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Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders

Primary Purpose

Osteoporosis, Juvenile Rheumatoid Arthritis, Dermatomyositis

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

denosumab

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring denosumab, pediatric, rheumatology, osteoporosis, glucocorticoid

Eligibility Criteria

4 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).

Exclusion Criteria:

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.
25-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).

Sites / Locations

Indiana University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Denosumab

No drug intervention

Arm Description

These subjects will receive two sequential doses of denosumab

These subjects do not receive denosumab

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The duration of suppression of the NTX/creatinine ratio

The changes in bone specific alkaline phosphorus

Changes of BMD spine Z-scores

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

Changes of volumetric BMD on peripheral quantitative computed tomography

Changes of polar strength-strain index at tibia

Changes of polar strength-strain index at radius

Changes in bone strength index for compression at tibia.

Changes in bone strength index for compression at radius

The relationships of Interleukin 6 to baseline NTX/creatinine ratio

The relationships of Interleukin 6 to baseline DXA

The relationships of Interleukin 6 to baseline pQCT variables.

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD

Dose limiting toxicities (DLTs), including hypocalcemia

Full Information

NCT ID

NCT02418273

First Posted

April 6, 2015

Last Updated

December 4, 2019

Sponsor

Indiana University

1. Study Identification

Unique Protocol Identification Number

NCT02418273

Brief Title

Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders

Official Title

Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders: a Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Withdrawn

Why Stopped

was not funded

Study Start Date

August 1, 2019 (Anticipated)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

denosumab, pediatric, rheumatology, osteoporosis, glucocorticoid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Denosumab

Arm Type

Experimental

Arm Description

These subjects will receive two sequential doses of denosumab

Arm Title

No drug intervention

Arm Type

No Intervention

Arm Description

These subjects do not receive denosumab

Intervention Type

Drug

Intervention Name(s)

denosumab

Other Intervention Name(s)

Prolia

Intervention Description

These subjects will receive two doses of denosumab.

Primary Outcome Measure Information:

Title

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

Time Frame

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

Secondary Outcome Measure Information:

Title

The duration of suppression of the NTX/creatinine ratio

Time Frame

up to six months after each dose day

Title

The changes in bone specific alkaline phosphorus

Time Frame

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

Title

Changes of BMD spine Z-scores

Time Frame

12 month

Title

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

Time Frame

12 month

Title

Changes of volumetric BMD on peripheral quantitative computed tomography

Time Frame

12 month

Title

Changes of polar strength-strain index at tibia

Time Frame

12 month

Title

Changes of polar strength-strain index at radius

Time Frame

12 month

Title

Changes in bone strength index for compression at tibia.

Time Frame

12 month

Title

Changes in bone strength index for compression at radius

Time Frame

12 month

Title

The relationships of Interleukin 6 to baseline NTX/creatinine ratio

Time Frame

baseline visit

Title

The relationships of Interleukin 6 to baseline DXA

Time Frame

baseline visit

Title

The relationships of Interleukin 6 to baseline pQCT variables.

Time Frame

baseline visit

Title

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline NTX/creatinine ratio

Time Frame

baseline visit

Title

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline BMD

Time Frame

baseline visit

Title

The relationships of receptor activator of nuclear factor-kappa B ligand (RANKL) to baseline volumetric BMD

Time Frame

baseline visit

Title

Dose limiting toxicities (DLTs), including hypocalcemia

Time Frame

3 days, 1 week, 2, week, month 3,4,5,6 after each dose; or any other visits.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). Exclusion Criteria: 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. 25-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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Erik Imel, MD

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

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Denosumab for Glucocorticoid-treated Children With Rheumatic Disorders

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