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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT02418273
Other study ID # 1504269855
Secondary ID
Status Withdrawn
Phase Phase 1/Phase 2
First received
Last updated
Start date August 1, 2019
Est. completion date June 2021

Study information

Verified date December 2019
Source Indiana University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date June 2021
Est. primary completion date June 2021
Accepts healthy volunteers No
Gender All
Age group 4 Years to 16 Years
Eligibility 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).

Study Design


Intervention

Drug:
denosumab
These subjects will receive two doses of denosumab.

Locations

Country Name City State
United States Indiana University School of Medicine Indianapolis Indiana

Sponsors (1)

Lead Sponsor Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Changes in bone turnover marker (N-telopeptide (NTX) /creatinine ratio). 2 weeks, 1 month, 2 month, 3 month after each dose day.
Secondary The duration of suppression of the NTX/creatinine ratio up to six months after each dose day
Secondary The changes in bone specific alkaline phosphorus From baseline to 1 week, 1,3,6 months after each dose day
Secondary Changes of BMD spine Z-scores 12 month
Secondary Changes of BMD Total body less head (TBLH) Z-scores 12 month
Secondary Changes of volumetric BMD on peripheral quantitative computed tomography 12 month
Secondary Changes of polar strength-strain index at tibia 12 month
Secondary Changes of polar strength-strain index at radius 12 month
Secondary Changes in bone strength index for compression at tibia. 12 month
Secondary Changes in bone strength index for compression at radius 12 month
Secondary The relationships of Interleukin 6 to baseline NTX/creatinine ratio baseline visit
Secondary The relationships of Interleukin 6 to baseline DXA baseline visit
Secondary The relationships of Interleukin 6 to baseline pQCT variables. baseline visit
Secondary The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio baseline visit
Secondary The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD baseline visit
Secondary The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD baseline visit
Secondary Dose limiting toxicities (DLTs), including hypocalcemia 3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits.
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