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

• Status: Completed
• Trial end date: 2020-02-03
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Eastern Ontario
• Treatments: Denosumab; Diphosphonates; Zoledronic Acid

Criteria

Inclusion Criteria:

1. Subject or subject's legally acceptable representative has provided informed consent.

2. Children aged 4 to 16 years at the time of enrolment.

3. 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:

1. 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

2. 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

3. 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.

Exclusion Criteria:

1. Any child for whom the treating physician feels participation is not advised.

2. Prior treatment with an osteoporosis agent (e.g. bisphosphonate).

3. Renal insufficiency defined as an eGFR less than 60ml/min/1.73m2.

4. Active or prior diagnosis of malignancy or undergoing investigations for a suspected childhood cancer.

5. Currently breastfeeding or plans to breastfeed during the study.

6. Pregnancy (verified by pre-treatment pregnancy test in all menstruating or sexually active females).

7. Untreated vitamin D deficiency, defined as a serum 25OHD level <50nmol/L.

8. Untreated hypocalcemia, defined as a serum ionized calcium level <1.1mmol/L.

9. Active or historic eczema/cellulitis.

10. Children planning dental procedures and/or dental surgery during the course of the study.

11. Children with a documented history of atrial fibrillation.

12. Children with asthma who are acetylsalicylic acid (ASA) sensitive.

13. Children that have had parathyroid or thyroid surgery.

14. Children who are allergic to rubber or latex.

15. Males with a pregnant partner.