Effect of Denosumab in Erosion Healing in RA

Study Overview
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Brief Summary
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To evaluate the effects of denosumab on erosion healing and change in physical function in RA patients.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study, which aimed to evaluate the effects of denosumab on erosion healing and change in physical function in rheumatoid arthritis (RA) patients in low-disease activity or remission receiving synthetic DMARDs (sDMARDs) treatment using High-resolution peripheral quantitative CT (HR-pQCT).

Official Title
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Effect of RANKL Inhibition on Healing of Bone Erosion in Rheumatoid Arthritis Using HR-pQCT

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Denosumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old DAS28 ≤5.1 without severe deformity in MCP joints which would influence the longitudinal assessment of HR-pQCT Exclusion Criteria: RA functional status class IV (limited in ability to perform usual self-care, vocational, and avocational activities) treatment with any biologic DMARDs for RA treatment within 8 weeks before randomisation pregnancy or premenopausal women planning pregnancy previous use of denosumab, zoledronic acid or teriparatide Hyperparathyroidism contraindications to denosumab Bisphosphonate, biologic DMARDs and the use of oral glucocorticoid >10 mg/day (prednisolone equivalent)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denosumab<br>Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months). | Drug: Denosumab<br>* Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).<br>|
| Placebo Comparator: Placebo<br>Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months). | Other: Placebo<br>* Subcutaneous injections of placebo (0.9% Sodium Chloride solution) will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4 | 1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of > SDC in osteosclerosis at the margin of erosion. | 12 months | 
| The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4 | 1). A decrease in erosion volume of ≥ smallest detectable change (SDC) from baseline, and 2). The presence of > SDC in osteosclerosis at the margin of erosion. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erosion progression | Changes in size of erosion (depth, width and volume) and marginal osteosclerosis (semi-quantitative and quantitative) using HR-pQCT | 12 and 24 month | 
| Radiographic progression | Radiographic progression expressed by changes in van der Heijde-Sharp score on radiograph | 12 and 24 months | 
| Change in various patient-reported outcomes | Changes in physical function (HAQ) will be measured | 12 and 24 month | 
| Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ | Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ will be analysed | 24 month | 
| Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT | Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT | 12 and 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, HR-pQCT, erosion, denosumab