Brief Title
Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA
Official Title
Randomized Trial of Tofacitinib Versus Methotrexate for Maintenance Therapy in Granulomatosis With Polyangiitis
Brief Summary
The aim of this study is to identify the optimal maintenance therapy for granulomatosis with polyangiitis (GPA) by comparing the MTX (standard regimen) with Tofacitinib in terms of efficacy, i.e. in preventing relapses.
Detailed Description
Granulomatosis with polyangiitis (GPA), a systemic small-vessel vasculitis, could involve multiple tissues and organs. Remission of GPA can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent and remain a challenge. The optimal drug for maintenance treatment is not determined. Tofacitinib is a Jak inhibitor which has been proved to be effective in multiple inflammatory diseases such as rheumatoid arthritis. But the efficiency and safety of tofacitinib in treating GPA remains unclear yet. In the present randomized trial, the comparison of MTX (standard regimen) with Tofacitinib in terms of efficacy, i.e. in preventing relapses will be conducted.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Relapse rate (major or minor) at 12 months
Secondary Outcome
Time to first relapse.
Condition
Granulomatosis With Polyangiitis
Intervention
Tofacitinib
Study Arms / Comparison Groups
Tofactitinib
Description: partcipants would be given one tablet of tofacitinib (5mg per tablet), twice per day, the treatment duration will last 12 months during the whole follow-up period.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
66
Start Date
July 1, 2021
Completion Date
July 1, 2024
Primary Completion Date
July 1, 2024
Eligibility Criteria
Inclusion Criteria: 1. Patients with newly diagnosed or relapsing Granulomatosis with polyangiitis met the criteria of 1990 ACR and 2012 Chapel Hill criteria 2. Patients in disease flare have achieved remission using a treatment combining corticosteroids and IV cyclophosphamide 3. Remission is defined as a Birmingham Vasculitis Activity/ Wegener's granulomatosis (BVAS/WG) score of 0 and receiving 10 mg/day of oral prednisone (or equivalent) at least 2 weeks 4. Age 18 to 75 years 5. Written informed consent obtained before taking part in the study Exclusion Criteria: 1. Severe GPA defined as potentially organ- or life-threatening disease (i.e. alveolar haemorrhage, heart failure caused by myocarditis or pericarditis, progressive neurological symptoms, deaf, blindness, et al.) 2. Serum creatinine>120umol/L or proteinuria>1.0g/d 3. Failure to response after treatment with methotrexate or cyclophosphamide previously 4. Receipt of a JAKi therapy previously 5. Co-existence of another systemic autoimmune disease 6. Secondary vasculitis (following neoplastic disease, an infection or antithyroid drugs) 7. Malignancy or history of malignancy 8. Infection by HIV, HCV, HBV or tuberculosis 9. Severe uncontrolled cardiovascular, pulmonary, liver, gastrointestinal, endocrine, hematological, neurological, or psychiatric diseases that are not related to systemic vasculitis 10. Allergic to any of the medication (cyclophosphamide, corticosteroids, tofacitinib, methotrexate) 11. Blood dyscrasias including confirmed: Hemoglobin <9 g/dL or Hematocrit <30%; White blood cell count <3.0 x 109/L; Absolute neutrophil count <1.5 x 109/L; Platelet count <100 x 109/L; Alanine transaminase or aspartate aminotransferase or total bilirubin>1.5 upper normal limit; Estimated glomerular filtration rate<60ml/min/1.73m2 12. Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect. 13. Incapacity or refusal to understand or sign the informed consent form. 14. Pregnancy, breastfeeding.
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Lindi Jiang, PhD, +8602164041990, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04944524
Organization ID
TofMTX-GPA maintain
Responsible Party
Sponsor
Study Sponsor
Shanghai Zhongshan Hospital
Study Sponsor
Lindi Jiang, PhD, Study Chair, Fudan University
Verification Date
June 2021