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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02352753




Registration number
NCT02352753
Ethics application status
Date submitted
28/01/2015
Date registered
2/02/2015

Titles & IDs
Public title
Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
Scientific title
To Evaluate the Effect of Denosumab in Lumbar Spine Bone Mineral Density (BMD) Z-score at 12 Months, as Assessed by Dual-energy X-ray Absorptiometry (DXA), in Children 2 to 17 Years of Age (at the Time of Screening) on a 3-Month Dosing Regimen With OI
Secondary ID [1] 0 0
2014-000184-40
Secondary ID [2] 0 0
20130173
Universal Trial Number (UTN)
Trial acronym
OI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteogenesis Imperfecta 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Denosumab

Experimental: Denosumab - Participants received denosumab 1 mg/kg (up to a maximum of 60 mg) subcutaneously every 6 months (Q6M) for up to 36 months.

Early efficacy and PK data from Q6M dosing supported adjustment of the dosing regimen from Q6M to every 3 months (Q3M). Participants enrolled and still receiving denosumab were transitioned from Q6M to Q3M dosing schedule. Participants could transition to Q3M dosing schedule up to and including the date they attended for their month 36 visit under the Q6M dosing regimen. Those participants received denosumab during the Q3M dosing regimen for 12 months. Participants who transition to Q3M at month 18 of the Q6M dosing regimen received denosumab Q3M for up to 18 months.


Treatment: Drugs: Denosumab
Subcutaneous (SC) injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score at 12 Months
Timepoint [1] 0 0
Baseline and 12 months
Secondary outcome [1] 0 0
Change From Baseline in Lumbar Spine BMD Z-score at 6 Months
Timepoint [1] 0 0
Baseline and 6 months
Secondary outcome [2] 0 0
Change From Baseline in Proximal Femur BMD Z-score at 6 and 12 Months
Timepoint [2] 0 0
Baseline, 6 and 12 months
Secondary outcome [3] 0 0
Percentage of Participants With at Least 1 X-ray Confirmed Long Bone or New and Worsening Vertebral Fracture
Timepoint [3] 0 0
Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Secondary outcome [4] 0 0
Percentage of Participants With at Least 1 X-ray Confirmed New and Worsening Vertebral Fracture
Timepoint [4] 0 0
Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Secondary outcome [5] 0 0
Percentage of Participants With at Least 1 X-ray Confirmed New Vertebral Fracture
Timepoint [5] 0 0
Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Secondary outcome [6] 0 0
Percentage of Participants Wth at Least 1 X-ray Confirmed Improving Vertebral Fracture
Timepoint [6] 0 0
Q3M Dosing Regimen: Baseline up to 12 months
Secondary outcome [7] 0 0
Percentage of Participants With at Least 1 Vertebral and Nonvertebral Fracture
Timepoint [7] 0 0
Q6M Dosing Regimen: Last 12 months of treatment (median treatment duration was 730.0 days); Q3M Dosing Regimen: Day 1 up to 12 months
Secondary outcome [8] 0 0
Change From Baseline in Child Health Questionnaire-Parent Form Physical Summary Score (CHQ-PF-50) at 12 Months
Timepoint [8] 0 0
Baseline and 12 months
Secondary outcome [9] 0 0
Change From Baseline in CHQ-PF-50 Psychological Summary Score at 12 Months
Timepoint [9] 0 0
Baseline and 12 months
Secondary outcome [10] 0 0
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index Score at 12 Months
Timepoint [10] 0 0
Baseline and 12 months
Secondary outcome [11] 0 0
Change From Baseline in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 Months
Timepoint [11] 0 0
Baseline and 12 months
Secondary outcome [12] 0 0
Serum Concentration of Denosumab
Timepoint [12] 0 0
Days 1 (predose), 10, 30, and 60, & weeks 12, 24, 36, 48, 60, 72 (end of study visit), early termination visit, & follow-up visit 12 weeks after last dose (average duration of treatment: 231 days)
Secondary outcome [13] 0 0
Serum Bone Turnover Marker (BTM) - Serum Type I Collagen C Telopeptide
Timepoint [13] 0 0
Baseline and Days 10 and 30, and Months 3, 6, 9, 12, 15 and 18
Secondary outcome [14] 0 0
BTM - Bone-specific Alkaline Phosphatase (BSAP)
Timepoint [14] 0 0
Baseline and Days 10 and 30, and Months 3, 6, 9, 12, and 15
Secondary outcome [15] 0 0
Change From Baseline in Growth Velocity at 12 Months
Timepoint [15] 0 0
Baseline and 12 months

Eligibility
Key inclusion criteria
• Eligibility criteria relates to initial enrollment into this study (6-Month Dosing Regimen). Subjects reconsenting to a 3-Month Dosing Regimen will not repeat eligibility assessments



• Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI Clinical severity of OI as defined by 2 or more prevalent vertebral compression fractures; OR1 prevalent vertebral compression fracture and 1 or more nonvertebral fractures within the previous 2 years; OR 3 or more fractures within the previous 2 years.
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability or unwillingness to comply with the requirements for frequent calcium and phosphorus monitoring for 14 days after the first dose of denosumab (only applies to the first 5 subjects age 11 to17 enrolled in the study and the first 5 subjects of any age meeting the criteria for increased bone turnover
* Currently unhealed fracture or osteotomy as defined by orthopedic opinion
* Osteotomy within 5 months of screening
* Evidence of untreated oral cavities or oral infections
* Recent or planned invasive dental procedure
* Surgical tooth extraction which has not healed by screening
* History of an electrophoresis pattern inconsistent with type I to IV OI
* History of genetic testing results inconsistent with type I to IV OI
* Abnormalities of the following per central laboratory reference ranges at screening: Serum albumin corrected calcium < lower limit of normal (LLN) Serum vitamin D < 20 ng/mL; re-screening for Vitamin D level < 20 ng/mL will be allowed, after adequate supplementation
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN)
* Total bilirubin (TBL) > 1.5 x ULN (subjects with Gilbert syndrome are eligible)
* Serum phosphorus < LLN
* Serum alkaline phosphatase > 20% above the ULN or > 20% below the LLN
* Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (calculated bythe Schwartz equation at screening) Evidence of any of the following: Current hyperthyroidism (unless well-controlled on stable antithyroid therapy)
* Current clinical hypothyroidism (unless well-controlled on stable thyroid replacement therapy)
* History of hyperparathyroidism
* Current hypoparathyroidism
* Current, uncontrolled hypercalcemia (albumin-corrected serum Ca >10% ULN)
* History of osteomalacia or rickets (chart review)
* Other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia)
* History of autoimmune disease
* History of rare hereditary problems of fructose intolerance
* Positive blood screen for human immunodeficiency virus -1 or -2 antibody
* Positive blood screen for hepatitis B surface antigen or hepatitis C antibody
* Received other osteoporosis treatment or bone active treatment with the following guidelines:
* Prior treatment with

* denosumab
* fluoride or strontium for bone disease (fluoride taken for routine dental care is permitted)
* parathyroid hormone (PTH) or PTH derivatives within 12 months prior to screening
* zoledronic acid within 6 months prior to screening
* oral bisphosphonates or intravenous bisphosphonates other than zoledronic acid if the first dose of denosumab would be before their next scheduled bisphosphonate dose would have been given
* Administration of systemic glucocorticoids (= 5.0 mg prednisone equivalents/day for more than 10 days) within 3 months of screening.
* Topical and inhaled glucocorticoids will be allowed
* Administration of any of the following treatment within 3 months of screening:

* Growth hormone (subjects on stable dose of growth hormone for at least 3 months prior to screening will be allowed)
* Currently receiving treatment in another investigational drug study, or less than 30 days since ending treatment on another investigational drugstudy(s), or current or planned participation in a clinical trial that would preclude compliance with study requirements Other inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/03/2022
Sample size
Target
Accrual to date
Final
153
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Research Site - Westmead
Recruitment hospital [2] 0 0
Research Site - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Varna
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Czechia
State/province [20] 0 0
Hradec Kralove
Country [21] 0 0
Czechia
State/province [21] 0 0
Pardubice
Country [22] 0 0
Czechia
State/province [22] 0 0
Plzen
Country [23] 0 0
Czechia
State/province [23] 0 0
Praha 4
Country [24] 0 0
Czechia
State/province [24] 0 0
Zlin
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux Cedex
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 15
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
France
State/province [28] 0 0
Saint Priest en Jarez
Country [29] 0 0
France
State/province [29] 0 0
Toulouse Cedex 9
Country [30] 0 0
Germany
State/province [30] 0 0
Köln
Country [31] 0 0
Hungary
State/province [31] 0 0
Budapest
Country [32] 0 0
Italy
State/province [32] 0 0
Roma
Country [33] 0 0
Italy
State/province [33] 0 0
Verona
Country [34] 0 0
Poland
State/province [34] 0 0
Bialystok
Country [35] 0 0
Poland
State/province [35] 0 0
Lodz
Country [36] 0 0
Poland
State/province [36] 0 0
Rzeszow
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Spain
State/province [38] 0 0
Cataluña
Country [39] 0 0
Spain
State/province [39] 0 0
Comunidad Valenciana
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Birmingham
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Bristol
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Glasgow
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02352753