Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

NCT ID: NCT04944524

Last Updated: 2021-07-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2024-07-01

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.

Conditions

Granulomatosis With Polyangiitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tofacitinib

Intervention Type: DRUG

1. Tofacitinib 5mg twice a day for 12months;

2. 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.

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.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

1. Methotrexate (15 mg/week initially and progressively increased every week by 2.5 mg, to a maximum and optimal dose of 20 mg/week)

2. 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.

Interventions

Tofacitinib

1. Tofacitinib 5mg twice a day for 12months;

2. 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.

Intervention Type: DRUG

Methotrexate

1. Methotrexate (15 mg/week initially and progressively increased every week by 2.5 mg, to a maximum and optimal dose of 20 mg/week)

2. 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.

Intervention Type: DRUG

Other Intervention Names

Tof; MTX

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindi Jiang, PhD

Role: STUDY_CHAIR

Fudan University

Locations

Department of Rheumatology in Zhongshan hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lindi Jiang, PhD

Role: CONTACT

zsh-rheum@hotmail.com

+8602164041990 ext. 2471

Yun Liu, PhD

Role: CONTACT

chenry825@hotmail.com

+8602164041990 ext. 2471

Facility Contacts

Lindi Jiang, PhD

Role: primary

zsh-rheum@hotmail.com

+86-021-64041990

Other Identifiers

TofMTX-GPA maintain

Identifier Type: -

Identifier Source: org_study_id