Clinical trial NCT02418273: Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders
Official title: Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Osteoporosis
Juvenile Rheumatoid Arthritis
Dermatomyositis
Polyarthritis
Systemic Lupus Erythematosis
Vasculitis
Glucocorticoid-induced Osteoporosis
Keywords: denosumab
pediatric
rheumatology
osteoporosis
glucocorticoid
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2015-04-16
Enrollment: 0
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The purpose of this study is to evaluate denosumab as a novel treatment for bone loss in children treated with glucocorticoids for rheumatic disorders. Children with rheumatic disorders are at risk for low bone density and fractures from the inflammatory effects of the underlying disease, and also from direct effects of glucocorticoids on bone. 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 BMD in children with rheumatic disorders, age 4 to 16 years, recruited within 1 month of starting a chronic systemic glucocorticoid regimen. Two different sequential doses will be administered to the intervention group and evaluation for safety and efficacy will be conducted at study visits. 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.

Eligibility criteria: Inclusion Criteria:

1. Age 4 to 16 years of age.
2. 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.
3. Within 1 month of initiating glucocorticoids ≥0.5 mg/kg prednisone equivalent daily, planned for ≥ 6 months.
4. BMD by DXA with Z-score \< 0.0 on screening at lumbar spine or total body less head (TBLH).

Exclusion Criteria:

1. Previous treatment with a bisphosphonate, or other osteoporosis medication.
2. Metabolic bone disorders besides glucocorticoid-induced osteoporosis; other disorders treated with systemic glucocorticoids (inflammatory bowel disease, severe pulmonary disease, nephrotic syndrome, etc.).
3. Intent to treat with a tumor necrosis factor inhibitor or Interleukin 6 receptor antagonist during the first 6 months.
4. Glomerular filtration rate \< 30ml/min \[pediatric estimated glomerular filtration rate = 0.413\*(height/serum creatinine)\] 75
5. Planned orthopedic or other major surgery during the course of the study (at the time of enrollment)
6. Significant dental caries, or plans to undergo invasive oral procedures during the subsequent 12 months.
7. Known allergy to latex (drug packaging includes a natural rubber stopper), fructose intolerance or other denosumab contraindication.
8. 25-hydroxyvitamin D (25OHD) level \< 32 ng/dl. Subjects with 25OHD \<32 ng/ml may be given cholecalciferol and rescreened.
9. Hypocalcemia at screening (total serum calcium \< 8.5 mg/dl after correction for albumin level).
10. Chronic ventilator dependence, or other conditions increasing risk of participation.
11. Pregnancy, or refusal to use acceptable contraception or abstain during the protocol (post-pubertal female).

Primary outcomes:
measure: Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio).
timeFrame: 2 weeks, 1 month, 2 month, 3 month after each dose day.
Secondary outcomes:
measure: The duration of suppression of the NTX/creatinine ratio
timeFrame: up to six months after each dose day
measure: The changes in bone specific alkaline phosphorus
timeFrame: From baseline to 1 week, 1,3,6 months after each dose day
measure: Changes of BMD spine Z-scores
timeFrame: 12 month
measure: Changes of BMD Total body less head (TBLH) Z-scores
timeFrame: 12 month
measure: Changes of volumetric BMD on peripheral quantitative computed tomography
timeFrame: 12 month
measure: Changes of polar strength-strain index at tibia
timeFrame: 12 month
measure: Changes of polar strength-strain index at radius
timeFrame: 12 month
measure: Changes in bone strength index for compression at tibia.
timeFrame: 12 month
measure: Changes in bone strength index for compression at radius
timeFrame: 12 month
measure: The relationships of Interleukin 6 to baseline NTX/creatinine ratio
timeFrame: baseline visit
measure: The relationships of Interleukin 6 to baseline DXA
timeFrame: baseline visit
measure: The relationships of Interleukin 6 to baseline pQCT variables.
timeFrame: baseline visit
measure: The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio
timeFrame: baseline visit
measure: The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD
timeFrame: baseline visit
measure: The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD
timeFrame: baseline visit
measure: Dose limiting toxicities (DLTs), including hypocalcemia
timeFrame: 3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits.
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
Study officials:
affiliation: Indiana University
name: Erik Imel, MD
role: PRINCIPAL_INVESTIGATOR
References: