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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05972551




Registration number
NCT05972551
Ethics application status
Date submitted
24/07/2023
Date registered
2/08/2023
Date last updated
13/06/2024

Titles & IDs
Public title
Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
Scientific title
A Phase 3, Open-Label, Multicenter, Randomized Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
Secondary ID [1] 0 0
2023-503294-37
Secondary ID [2] 0 0
20200105
Universal Trial Number (UTN)
Trial acronym
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 - Romosozumab
Treatment: Drugs - Bisphosphonate

Experimental: Romosozumab - Participants will receive romosozumab once a month (QM) for 12 months.

Active comparator: Standard of Care Bisphosphonate - Participants will receive bisphosphonates per local standard of care treatment regimens, as determined by the investigator for 12 months.


Treatment: Drugs: Romosozumab
Subcutaneous (SC) injection

Treatment: Drugs: Bisphosphonate
Administration determined by investigator according to the local standard of care
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Clinical Fractures
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Number of Any Fractures
Timepoint [2] 0 0
12 months
Primary outcome [3] 0 0
Change from Baseline to 6 Months in Lumbar Spine BMD Z-score
Timepoint [3] 0 0
Baseline and 6 months
Secondary outcome [1] 0 0
Change from Baseline to 12 Months in Lumbar Spine BMD Z-score
Timepoint [1] 0 0
Baseline and 12 months
Secondary outcome [2] 0 0
Change from Baseline to 6 Months in Total Hip BMD Z-score
Timepoint [2] 0 0
Baseline and 6 months
Secondary outcome [3] 0 0
Change from Baseline to 12 Months in Total Hip BMD Z-score
Timepoint [3] 0 0
Baseline and 12 months
Secondary outcome [4] 0 0
Change from Baseline to 6 Months in Femoral Neck BMD Z-score
Timepoint [4] 0 0
Baseline and 6 months
Secondary outcome [5] 0 0
Change from Baseline to 12 Months in Femoral Neck BMD Z-score
Timepoint [5] 0 0
Baseline and 12 months
Secondary outcome [6] 0 0
Number of Participants with Any Fractures
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Number of Participants with Clinical Fractures
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Number of Participants with New or Worsening Vertebral Fractures
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Number of Participants with Nonvertebral Fractures
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Number of New or Worsening Vertebral Fractures
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Number of Nonvertebral Fractures
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Number of Long Bone Fractures
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
Change from Baseline in Child Health Questionnaire - Parent Version (CHQ-PF-50) Physical Summary Score
Timepoint [13] 0 0
Baseline and 12 months
Secondary outcome [14] 0 0
Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ-CV) Disability Score
Timepoint [14] 0 0
Baseline and 12 months
Secondary outcome [15] 0 0
Change from Baseline in the Wong-Baker Faces Pain Rating Scale
Timepoint [15] 0 0
Baseline and 12 months
Secondary outcome [16] 0 0
Serum Concentration of Romosozumab
Timepoint [16] 0 0
Day 1 to Month 12
Secondary outcome [17] 0 0
Number of Participants who Experience Treatment-emergent Adverse Events (TEAEs) at 12 Months
Timepoint [17] 0 0
12 months
Secondary outcome [18] 0 0
Number of Participants with Anti-romosozumab Antibodies at 12 Months
Timepoint [18] 0 0
12 months
Secondary outcome [19] 0 0
Number of Participants who Experience TEAEs from Month 12 to Month 15
Timepoint [19] 0 0
Month 12 to Month 15
Secondary outcome [20] 0 0
Number of Participants with Anti-romosozumab Antibodies from Month 12 to Month 15
Timepoint [20] 0 0
Month 12 to Month 15
Secondary outcome [21] 0 0
Number of Participants who Experience TEAEs at 15 Months
Timepoint [21] 0 0
15 months
Secondary outcome [22] 0 0
Number of Participants with Anti-romosozumab Antibodies at 15 Months
Timepoint [22] 0 0
15 months
Secondary outcome [23] 0 0
Number of Participants with a Narrowing from Baseline to 6 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
Timepoint [23] 0 0
Baseline and 6 months
Secondary outcome [24] 0 0
Number of Participants with a Narrowing from Baseline to 12 Months in the Intracranial Nerve Tract in the Cranium and Vault of the Skull
Timepoint [24] 0 0
Baseline and 12 months

Eligibility
Key inclusion criteria
* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.

