Ignite Creation Date:
2024-05-06 @ 7:17 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05955066
Status:
RECRUITING
Last Update Posted:
2024-02-07
First Post:
2023-07-12
Brief Title:
Effect of JAK Inhibitor on Erosion Healing in RA
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
Effect of JAK Inhibitor on Bone Erosion Repair in Rheumatoid Arthritis Assessed by HR-pQCT a Randomized Placebo-controlled Study
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Objective To investigate the effect of Janus kinase JAK inhibition by baricitinib on erosion healing in rheumatoid arthritis RA patients with active disease using high-resolution peripheral quantitative computer tomographyHR-pQCT
Hypothesis JAK inhibitor can lead to healing of existing erosion in RA patients with active disease
Design and subjects This is a 24-week randomized placebo-controlled double-blind study We plan to enroll 60 adult patients with active RA Disease activity score 28-C-reactive protein DAS28-CRP32 and 1 bone erosion on HR-pQCT They will be randomized 11 to receive JAK inhibitor baricitinib 4mg once daily or placebo for 24 weeks Medications will be adjusted according to a standard protocol aiming to achieve low disease activity Patients requiring biologic or other targeted synthetic disease-modifying-anti-rheumatic-drugs will be excluded
Study instruments HR-pQCT of the 2-4 metacarpophalangealMCP will be done at baseline and 24 weeks Inflammatory cytokine profile and bone cartilage interface biomarkers will also be checked at baseline and 24 weeks Clinical response will be monitored using DAS28-CRP
Main outcome measures and analysis The primary outcome is the proportion of patients with erosion volume regression on HR-pQCT comparing the two groups by chisquare test
Hypothesis JAK inhibitor can lead to healing of existing erosion in RA patients with active disease
Design and subjects This is a 24-week randomized placebo-controlled double-blind study We plan to enroll 60 adult patients with active RA Disease activity score 28-C-reactive protein DAS28-CRP32 and 1 bone erosion on HR-pQCT They will be randomized 11 to receive JAK inhibitor baricitinib 4mg once daily or placebo for 24 weeks Medications will be adjusted according to a standard protocol aiming to achieve low disease activity Patients requiring biologic or other targeted synthetic disease-modifying-anti-rheumatic-drugs will be excluded
Study instruments HR-pQCT of the 2-4 metacarpophalangealMCP will be done at baseline and 24 weeks Inflammatory cytokine profile and bone cartilage interface biomarkers will also be checked at baseline and 24 weeks Clinical response will be monitored using DAS28-CRP
Main outcome measures and analysis The primary outcome is the proportion of patients with erosion volume regression on HR-pQCT comparing the two groups by chisquare test
Detailed Description:
Rheumatoid arthritis RA is a common chronic inflammatory arthritis affecting 035 of the population in Hong Kong Uncontrolled arthritis can lead to joint destruction functional disability and decreased quality of life We also found that the disease carried substantial socioeconomic costs
Bone erosions are specific to RA reflecting disease severity and can be used to monitor disease progression In early RA functional capacity is most associated with disease activity but in established disease with joint damage A recent study also showed joint tenderness a crucial determinant of disease activity was associated with structural damage rather than sonographic synovitis in non-swollen joints in established RA In fact prevention of erosion on radiographs is used to define the efficacy of disease modifying anti-rheumatic drugs DMARDs in RA After all the ultimate aims of management in RA are to reduce symptoms preserve function and maintain quality of life
The 60 patients with erosion will be randomized in a 11 ratio to JAK1 inhibitor n30 or placebo n30 group Randomization will be performed using a computer-generated randomization list provided by the research pharmacist using a permuted blocks design with block sizes of 4 Allocation concealment will be ensured by the use of sequentially numbered opaque sealed envelopes Treatment will be masked to patients and investigators
