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Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04944524
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 4
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Shanghai Zhongshan Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Lindi Jiang, PhD
Principal Investigator Affiliation	Fudan University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Granulomatosis With Polyangiitis

Additional Details

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.

Arms & Interventions

Arms

Experimental: Tofactitinib

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.

Active Comparator: Methotrexate

partcipants would be given tablets of methotrexate (2.5mg per tablet) from the initial dose of 15mg (6 tablets) and add to the maximal and optimal dose of 20mg (8 tablets), once per week, the treatment duration will last 12 months during the whole follow-up period.

Interventions

Drug: - Tofacitinib

Tofacitinib 5mg twice a day for 12months; Basic treatment with prednisone. (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day. (2) Glucocorticoids tapering: after two weeks' usage of initial glucocorticoids dose, glucocorticoids can be tapered if there's no disease activity (BVAS/WG=0) or at least 50% reduction of BVAS/WG and no new manifestations. Prednisone (or equivalent) was reduced to 10mg/d at the time of randomization.

Drug: - Methotrexate

Methotrexate (15 mg/week initially and progressively increased every week by 2.5 mg, to a maximum and optimal dose of 20 mg/week) Basic treatment with prednisone. (1) the initial dose of prednisone (or equivalent): 0.8mg/kg/day. (2) Glucocorticoids tapering: after two weeks' usage of initial glucocorticoids dose, glucocorticoids can be tapered if there's no disease activity (BVAS/WG=0) or at least 50% reduction of BVAS/WG and no new manifestations. Prednisone (or equivalent) was reduced to 10mg/d at the time of randomization.

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