Back to resultsTofacitinib as a GC Sparing Agent for Polymyalgia Rheumatica
Primary Purpose
Polymyalgia Rheumatica, Effect of Drug, Safety Issues
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tofacitinib 5 MG
Sponsored by
About this trial
This is an interventional treatment trial for Polymyalgia Rheumatica
Eligibility Criteria
Inclusion Criteria:
- Female or male between 50 and 85 years old.
- PMR according to the ACR/ EULAR 2012 PMR classification criteria.
- Patients must have erythrocyte sedimentation rate (ESR) ≥20 mm/hr and/or CRP ≥8 mg/L associated with highly active PMR (PMR-AS>17) within 2 weeks prior to screening.
- Patient is willing and able to take prednisone of 15 mg/day at baseline.
- Signed written informed consent.
Exclusion Criteria:
- Presence of any other connective tissue disease, such as but not limited to giant-cell arteritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis.
- Concurrent diagnosis of active fibromyalgia, rhabdomyolysis or neuropathic muscular diseases.
- Organ transplant recipient.
- Any prior (within the defined period below) or concurrent use of immunosuppressive therapies but not limited to any of the following: ① Any prior use of tumor necrosis factor inhibitors, anti-IL-6 agents or JAK inhibitor; ② Alkylating agents including cyclophosphamide within 6 months of baseline; ③ Cell-depletion agents (e.g. anti-CD20) without evidence of recovery of B cells to baseline level; ④ Abatacept within 8 weeks of baseline; ⑤ Any prior use of csDMARDs at unstable dose for less than 12 weeks before baseline, e.g. cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, MTX; ⑥ Concurrent use of systemic GCs for conditions other than PMR.
- Evidence (as assessed by the investigators) of active infection, such as presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody in blood, human immunodeficiency virus (HIV) positivity.
- Patients with a history of active or recurrent herpes zoster.
- Patients who have had surgery within 4 weeks of screening or planned surgery during study.
- Malignancy within 5 years prior to screening, except for non-melanoma skin cancer.
- Pregnant or breastfeeding woman.
- Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.
Sites / Locations
- Ren Ji Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tofacitinib+Prednisone
Arm Description
Tofacitinib was given at the dose of 10mg daily through the 24 weeks. Prednisone (or equivalent oral GCs) of 15 mg daily at baseline willed be tapered to 2.5 mg or less within 20 weeks. Unless specifically considered by patients and physicians, the GC will be tapered followed the predefined taper regimen depending on the response to treatment judged by PMR-AS. The PMR-AS will be determined every two weeks; if<10 the GC daily dosage was decreased by 2.5mg; if>17, the GC daily dosage was increased to the previous dosage; if 10≤PMR-AS≤17, the GC daily dosage was maintained at the previous stable dose.
Outcomes
Primary Outcome Measures
Response to treatment
Response to treatment is defined as the achievement of sustained low disease activity (PMR-AS<7) with GC independence (≤2.5mg/d) for 4 weeks from week 20
Secondary Outcome Measures
Time till GC-free low disease activity within 24w
Time till GC-free low disease activity (PMR-AS<7) within 24 weeks
Time till first relapse within 24w
Time till first relapse (PMR-AS ≥7) within 24w
Cumulative GC dose at 24w
Cumulative glucocorticoids dose over time
Proportion of patients with sustained remission with GC independence for 4 weeks from week 20
Proportion of patients with sustained remission (PMR-AS <1.5) with GC independence (≤2.5mg/d) for 4 weeks from week 20
Incidence of adverse events (AEs) and Serious AEs (SAEs)
Incidence of adverse events (AEs) and Serious AEs (SAEs) within 24 weeks
Change of disease activity by PMR-AS
Change of disease activity by PMR-AS within 24 weeks
Assessment of quality of life using the MHAQ
The Modified Health Assessment Questionnaire (MHAQ), reduced the number of items from 20 in the original HAQ to eight, and improved the feasibility in clinical practice when screening patients. The MHAQ score is calculated as the mean of the scores for each activity. Total score is between 0.0-3.0, in 0.125 increments. Higher scores indicate worse function and greater disability. MHAQ scores <0.3 are considered normal.
Assessment of quality of life using the EQ-5D
Health quality assessed by EuroQol five dimensions questionnaire. It is a preference-based measure that can be regarded as a continuous outcome scored on a -0.59 to 1.00 scale, with 1.00 indicating 'full health' and 0 representing dead.
Circulating serum cytokines, immunoregulators, and inflammatory parameters
On the circulating serum cytokines, immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130, etc.), B cells receptors, phenotype of circulating T- and B-cells will be collected at W0 and W24. On inflammatory parameters (CRP and ESR) every 4 weeks from baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04799262
Brief Title
Tofacitinib as a GC Sparing Agent for Polymyalgia Rheumatica
Official Title
Phase II Study of Efficacy and Safety of Tofacitinib in Patients With Polymyalgia Rheumatica
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
March 16, 2022 (Actual)
Study Completion Date
May 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RenJi Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Glucocorticoids are the cornerstone treatment for polymyalgia rheumatica but induce adverse events. The efficacy of the candidate drug Tofacitinib has not yet been demonstrated in controlled studies. The aim of the study is to investigate the efficacy and safety of Tofacitinib as a glucocorticoid sparing agent in patients with polymyalgia rheumatica.
Detailed Description
A two-stage, phase 2 clinical trial was conducted to test whether tofacitinib would take into effect as a glucocorticoid sparing agent in patients with polymyalgia rheumatica. Tofacitinib was given at the dose of 10mg daily through the 24 weeks. Patients were to receive prednisone in a dosage of 15mg daily (or equivalent oral GCs) at baseline and tapered to 2.5mg or less daily within 20 weeks. The primary endpoint was the response to treatment, defined as the achievement of sustained low disease activity (PMR-AS<7) with GC independence (prednisone≤2.5mg daily or equivalent oral GCs) for 4 weeks from week 20.
The trial will be conducted following a two-stage Simon minimax design. After 8 participants have completed their 24-week follow up there will be an interim analysis. If there are 3 or more failures out of these 8 then the trial will stop with the conclusion that the study of Tofacitinib should be abandoned. If there are fewer than 3 failures then the study will continue until a further 6 participants have received treatment, giving a total sample size of 14. If amongst these 14 participants there are 4 or more failures then it will be concluded that further study of Tofacitinib should be abandoned. If further study of the drug is not abandoned at either the interim of the final analysis, then a recommendation to conduct a comparative, randomized phase III trial will be made.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyalgia Rheumatica, Effect of Drug, Safety Issues
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
Assessor and data analyst blindness. To avoid bias, physicians who assess disease activity will be blinded. Participants are required not to discuss their treatment regimen with physicians at each visit. The success of the blind method will be judged by requiring the assessors to determine the therapy of participants after each visit. When the database is locked, the statistician will carry on the data analysis in the hidden of therapy.
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tofacitinib+Prednisone
Arm Type
Experimental
Arm Description
Tofacitinib was given at the dose of 10mg daily through the 24 weeks. Prednisone (or equivalent oral GCs) of 15 mg daily at baseline willed be tapered to 2.5 mg or less within 20 weeks. Unless specifically considered by patients and physicians, the GC will be tapered followed the predefined taper regimen depending on the response to treatment judged by PMR-AS. The PMR-AS will be determined every two weeks; if<10 the GC daily dosage was decreased by 2.5mg; if>17, the GC daily dosage was increased to the previous dosage; if 10≤PMR-AS≤17, the GC daily dosage was maintained at the previous stable dose.
Intervention Type
Drug
Intervention Name(s)
Tofacitinib 5 MG
Other Intervention Name(s)
Prednisone
Intervention Description
Oral tofacitinib at the dose of 5mg twice a day was given for 24 weeks. Prednisone (or equivalent oral GCs) of 15 mg daily at baseline willed be tapered to 2.5 mg or less within 20 weeks. Unless specifically considered by patients and physicians, the GC will be tapered followed the predefined taper regimen depending on the response to treatment judged by PMR-AS. The PMR-AS will be determined every two weeks; if<10 the daily GC dosage was decreased by 2.5mg; if>17, the GC daily dosage was increased to the previous dosage; if 10≤PMR-AS≤17, the GC daily dosage was maintained at the previous stable dose.
Primary Outcome Measure Information:
Title
Response to treatment
Description
Response to treatment is defined as the achievement of sustained low disease activity (PMR-AS<7) with GC independence (≤2.5mg/d) for 4 weeks from week 20
Time Frame
24 week
Secondary Outcome Measure Information:
Title
Time till GC-free low disease activity within 24w
Description
Time till GC-free low disease activity (PMR-AS<7) within 24 weeks
Time Frame
24 week
Title
Time till first relapse within 24w
Description
Time till first relapse (PMR-AS ≥7) within 24w
Time Frame
24 week
Title
Cumulative GC dose at 24w
Description
Cumulative glucocorticoids dose over time
Time Frame
24 week
Title
Proportion of patients with sustained remission with GC independence for 4 weeks from week 20
Description
Proportion of patients with sustained remission (PMR-AS <1.5) with GC independence (≤2.5mg/d) for 4 weeks from week 20
Time Frame
24 week
Title
Incidence of adverse events (AEs) and Serious AEs (SAEs)
Description
Incidence of adverse events (AEs) and Serious AEs (SAEs) within 24 weeks
Time Frame
24 week
Title
Change of disease activity by PMR-AS
Description
Change of disease activity by PMR-AS within 24 weeks
Time Frame
24 week
Title
Assessment of quality of life using the MHAQ
Description
The Modified Health Assessment Questionnaire (MHAQ), reduced the number of items from 20 in the original HAQ to eight, and improved the feasibility in clinical practice when screening patients. The MHAQ score is calculated as the mean of the scores for each activity. Total score is between 0.0-3.0, in 0.125 increments. Higher scores indicate worse function and greater disability. MHAQ scores <0.3 are considered normal.
Time Frame
24 week
Title
Assessment of quality of life using the EQ-5D
Description
Health quality assessed by EuroQol five dimensions questionnaire. It is a preference-based measure that can be regarded as a continuous outcome scored on a -0.59 to 1.00 scale, with 1.00 indicating 'full health' and 0 representing dead.
Time Frame
24 week
Title
Circulating serum cytokines, immunoregulators, and inflammatory parameters
Description
On the circulating serum cytokines, immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130, etc.), B cells receptors, phenotype of circulating T- and B-cells will be collected at W0 and W24. On inflammatory parameters (CRP and ESR) every 4 weeks from baseline.
Time Frame
24 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female or male between 50 and 85 years old.
PMR according to the ACR/ EULAR 2012 PMR classification criteria.
Patients must have erythrocyte sedimentation rate (ESR) ≥20 mm/hr and/or CRP ≥8 mg/L associated with highly active PMR (PMR-AS>17) within 2 weeks prior to screening.
Patient is willing and able to take prednisone of 15 mg/day at baseline.
Signed written informed consent.
Exclusion Criteria:
Presence of any other connective tissue disease, such as but not limited to giant-cell arteritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis.
Concurrent diagnosis of active fibromyalgia, rhabdomyolysis or neuropathic muscular diseases.
Organ transplant recipient.
Any prior (within the defined period below) or concurrent use of immunosuppressive therapies but not limited to any of the following: ① Any prior use of tumor necrosis factor inhibitors, anti-IL-6 agents or JAK inhibitor; ② Alkylating agents including cyclophosphamide within 6 months of baseline; ③ Cell-depletion agents (e.g. anti-CD20) without evidence of recovery of B cells to baseline level; ④ Abatacept within 8 weeks of baseline; ⑤ Any prior use of csDMARDs at unstable dose for less than 12 weeks before baseline, e.g. cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, MTX; ⑥ Concurrent use of systemic GCs for conditions other than PMR.
Evidence (as assessed by the investigators) of active infection, such as presence of hepatitis B surface antigen (HBsAg) or hepatitis C antibody in blood, human immunodeficiency virus (HIV) positivity.
Patients with a history of active or recurrent herpes zoster.
Patients who have had surgery within 4 weeks of screening or planned surgery during study.
Malignancy within 5 years prior to screening, except for non-melanoma skin cancer.
Pregnant or breastfeeding woman.
Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ting Li, MD
Organizational Affiliation
RenJi Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Ren Ji Hospital
City
Shanghai
ZIP/Postal Code
201112
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Tofacitinib as a GC Sparing Agent for Polymyalgia Rheumatica
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