All the participants will be instructed to take one study capsule 4 mg baricitinib or placebo daily for 24 weeks They will be treated to the target of DAS28 remission or low disease activity LDA at PWH throughout the study period according to a standard protocol modified to our study based on the EULAR recommendation and the Hong Kong guideline on the use of DMARDs Disease activity and adverse events will be monitored at 4 weeks 12 weeks and 24 weeks Patients will be advised to reach out to the rheumatologists earlier if the condition changes unexpectedly Changes in treatment eg the switching to a new csDMARD including leflunomide hydroxychloroquine or sulfasalazine or the dosage of csDMARDs and changes in the dosage or the addition of glucocorticoids or nonsteroidal anti-inflammatory drugs are allowed throughout the study The use of btsDMARDs bisphosphonates denosumab teriparatide or systemic glucocorticoid prednisolone 10 mgday equivalent will be prohibited throughout the study Participants who required rescue btsDMARDs will be withdrawn from the study and excluded from the final analysis
The following clinical variables will be assessed at each visit erythrocyte sedimentation rate ESR CRP number of swollen joints 0-28 number of tender joints 0-28 visual analogue scale VAS for pain 0-100 mmmost pain VAS for patients global assessment 0-100 mmworst score VAS for physicians global assessment 0-100 mmworst score and DAS28 score The number of damaged joints will be assessed at baseline and the end of the study Rheumatoid factor status and anti-cyclic citrullinated peptide antibodies status will be determined at baseline Functional disability is assessed by the disability index of HAQ 0-3most functional disability ACR205070 responses are defined as at least 20 50 and 70 improvement in swollen joint and tender joint counts and three of five other variables ie ESR or CRP HAQ score pain score and physicians and patients global assessments
Bone erosions are specific to RA reflecting disease severity and can be used to monitor disease progression In early RA functional capacity is most associated with disease activity but in established disease with joint damage A recent study also showed joint tenderness a crucial determinant of disease activity was associated with structural damage rather than sonographic synovitis in non-swollen joints in established RA In fact prevention of erosion on radiographs is used to define the efficacy of disease modifying anti-rheumatic drugs DMARDs in RA After all the ultimate aims of management in RA are to reduce symptoms preserve function and maintain quality of life
The 60 patients with erosion will be randomized in a 11 ratio to JAK1 inhibitor n30 or placebo n30 group Randomization will be performed using a computer-generated randomization list provided by the research pharmacist using a permuted blocks design with block sizes of 4 Allocation concealment will be ensured by the use of sequentially numbered opaque sealed envelopes Treatment will be masked to patients and investigators
All the participants will be instructed to take one study capsule 4 mg baricitinib or placebo daily for 24 weeks They will be treated to the target of DAS28 remission or low disease activity LDA at PWH throughout the study period according to a standard protocol modified to our study based on the EULAR recommendation and the Hong Kong guideline on the use of DMARDs Disease activity and adverse events will be monitored at 4 weeks 12 weeks and 24 weeks Patients will be advised to reach out to the rheumatologists earlier if the condition changes unexpectedly Changes in treatment eg the switching to a new csDMARD including leflunomide hydroxychloroquine or sulfasalazine or the dosage of csDMARDs and changes in the dosage or the addition of glucocorticoids or nonsteroidal anti-inflammatory drugs are allowed throughout the study The use of btsDMARDs bisphosphonates denosumab teriparatide or systemic glucocorticoid prednisolone 10 mgday equivalent will be prohibited throughout the study Participants who required rescue btsDMARDs will be withdrawn from the study and excluded from the final analysis
The following clinical variables will be assessed at each visit erythrocyte sedimentation rate ESR CRP number of swollen joints 0-28 number of tender joints 0-28 visual analogue scale VAS for pain 0-100 mmmost pain VAS for patients global assessment 0-100 mmworst score VAS for physicians global assessment 0-100 mmworst score and DAS28 score The number of damaged joints will be assessed at baseline and the end of the study Rheumatoid factor status and anti-cyclic citrullinated peptide antibodies status will be determined at baseline Functional disability is assessed by the disability index of HAQ 0-3most functional disability ACR205070 responses are defined as at least 20 50 and 70 improvement in swollen joint and tender joint counts and three of five other variables ie ESR or CRP HAQ score pain score and physicians and patients global assessments
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None