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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02352753
Ethics application status
Date submitted
28/01/2015
Date registered
2/02/2015
Date last updated
22/07/2021

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 - Single Arm Study


Treatment: Drugs: Denosumab
All subjects who remain on-study (have not previously completed Month 36/End of Study (EOS) under the 6-Month Dosing Regimen) will be eligible to transition to the 3-Month Dosing Regimen.Approximately 150 subjects will be enrolled. Approximately 120 subjects will transition to the 3-Month Dosing Regimen. No additional subjects will be enrolled into this study. All subjects will receive denosumab 1 mg/kg (up to a maximum of 60 mg) subcutaneously every 3 months for a minimum of 12 months, and all subjects will receive appropriate calcium and vitamin D.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in lumbar spine BMD Z-score, as assessed by DXA - Change from baseline in lumbar spine BMD Z-score, as assessed by DXA, at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Change in lumbar spine BMD Z-score, as assessed by DXA, at 6 months - Change in lumbar spine BMD Z-score, as assessed by DXA, at 6 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Change in proximal femur BMD Z-score, as assessed by DXA - Change in proximal femur BMD Z-score, as assessed by DXA, at 6 and 12 months (in subjects 5 years of age and older) in subjects receiving the 3-Month Dosing Regimen
Timepoint [2] 0 0
6 and 12 months
Secondary outcome [3] 0 0
Incidence of X-ray confirming long bone and new and worsening vertebral fractures - Incidence of X-ray confirmed long bone and new and worsening vertebral fractures from last 12 months on 6-Month Dosing Regimen to 12 months on 3-Month Dosing Regimen
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Incidence of X-ray confirmed new and worsening vertebral fractures - Incidence of X-ray confirmed new and worsening vertebral fractures from last 12 months on 6-Month Dosing Regimen to 12 months on 3-Month Dosing Regimen
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Incidence of X-ray confirming new vertebral fractures - Incidence of X-ray confirmed new vertebral fractures from last 12 months on 6-Month Dosing Regimen to 12 months on 3-Month Dosing Regimen
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Incidence of improving vertebral fractures - Subject incidence of improving vertebral fractures from last 12 months on 6-Month Dosing Regimen to 12 months on 3-Month Dosing Regimen
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Incidence of vertebral and nonvertebral fractures - Incidence of vertebral and nonvertebral fractures from last 12 months on 6-Month Dosing Regimen to 12 months on 3-Month Dosing Regimen (in subjects 5 years of age or older)
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
Change in Child Health Questionnaire (CHQ)-Parent Form (PF)-50 Physical Summary - Change from baseline in CHQ-PF-50 Physical Summary score at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Change in CHQ-PF-50 Psychological Summary score - Change from baseline in CHQ-PF-50 Psychological Summary score at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Childhood Health Assessment Questionnaire (CHAQ) Disability Index score - Change from baseline in CHAQ Disability Index score at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [10] 0 0
12 Months
Secondary outcome [11] 0 0
Change in Wong-Baker Faces Pain Rating Scale (WBFPRS) - Change in Wong-Baker Faces Pain Rating Scale (WBFPRS) at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Serum concentration of denosumab - Serum concentration of denosumab and serum bone turnover markers (BTM) on days 1, 10, 30, 60, and every 3 months in subjects on 3-Month Dosing Regimen
Timepoint [12] 0 0
Days 1, 10, 30, and 60 and every 3 months
Secondary outcome [13] 0 0
Change in growth velocity at 12 months - Change from baseline in growth velocity (determined by calculating age-adjusted Z-scores for height, weight and body mass index [BMI]) at 12 months in subjects receiving the 3-Month Dosing Regimen
Timepoint [13] 0 0
12 months
Secondary outcome [14] 0 0
Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, and 9 months - Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, and 9 months (pharmacokinetic [PK]/BTM substudy; 6-Month Dosing Regimen)
Timepoint [14] 0 0
1, 10, and 30 days, and 3, 6, and 9 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
Gender
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
N/A
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
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
This is a prospective, multicenter, single-arm study in children 2 to 17 years of age with OI
to evaluate efficacy and safety of denosumab.
Trial website
https://clinicaltrials.gov/show/NCT02352753
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

Summary results
Other publications