Denosumab for the Treatment of Osteoporosis in Children: A Pilot Study

NCT02632916 | Completed Phase 2 DMC

• 1 other identifier: DZA9DEC2015
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to acquire preliminary, pilot data over a 2-year period on the safety and efficacy of subcutaneous denosumab versus the current CHEO standard-of-care (intravenous zoledronic acid) for the treatment of osteoporosis in children. Both denosumab (1.0mg/kg) and zoledronic acid (0.025mg/kg) will be given as four doses separated by a six month interval (i.e. at baseline, 6 months, 12 months and 18 months), with follow-up to 2 years.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• The changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid.

  To observe the changes in serum ionized calcium levels at 48 hours following the administration of denosumab versus zoledronic acid. Hypocalcemia at 48 hours has been chosen as the primary outcome since this is a clinically important side effect of both denosumab and zoledronic acid, and 48 hours is around the time of the anticipated calcium nadir

  48 hours after each drug administration (48 hours post baseline and 48 hours post 6, 12 and 18 month visits)

Study Arms (2)

Zoledronic Acid

ACTIVE COMPARATOR

Intravenous zoledronic acid 0.025mg/kg

Drug: Zoledronic Acid

Denosumab

EXPERIMENTAL

Subcutaneous denosumab 1.0mg/kg

Drug: Denosumab

Interventions

Zoledronic Acid DRUG

Intravenous zoledronic acid 0.025mg/kg at baseline, 6 months, 12 months and 18 months

Zoledronic Acid

Denosumab DRUG

Subcutaneous denosumab 1.0mg/kg at baseline, 6 months, 12 months and 18 months

Denosumab

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject or subject's legally acceptable representative has provided informed consent.
• Children aged 4 to 16 years at the time of enrolment.
• Children with a history of clinically significant bone fragility in the preceding 24 months, requiring the child to have ONE or more of the following clinical profiles:
• At least one low-trauma vertebral or long bone fracture in a child with an underlying disease known to be associated with osteoporotic fractures (e.g. glucocorticoid-treated diseases, Crohn's disease, rheumatic disorders, Duchenne muscular dystrophy, other muscular dystrophies, spinal muscular atrophy, cerebral palsy); OR
• At least one low-trauma vertebral or long bone fracture in the last 24 months, in a child with a known genetic osteoporotic condition such as osteogenesis imperfecta (confirmed on molecular genetic testing); OR
• At least one low-trauma vertebral or long bone fracture in the last 24 months, in an otherwise healthy child with a diagnosis of osteoporosis confirmed on trans-iliac bone biopsy. Trans-iliac bone biopsy is a requirement in this sub-group as per the usual standard of care, as this is the only test that will definitively confirm osteoporosis in an otherwise healthy child who does not have a genetic bone fragility condition.

You may not qualify if:

• Any child for whom the treating physician feels participation is not advised.
• Prior treatment with an osteoporosis agent (e.g. bisphosphonate).
• Renal insufficiency defined as an eGFR less than 60ml/min/1.73m2.
• Active or prior diagnosis of malignancy or undergoing investigations for a suspected childhood cancer.
• Currently breastfeeding or plans to breastfeed during the study.
• Pregnancy (verified by pre-treatment pregnancy test in all menstruating or sexually active females).
• Untreated vitamin D deficiency, defined as a serum 25OHD level \<50nmol/L.
• Untreated hypocalcemia, defined as a serum ionized calcium level \<1.1mmol/L.
• Active or historic eczema/cellulitis.
• Children planning dental procedures and/or dental surgery during the course of the study.
• Children with a documented history of atrial fibrillation.
• Children with asthma who are acetylsalicylic acid (ASA) sensitive.
• Children that have had parathyroid or thyroid surgery.
• Children who are allergic to rubber or latex.
• Males with a pregnant partner.

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead

Study Sites (1)

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

Zoledronic Acid; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Leanne Ward, MD

  Children's Hospital of Eastern Ontario

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 17, 2015
• Study Start: August 1, 2016
• Primary Completion: February 3, 2020
• Study Completion: February 3, 2020
• Last Updated: June 23, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: No time frame
• Access Criteria: Access has not been made available

Locations

CA (1)