Effect of Denosumab in Erosion Healing in RA

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Denosumab; Other: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Department of Medicine and Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Denosumab; Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).	Drug: Denosumab; Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
Placebo Comparator: Placebo; 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; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Publications and helpful links

General Publications

• So H, Cheng IT, Lau SL, Chow E, Lam T, Hung VW, Li EK, Griffith JF, Lee VW, Shi L, Huang J, Kwok KY, Yim CW, Li TK, Lo V, Lee J, Lee JJ, Qin L, Tam LS. Effects of RANKL inhibition on promoting healing of bone erosion in rheumatoid arthritis using HR-pQCT: a 2-year, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2021 Aug;80(8):981-988. doi: 10.1136/annrheumdis-2021-219846. Epub 2021 Apr 2.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Actual): May 24, 2020
• Study Completion (Actual): May 24, 2020

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): November 24, 2020
• Last Update Submitted That Met QC Criteria: November 23, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; HR-pQCT; denosumab; erosion
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: RA-RANKL-2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes