Clinical trial NCT04799262: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polymyalgia Rheumatica
Effect of Drug
Safety Issues
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2021-03-16
Enrollment: 14
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Female or male between 50 and 85 years old.
2. PMR according to the ACR/ EULAR 2012 PMR classification criteria.
3. 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.
4. Patient is willing and able to take prednisone of 15 mg/day at baseline.
5. Signed written informed consent.

Exclusion Criteria:

1. 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.
2. Concurrent diagnosis of active fibromyalgia, rhabdomyolysis or neuropathic muscular diseases.
3. Organ transplant recipient.
4. 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.
5. 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.
6. Patients with a history of active or recurrent herpes zoster.
7. Patients who have had surgery within 4 weeks of screening or planned surgery during study.
8. Malignancy within 5 years prior to screening, except for non-melanoma skin cancer.
9. Pregnant or breastfeeding woman.
10. Any medical condition that could interfere with the implementation or interpretation of the study or with the safety of the patient during the study.

Primary outcomes:
measure: Response to treatment
timeFrame: 24 week
Secondary outcomes:
measure: Time till GC-free low disease activity within 24w
timeFrame: 24 week
measure: Time till first relapse within 24w
timeFrame: 24 week
measure: Cumulative GC dose at 24w
timeFrame: 24 week
measure: Proportion of patients with sustained remission with GC independence for 4 weeks from week 20
timeFrame: 24 week
measure: Incidence of adverse events (AEs) and Serious AEs (SAEs)
timeFrame: 24 week
measure: Change of disease activity by PMR-AS
timeFrame: 24 week
measure: Assessment of quality of life using the MHAQ
timeFrame: 24 week
measure: Assessment of quality of life using the EQ-5D
timeFrame: 24 week
measure: Circulating serum cytokines, immunoregulators, and inflammatory parameters
timeFrame: 24 week
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ren Ji Hospital
Study officials:
affiliation: RenJi Hospital
name: Ting Li, MD
role: STUDY_CHAIR
References: