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Open-label Extension Denosumab Study in Children and Young Adults With Osteogenesis Imperfecta

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ClinicalTrials.gov Identifier: NCT03638128
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : September 30, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
To evaluate long-term safety of denosumab in subjects with pediatric osteogenesis imperfecta (OI) who completed end of study (EOS) on Study 20130173.

Condition or disease Intervention/treatment Phase
Osteogenesis Imperfecta (OI) Drug: Denosumab Other: No treatment Drug: Alternative osteoporosis medications Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Single-arm Open-label Extension Study to Assess Long-term Safety and Efficacy of Current or Prior Treatment With Denosumab in Children/Young Adults With Osteogenesis Imperfecta
Actual Study Start Date : July 26, 2018
Estimated Primary Completion Date : March 11, 2024
Estimated Study Completion Date : March 11, 2024


Arm Intervention/treatment
Experimental: Denosumab 3-Month Dosing Regimen Drug: Denosumab
clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL).

Active Comparator: Alternative Treatment
Alternative osteoporosis medication/s at the discretion of the investigator, including the commercially available denosumab on a 6-month dosing regimen.
Drug: Denosumab
clear, colorless to slightly yellow, preservative free liquid, in single-use 3.0 mL glass vials containing a deliverable dose of 120mg/1.7 mL (70 mg/mL).

Drug: Alternative osteoporosis medications
Alternative osteoporosis medication/s at the discretion of the investigator.

Active Comparator: No Intervention
Subjects who discontinue any osteoporosis medication when joining Study 20170534 for off-treatment observation.
Other: No treatment
No treatment administered for off-treatment observation.




Primary Outcome Measures :
  1. Subject incidence of treatment-emergent adverse events. [ Time Frame: 24 Months ]
  2. Subject incidence of serious treatment-emergent adverse events. [ Time Frame: 24 Months ]
  3. Subject incidence of treatment-emergent adverse events of special interest. [ Time Frame: 24 Months ]
  4. Subject incidence of antidenosumab antibodies. [ Time Frame: 24 Months ]
  5. Number of subjects with clinically significant changes from baseline in laboratory values. [ Time Frame: Baseline to 24 Months ]
  6. Number of subjects with clinically significant changes from baseline in vital signs. [ Time Frame: Baseline to 24 Months ]
  7. Subject incidence of metaphyseal index Z-score above age-appropriate normal range. [ Time Frame: 24 Months ]
  8. Subject incidence of abnormal molar eruption. [ Time Frame: 24 Months ]
  9. Subject incidence of mandibular shaping. [ Time Frame: 24 Months ]

Secondary Outcome Measures :
  1. Change from baseline in bone mineral density (BMD) of lumbar spine and proximal femur [ Time Frame: Baseline and at 12 and 24 months ]
    Changes in BMD Z score of lumbar spine (total hip and femoral neck) from Study 20170534 baseline as assessed by dual x-ray absorptiometry (DXA), at 12 and 24 months.

  2. Change from Study 20130173 baseline in bone mineral density (BMD) of lumbar spine and proximal femur [ Time Frame: Study 20130173 baseline and at 12 and 24 months ]
    Changes in BMD Z score of lumbar spine (total hip and femoral neck) from Study 20130173 baseline as assessed DXA, at 12 and 24 months.

  3. Actual values of bone mineral density (BMD) of lumbar spine and proximal femur [ Time Frame: Study 20130173 baseline, Study 20170534 baseline, and at 12 and 24 months ]
    Actual values of BMD Z score of lumbar spine and proximal femur (total hip and femoral neck) from Study 20170534 baseline. and from Study 20130173 baseline, as assessed by DXA at baseline (both studies 20130173 and 20170534) and at 12 and 24 months.

  4. Subject incidence of X-ray confirmed new and worsening vertebral fractures [ Time Frame: Baseline to 12 and 24 months ]
    Subject incidence of X-ray confirmed new and worsening vertebral fractures from Study 20170534 baseline to 12 and 24 months.

  5. Subject incidence of X-ray confirmed new vertebral fractures [ Time Frame: Baseline to 12 and 24 months ]
    Subject incidence of X-ray confirmed new vertebral fractures from Study 20170534 baseline to 12 and 24 months.

  6. Subject incidence of X-ray confirmed long bone fractures and new and worsening vertebral fractures [ Time Frame: Baseline to 12 and 24 months ]
    Subject incidence of X-ray confirmed long bone, and new and worsening vertebral fractures from Study 20170534 baseline to 12 and 24 months.

  7. Incidence of vertebral fractures [ Time Frame: Baseline and at 12 and 24 months ]
    Incidence of vertebral fractures from Study 20170534 baseline to 12 and 24 months.

  8. Incidence of nonvertebral fractures [ Time Frame: Baseline to 12 and 24 months ]
    Incidences of nonvertebral fractures from Study 20170534 baseline to 12 and 24 months.

