country
United States
Facility Name
The Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Kepler Universitaetsklinikum GmbH
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Uniklinik Köln
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
General Children Hospital Panagioti and Aglaias Kyriakou
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
1094
Country
Hungary
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesu
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Hospital Sant Joan de Deu
City
Esplugues de Llobregat
State/Province
Cataluña
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Facility Name
Hospital Universitario de Getafe
City
Getafe
State/Province
Madrid
ZIP/Postal Code
28905
Country
Spain
Facility Name
Hospital de Cruces
City
Baracaldo
State/Province
País Vasco
ZIP/Postal Code
48903
Country
Spain
Facility Name
Gazi Universitesi Tip Fakultesi
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Koc Universitesi Hastanesi
City
Istanbul
ZIP/Postal Code
34010
Country
Turkey
Facility Name
Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
We'll reach out to this number within 24 hrs