OR

* Participant's legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the participant has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
* Ambulatory male and female children and adolescents, age 5 to <18 years, including ambulatory with assistance as defined in the pediatric osteogenesis imperfecta (OI) population.
* Clinical diagnosis of OI, defined as clinical history consistent with type I, III, or IV OI as determined by presence of expected phenotype (examples include: facial shape, voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture pattern) and lack of additional features unrelated to type I, III, or IV OI (eg, blindness, mental retardation, neuropathy, and craniosynostosis).

o If familial, also must be autosomal dominant.
* Meets at least one of the following:

* 3 or more fractures within the previous 2 years, or
* 1 or more nonvertebral fracture(s) within the previous 2 years and at least 1 prevalent vertebral fracture, or
* 2 or more prevalent vertebral fractures.
* Lumbar spine Z-score of =-1.0.
Minimum age
5 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Disease Related

* History of an electrophoresis pattern inconsistent with type I, III or IV OI.
* History of known mutation in a gene other than collagen type I alpha 1/collagen type I alpha 2 (COL1A1/COL1A2) causing OI or other metabolic bone disease.
* History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation.

Other Medical Conditions

* History of osteomalacia or rickets.
* Body weight less than 14 kg or greater than 90 kg.
* History of other bone diseases that affect bone metabolism (e.g., but not limited to 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.
* Evidence of untreated or unhealed oral infections.
* Unhealed or planned invasive dental or tooth procedure as determined by treating dentist; removal of baby teeth is acceptable and not considered an invasive dental procedure.
* Unhealed fracture as defined by orthopedic opinion.
* Osteotomy, rodding surgery or spinal fusion surgery within 5-months prior to screening, or not yet healed per orthopedic surgeon.
* History of clinically significant valvular heart disease previously documented with local echocardiogram results.
* Evidence of any of the following:

* Current hyper- or hypoparathyroidism (parathyroid hormone outside the normal range).
* Renal disease: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2 (calculated by the bedside Schwartz equation at screening) eGFR (mL/min/1.73 m^2) = 0.413 X (height/serum creatinine)

1. (Height is in centimeters, and serum creatinine is in mg/dL).
* Current hypocalcemia (albumin-adjusted serum calcium <lower limit of normal [LLN]) or hypercalcemia (albumin-adjusted serum calcium > upper limit of normal [ULN] of the laboratory's reference range).
* Serum vitamin D <20 ng/mL; rescreening for Vitamin D level < 20 ng/mL will be allowed, after adequate supplementation.
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 x ULN.
* Total bilirubin (TBL) >1.5 x ULN (participants with Gilbert syndrome are eligible).
* Serum phosphorus < LLN for age.
* Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation (e.g., headache induced by coughing or straining for stool, visual disturbances, paresthesias or weakness).
* History of malabsorption (in children with serum albumin <LLN, malabsorption should be clinically ruled out by the investigator to confirm eligibility).
* History of long QT syndrome.
* History of malignancy.
* History of any solid organ or bone marrow transplant.
* History of hyper- or hypothyroidism, unless participant is on stable therapy > 6-months and has supporting laboratory documentation within 6-months prior to or at screening indicating normal serum thyroid-stimulating hormone (TSH) value.
* Known intolerance to calcium or vitamin D supplements.
* History of osteonecrosis of the jaw (ONJ).