  9. Change from baseline in growth velocity [ Time Frame: Baseline and at 12 and 24 months ]
    Change from Study 20170534 baseline in growth velocity (determined by calculating age- adjusted Z-scores for height, weight, and BMI) at 12 and 24 months.

  10. Change from Study 20130173 baseline in growth velocity [ Time Frame: Study 20130173 baseline and at 12 and 24 months ]
    Change from Study 20130173 baseline in growth velocity (determined by calculating age- adjusted Z-scores for height, weight, and BMI) at 12 and 24 months.

  11. Denosumab 3-Month regimen in 20170534: Change from baseline in bone mineral density (BMD) of lumbar spine and proximal femur [ Time Frame: Baseline to 6 and 12 months ]
    Changes in BMD Z score of lumbar spine (total hip and femoral neck) from baseline of 3-Month Dosing regimen for 20170534, as assessed by DXA, to 6 and 12 months.

  12. Denosumab 3-Month regimen in 20170534: Actual values of bone mineral density (BMD) of lumbar spine and proximal femur [ Time Frame: Baseline, and at 6 and 12 months ]
    Actual values of BMD Z score of lumbar spine and proximal femur (total hip and femoral neck) from baseline in 3-Month Dosing regimen for 20170534, as assessed by DXA, and at 6 and 12 months.

  13. Denosumab 3-Month regimen in 20170534: Change from baseline in growth velocity [ Time Frame: Baseline and at 12 Months ]
    Change from baseline of 3-Month Dosing Regimen for 20170534 in growth velocity (determined by calculating age-adjusted Z-scores for height, weight, and BMI) at 12 months.

  14. Denosumab 3-Month regimen in 20170534: Subject incidence of X-ray confirmed new and worsening vertebral fractures [ Time Frame: Baseline to 12 months ]
    Subject incidence of X-ray confirmed new and worsening vertebral fractures from baseline of 3-Month Dosing Regimen for Study 20170534 to 12 months.

  15. Denosumab 3-Month regimen in 20170534: Subject incidence of X-ray confirmed new vertebral fractures [ Time Frame: Baseline to 12 months ]
    Subject incidence of X-ray confirmed new vertebral fractures from baseline of 3-Month Dosing Regimen for Study 20170534 to 12 months.

  16. Denosumab 3-Month regimen in 20170534: Subject incidence of X-ray confirmed long bone fractures and new and worsening vertebral fractures [ Time Frame: Baseline to 12 months ]
    Subject incidence of X-ray confirmed long bone fractures and new and worsening vertebral fractures from baseline of 3-Month Dosing Regimen for 20170534 to 12 months.

  17. Denosumab 3-Month regimen in 20170534: Incidences of vertebral and nonvertebral fractures [ Time Frame: Baseline to 12 months ]
    Incidence of vertebral and nonvertebral fractures from baseline of 3-Month Dosing Regimen for 20170534 to 12 months.



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has provided informed consent/assent prior to initiation of any Study 20170534 specific activities/procedures. Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
  • Subject is currently/was enrolled in Study 20130173 and completed the 20130173 End of Study (EOS) visit (regardless of completing or ending investigational product early) OR subjects who do not reconsent/rassent to transition to 3-Month Dosing Regimen on Study 20130173 are also eligible for enrollment OR early terminated from Study 20130173 as a result of meeting BMD Z-score investigational product stopping criteria and was required to early terminate from the study.

Exclusion Criteria:

  • Treatment with any prohibited proscribed medications while receiving denosumab. Eligibility into study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For subjects off-treatment (observation only), no prohibited medications apply.- Subjects currently receiving treatment in another investigational device or drug study other than Study 20130173. Other investigational procedures while participating in this study are excluded.
  • For subjects expected to receive investigational product (denosumab) at study day 1: Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of denosumab. Females of childbearing potential (Tanner Stage greater than or equal to 2) should only be included in the study after a negative highly sensitive urine or serum pregnancy test. For study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For Subjects off-treatment (observation only), no exclusion applies.
  • For subjects expected to receive investigational product (denosumab) at study day 1: Female subjects of childbearing potential unwilling to practice true sexual abstinence (refrain from heterosexual intercourse) or use 1 highly effective method of contraception during treatment and for an additional 5 months after the last dose of investigational product (denosumab). For study treatment with alternative osteoporosis medication/s of investigator's choice, follow contraception guidelines per the specific alternative osteoporosis medication/s selected. For subjects not receiving any investigational product (observation only), no contraception required.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03638128


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03638128    
Other Study ID Numbers: 20170534
2018-000550-21 ( EudraCT Number )
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: September 30, 2021
Last Verified: September 2021
Individual Participant Data (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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
OI
Bone.
Additional relevant MeSH terms:
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Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs