Effect of Denosumab in Erosion Healing in RA
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Denosumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, HR-pQCT, erosion, denosumab
Eligibility Criteria
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)
Sites / Locations
- Department of Medicine and Therapeutics
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Denosumab
Placebo
Arm Description
Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
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).
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Erosion progression
Changes in size of erosion (depth, width and volume) and marginal osteosclerosis (semi-quantitative and quantitative) using HR-pQCT
Radiographic progression
Radiographic progression expressed by changes in van der Heijde-Sharp score on radiograph
Change in various patient-reported outcomes
Changes in physical function (HAQ) will be measured
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
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
Full Information
NCT ID
NCT03239080
First Posted
August 1, 2017
Last Updated
November 23, 2020
Sponsor
Chinese University of Hong Kong
1. Study Identification
Unique Protocol Identification Number
NCT03239080
Brief Title
Effect of Denosumab in Erosion Healing in RA
Official Title
Effect of RANKL Inhibition on Healing of Bone Erosion in Rheumatoid Arthritis Using HR-pQCT
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
June 19, 2017 (Actual)
Primary Completion Date
May 24, 2020 (Actual)
Study Completion Date
May 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the effects of denosumab on erosion healing and change in physical function in RA patients.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, HR-pQCT, erosion, denosumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denosumab
Arm Type
Active Comparator
Arm Description
Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Denosumab
Intervention Description
Subcutaneous injections of denosumab 60mg will be given in 4 doses at each visit (at baseline, 6, 12 and 18 months).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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).
Primary Outcome Measure Information:
Title
The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4
Description
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.
Time Frame
12 months
Title
The percentage of patients with erosion healing determined using HR-pQCT on MCP 2-4
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Erosion progression
Description
Changes in size of erosion (depth, width and volume) and marginal osteosclerosis (semi-quantitative and quantitative) using HR-pQCT
Time Frame
12 and 24 month
Title
Radiographic progression
Description
Radiographic progression expressed by changes in van der Heijde-Sharp score on radiograph
Time Frame
12 and 24 months
Title
Change in various patient-reported outcomes
Description
Changes in physical function (HAQ) will be measured
Time Frame
12 and 24 month
Title
Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ
Description
Association between the changes in erosion size on HR-pQCT, van der Heijde-Sharp score on radiograph and HAQ will be analysed
Time Frame
24 month
Title
Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT
Description
Changes in joint space width (minimal, maximal, asymmetry and distribution) using HR-pQCT
Time Frame
12 and 24 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai Shan Tam, MD
Organizational Affiliation
Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Medicine and Therapeutics
City
Hong Kong
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
33811034
Citation
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.
Results Reference
derived
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Effect of Denosumab in Erosion Healing in RA
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