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

• ClinicalTrials.gov Identifier: NCT03638128
• Recruitment Status: Recruiting
• First Posted: August 20, 2018
• Last Update Posted: December 16, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 21, 2018
• First Posted Date: August 20, 2018
• Last Update Posted Date: December 16, 2020
• Actual Study Start Date: July 26, 2018
• Estimated Primary Completion Date: November 12, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2020)

• Subject incidence of treatment-emergent adverse events. [ Time Frame: 24 Months ]
• Subject incidence of serious treatment-emergent adverse events. [ Time Frame: 24 Months ]
• Subject incidence of treatment-emergent adverse events of special interest. [ Time Frame: 24 Months ]
• Subject incidence of antidenosumab antibodies. [ Time Frame: 24 Months ]
• Number of subjects with clinically significant changes from baseline in laboratory values. [ Time Frame: Baseline to 24 Months ]
• Number of subjects with clinically significant changes from baseline in vital signs. [ Time Frame: Baseline to 24 Months ]
• Subject incidence of metaphyseal index Z-score above age-appropriate normal range. [ Time Frame: 24 Months ]
• Subject incidence of abnormal molar eruption. [ Time Frame: 24 Months ]
• Subject incidence of mandibular shaping. [ Time Frame: 24 Months ]

• Original Primary Outcome Measures (submitted: August 16, 2018): Subject incidence of treatment-emergent adverse events. [ Time Frame: 24 Months ]

Current Secondary Outcome Measures (submitted: July 23, 2020)

• Changes in bone mineral density (BMD) of lumbar spine. [ Time Frame: At 6, 12 and 24 months ]
  Actual values and changes in BMD Z score of lumbar spine (total hip) from baseline and from Study 20130173 baseline of 3 month dosing regimen, as assessed by dual x-ray absorptiometry (DXA), to 6, 12 and 24 months.
• Changes in bone mineral density (BMD) of proximal femur (femoral neck). [ Time Frame: At 6, 12 and 24 Months ]
  Actual values and changes in BMD Z score of proximal femur (femoral neck) from baseline and from Study 20130173 baseline of 3 month dosing regimen, as assessed by dual x-ray absorptiometry (DXA), to 6, 12 and 24 months
• Incidence of X-ray confirmed long bone fractures. [ Time Frame: At 12 and 24 Months ]
  Incidence of x-ray confirmed long bone fractures from baseline and from Study 20130173 baseline of 3-month dosing regimen, to 12 and 24 months
• Incidence of X-ray confirmed new vertebral fractures. [ Time Frame: At 12 and 24 Months ]
  Incidence of x-ray confirmed new and worsening vetebral fractures from baseline and from Study 20130173 baseline of 3-month dosing regimen, to 12 and 24 months
• Incidence of X-ray confirmed worsening vertebral fractures. [ Time Frame: At 12 and 24 Months ]
  Subject incidence of X-ray confirmed long bone and worsening vertebral fractures from baseline and from Study 20130173 baseline to 12 and 24
• Incidence of vertebral fractures. [ Time Frame: At 12 and 24 Months ]
  Incidence of vertebral fractures from baseline and from Study 20130173 baseline of 3-month dosing to 12 and 24 months
• Incidence of nonvertebral fractures. [ Time Frame: At 12 and 24 Months ]
  Subject incidence of nonvertebral fractures from baseline and from Study 20130173 baseline to 12 and 24 months
• Change in growth velocity. [ Time Frame: At 12 and 24 Months ]
  Change from baseline and from Study 20130173 baseline of 3-month dosing regimen in growth velocity (determined by calculating age- adjusted Z-scores for height, weight, and BMI) at 12 and 24 months
• Changes in bone mineral density (BMD) of total hip. [ Time Frame: At 12 and 24 Months ]
  Actual values and changes in BMD Z score of total hip from baseline and from Study 20130173 baseline of 3 month dosing regimen, as assessed by dual x-ray absorptiometry (DXA), to 6, 12 and 24 months

Original Secondary Outcome Measures (submitted: August 16, 2018)

• Changes in bone mineral density (BMD) of lumbar spine. [ Time Frame: At 12 and 24 months ]
  Changes in bone mineral density (BMD) of lumbar spine assessed by dual X-ray absorptiometry (DXA).
• Changes in bone mineral density (BMD) of proximal femur (femoral neck). [ Time Frame: At 12 and 24 Months ]
  Changes in bone mineral density (BMD) of proximal femur (femoral neck) assessed by dual X-ray absorptiometry (DXA).
• Incidence of X-ray confirmed long bone fractures. [ Time Frame: At 12 and 24 Months ]
• Incidence of X-ray confirmed new vertebral fractures. [ Time Frame: At 12 and 24 Monts ]
• Incidence of X-ray confirmed worsening vertebral fractures. [ Time Frame: At 12 and 24 Months ]
• Incidence of vertebral fractures. [ Time Frame: At 12 and 24 Months ]
• Incidence of nonvertebral fractures. [ Time Frame: At 12 and 24 Months ]
• Change in growth velocity. [ Time Frame: At 12 and 24 Months ]
• Changes in bone mineral density (BMD) of total hip. [ Time Frame: At 12 and 24 Months ]
  Changes in bone mineral density (BMD) of total hip assessed by dual X-ray absorptiometry (DXA).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Open-label Extension Denosumab Study in Children and Young Adults With Osteogenesis Imperfecta
• 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
• Brief Summary: To evaluate long-term safety of denosumab in subjects with pediatric osteogenesis imperfecta(OI) completing Study 20130173.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Osteogenesis Imperfecta (OI)

Intervention

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).

Study Arms

Experimental: Denosumab

70 mg/mL solution containing 1.7 mL administered subcutaneously with a frequency of: day 1, at week 12, week 24, week 36, week 48, week 60, week 72, and week 84

Intervention: Drug: Denosumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 16, 2018): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 12, 2023
• Estimated Primary Completion Date: November 12, 2023 (Final data collection date for primary outcome measure)

Eligibility 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 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 IP 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Belgium, Canada, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03638128
• Other Study ID Numbers: 20170534; 2018-000550-21 ( 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

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 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

• Responsible Party: Amgen
• Study Sponsor: Amgen
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: December 2020