Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders

NCT02418273 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 1504269855
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate denosumab as a novel treatment for bone loss in children treated with glucocorticoids for rheumatic disorders. This is a pilot Phase 1/2, randomized open-label, 12-month clinical trial of denosumab to assess its effect on bone resorption markers and bone mineral density (BMD) in children with rheumatic disorders, age 4 to 16 years, recruited within 1 month of starting a chronic systemic glucocorticoid regimen. Primary outcomes include suppression of bone turnover markers and safety assessments. Secondary outcomes include changes in bone density as measured by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) densitometry at the radius and tibia.

Conditions

Osteoporosis; Juvenile Rheumatoid Arthritis; Dermatomyositis; Polyarthritis; Systemic Lupus Erythematosis; Vasculitis; Glucocorticoid-induced Osteoporosis

Keywords

denosumab; pediatric; rheumatology; osteoporosis; glucocorticoid

Outcome Measures

Primary Outcomes (1)

• Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio).

  2 weeks, 1 month, 2 month, 3 month after each dose day.

Secondary Outcomes (16)

• The duration of suppression of the NTX/creatinine ratio

  up to six months after each dose day

• The changes in bone specific alkaline phosphorus

  From baseline to 1 week, 1,3,6 months after each dose day

• Changes of BMD spine Z-scores

  12 month

• Changes of BMD Total body less head (TBLH) Z-scores

  12 month

• Changes of volumetric BMD on peripheral quantitative computed tomography

  12 month

Study Arms (2)

Denosumab

EXPERIMENTAL

These subjects will receive two sequential doses of denosumab

Drug: denosumab

No drug intervention

NO INTERVENTION

These subjects do not receive denosumab

Interventions

denosumab DRUG

These subjects will receive two doses of denosumab.

Also known as: Prolia

Denosumab

Eligibility Criteria

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

You may qualify if:

• Age 4 to 16 years of age.
• Diagnosis of one of the following by a rheumatologist using standard criteria: juvenile dermatomyositis, juvenile idiopathic arthritis, systemic arthritis, seronegative or seropositive polyarthritis, psoriatic arthritis, systemic lupus or systemic vasculitis.
• Within 1 month of initiating glucocorticoids ≥0.5 mg/kg prednisone equivalent daily, planned for ≥ 6 months.
• BMD by DXA with Z-score \< 0.0 on screening at lumbar spine or total body less head (TBLH).

You may not qualify if:

• Previous treatment with a bisphosphonate, or other osteoporosis medication.
• Metabolic bone disorders besides glucocorticoid-induced osteoporosis; other disorders treated with systemic glucocorticoids (inflammatory bowel disease, severe pulmonary disease, nephrotic syndrome, etc.).
• Intent to treat with a tumor necrosis factor inhibitor or Interleukin 6 receptor antagonist during the first 6 months.
• Glomerular filtration rate \< 30ml/min \[pediatric estimated glomerular filtration rate = 0.413\*(height/serum creatinine)\] 75
• Planned orthopedic or other major surgery during the course of the study (at the time of enrollment)
• Significant dental caries, or plans to undergo invasive oral procedures during the subsequent 12 months.
• Known allergy to latex (drug packaging includes a natural rubber stopper), fructose intolerance or other denosumab contraindication.
• hydroxyvitamin D (25OHD) level \< 32 ng/dl. Subjects with 25OHD \<32 ng/ml may be given cholecalciferol and rescreened.
• Hypocalcemia at screening (total serum calcium \< 8.5 mg/dl after correction for albumin level).
• Chronic ventilator dependence, or other conditions increasing risk of participation.
• Pregnancy, or refusal to use acceptable contraception or abstain during the protocol (post-pubertal female).

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Osteoporosis; Arthritis, Juvenile; Dermatomyositis; Arthritis; Vasculitis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Polymyositis; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Skin Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Erik Imel, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Pediatrics

Study Record Dates

• First Submitted: April 6, 2015
• First Posted: April 16, 2015
• Study Start: August 1, 2019
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: December 6, 2019

Record last verified: 2019-12

Locations

US (1)