Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

October 18, 2023 updated by: Amgen

An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Linz, Austria, 4020
        • Kepler Universitaetsklinikum GmbH
  • Germany
      • Koeln, Germany, 50937
        • Uniklinik Koln
  • Greece
      • Athens, Greece, 11527
        • General Children Hospital Panagioti and Aglaias Kyriakou
  • Hungary
      • Budapest, Hungary, 1094
        • Semmelweis Egyetem
  • Italy
      • Roma, Italy, 00165
        • IRCCS Ospedale Pediatrico Bambino Gesu
  • Spain
    • Cataluña
      • Esplugues de Llobregat, Cataluña, Spain, 08950
        • Hospital Sant Joan de Déu
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
    • Madrid
      • Getafe, Madrid, Spain, 28905
        • Hospital Universitario de Getafe
    • País Vasco
      • Baracaldo, País Vasco, Spain, 48903
        • Hospital de Cruces
  • Turkey
      • Ankara, Turkey, 06500
        • Gazi Universitesi Tip Fakultesi
      • Istanbul, Turkey, 34010
        • Koç Üniversitesi Hastanesi
      • Izmir, Turkey, 35100
        • Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Tennessee
      • Nashville, Tennessee, United States, 37212-3157
        • Vanderbilt University Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • The Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

5 years to 17 years (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Romosozumab: 12 - < 18 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
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.
Drug: Romosozumab
Participants will receive multiple doses of romosozumab via a SC injection.
Experimental: Romosozumab: 5 - < 12 Years of Age
Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
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.
Drug: Romosozumab
Participants will receive multiple doses of romosozumab via a SC injection.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Serum Concentration (Cmax) of Romosozumab
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Day 1 to end of study (up to Day 169); median duration on study was 5.55 months

TEAEs were adverse events (AEs) that started on or after first dose of investigational product up to the end of study (up to Day 169). Any clinically significant changes in vital signs, electrocardiogram parameters, physical exam findings, and clinical laboratory parameters were reported as TEAEs.

Injection site reactions were events of interest (EOI) for this study.
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
Time Frame: Baseline (Day 1), Day 57, Day 85, and Day 169
Facial nerve (cranial nerve VII) function was assessed clinically by facial symmetry inspection at rest, followed by assessment of the symmetry of specific facial movements: raising eyebrows, closing the eyes, blowing out the cheeks, smiling, pursing and closing the lips. Results of the cranial nerve examination were classed as 0 = Normal; 1 = Abnormal not clinically significant; and 2 = Abnormal clinically significant. An increase from baseline indicates an increase in abnormal clinical findings on the cranial nerve VII examination.
Baseline (Day 1), Day 57, Day 85, and Day 169
Number of Participants With Anti-romosozumab Antibodies
Time Frame: Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169
Treatment-boosted anti-romosozumab antibody was defined as binding antibody positive at baseline with a >4 x increase in magnitude post-baseline. Transient results were defined as negative results at the participant's last time point tested within the study period.
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)
Time Frame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points.
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)
Time Frame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points.
Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine
Time Frame: DXA scans were during screening (baseline) and at Day 85 and Day 169
BMD was assessed by dual energy X-ray absorptiometry (DXA) scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
DXA scans were during screening (baseline) and at Day 85 and Day 169
Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine
Time Frame: DXA scans were during screening (baseline) and at Day 85 and Day 169
BMC was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
DXA scans were during screening (baseline) and at Day 85 and Day 169
Percentage Change From Baseline in Lumbar Spine Bone Area
Time Frame: DXA scans were during screening (baseline) and at Day 85 and Day 169
Bone area was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
DXA scans were during screening (baseline) and at Day 85 and Day 169
Mean Change From Baseline in Lumbar Spine BMD Z-Score
Time Frame: DXA scans were during screening (baseline) and at Day 85 and Day 169
Lumbar spine BMD was assessed by DXA scans. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from baseline indicated an improvement in lumbar spine BMD.
DXA scans were during screening (baseline) and at Day 85 and Day 169

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: MD, Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 21, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 11, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 18, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20160227
  • 2017-004972-74 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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 Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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