Prior/Concomitant Therapy

* Prior treatment with:
* Romosozumab or other anti-sclerostin antibody within 12-months prior to screening.
* Fluoride or strontium for bone disease.
* Parathyroid hormone (PTH) or PTH derivatives within 12-months prior to screening.
* Denosumab within 12-months after the last injection prior to first dose of romosozumab.
* Administration of any of the following treatments within 3-months prior to screening:
* Systemic glucocorticoids (= 5.0 mg prednisone equivalent/day for more than 10 days) within 3-months prior to screening. Topical and inhaled glucocorticoids will be allowed.
* Growth hormone (participants on stable dose of growth hormone for at least 3-months prior to screening will be allowed).
* Calcitonin.
* Other bone active drugs including anticonvulsants (except gabapentin and benzodiazepines) and heparin (unless low molecular weight heparin).
* Chronic systemic ketoconazole, androgens (except participants who have received testosterone therapy for physiologic replacement in the setting of documented hormonal deficiency), adrenocorticotropic hormone (ACTH), cinacalcet, aluminum, lithium, protease inhibitors, gonadotropin-releasing hormone agonists.
* Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol, sotalol, amiodarone, erythromycin, or clarithromycin). Refer to CredibleMeds.org for the complete list of medications which can impact QT interval.

Prior/Concurrent Clinical Study Experience

- Currently receiving treatment in another investigational device or drug study, or less than 2 years since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Other Exclusions

* Positive blood screen for hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HepCAb).
* Participants with symptomatic human immunodeficiency virus (HIV) with bone involvement or those that have been in a serious clinical condition.
* Less than 2 evaluable vertebrae by dual-energy x-ray absorptiometry evaluation in the region of interest, L1-L4, as confirmed by the central imaging laboratory.
* Any planned major surgery, including skeletal surgery (eg, rodding surgery, spinal surgery) within the next 12-months from Day 1 that would interfere with study procedures or would require missing of any investigational product
* Female participants of childbearing potential unwilling to use a highly effective method of contraception during treatment and for an additional 3-months after the last dose of investigational product or non-investigational product.
* Female participants who are breastfeeding or who plan to breastfeed while on study through 3-months after the last dose of investigational product or non-investigational product.
* Female participants planning to become pregnant or donate eggs while on study through 3-months after the last dose of investigational product or non-investigational product.
* Female participants of childbearing potential with a positive pregnancy test assessed at Screening and/or Day 1 by a highly sensitive urine or serum pregnancy test.
* Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 3-months after the last dose of investigational product or non-investigational product.
* Male participants unwilling to abstain from donating sperm during treatment and for an additional 3-months after the last dose of investigational product or non-investigational product.
* Participant has known sensitivity to any of the products to be administered during dosing.
* Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the participant and investigator's knowledge.
* 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 participant safety or interfere with the study evaluation, procedures or completion

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
27/05/2027
Actual
Sample size
Target
106
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Monash Childrens Hospital - Clayton
Recruitment hospital [2] 0 0
Perth Childrens Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6909 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Indiana
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Austria
State/province [5] 0 0
Linz
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
France
State/province [9] 0 0
Paris Cedex 15
Country [10] 0 0
Germany
State/province [10] 0 0
Koeln
Country [11] 0 0
Hungary
State/province [11] 0 0
Budapest
Country [12] 0 0
Japan
State/province [12] 0 0
Okayama
Country [13] 0 0
Japan
State/province [13] 0 0
Osaka
Country [14] 0 0
Poland
State/province [14] 0 0
Lodz
Country [15] 0 0
Poland
State/province [15] 0 0
Tychy
Country [16] 0 0
Slovakia
State/province [16] 0 0
Bratislava
Country [17] 0 0
Spain
State/province [17] 0 0
Cataluña
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Spain
State/province [19] 0 0
País Vasco
Country [20] 0 0
Switzerland
State/province [20] 0 0
Basel
Country [21] 0 0
Switzerland
State/province [21] 0 0
Lausanne
Country [22] 0 0
Turkey
State/province [22] 0 0
Ankara
Country [23] 0 0
Turkey
State/province [23] 0 0
Istanbul
Country [24] 0 0
Turkey
State/province [24] 0 0
Izmir
Country [25] 0 0
Turkey
State/province [25] 0 0
Trabzon
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Glasgow

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the effect of romosozumab treatment for 12-months compared with bisphosphonate(s) on the number of clinical fractures at 12-months; the number of any fractures at 12-months and change in lumbar spine bone mineral density (BMD) Z-score at 6-months.
Trial website
https://clinicaltrials.gov/study/NCT05972551
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
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05972551