Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

NCT04944524 | Unknown Phase 4 DMC

• 1 other identifier: TofMTX-GPA maintain
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Granulomatosis With Polyangiitis

Outcome Measures

Primary Outcomes (1)

• Relapse rate (major or minor) at 12 months

  The major or minor relapse rate equals to the patients with relapse/ total participants ( A major relapse should be defined as the re-occurrence or new onset of potentially organ- or life-threatening disease activity that cannot be treated with an increase of GC alone and requires further escalation of treatment. All other relapses should be classified as minor.)

  From the enrollment to the the end of 12 month.

Secondary Outcomes (4)

• Time to first relapse.

  From the enrollment to the the end of 12 month.

• Number of relapse

  From the enrollment to the the end of 12 month.

• Cumulative dosage of corticosteroids

  From the enrollment to the the end of 12 month.

• Adverse events

  From the enrollment to the the end of 12 month.

Study Arms (2)

Tofactitinib

EXPERIMENTAL

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.

Drug: Tofacitinib

Methotrexate

ACTIVE COMPARATOR

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.

Drug: Methotrexate

Interventions

Tofacitinib 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.

Also known as: Tof

Tofactitinib

Methotrexate 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.

Also known as: MTX

Methotrexate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed or relapsing Granulomatosis with polyangiitis met the criteria of 1990 ACR and 2012 Chapel Hill criteria
• Patients in disease flare have achieved remission using a treatment combining corticosteroids and IV cyclophosphamide
• 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
• Age 18 to 75 years
• Written informed consent obtained before taking part in the study

You may not qualify if:

• 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.)
• Serum creatinine\>120umol/L or proteinuria\>1.0g/d
• Failure to response after treatment with methotrexate or cyclophosphamide previously
• Receipt of a JAKi therapy previously
• Co-existence of another systemic autoimmune disease
• Secondary vasculitis (following neoplastic disease, an infection or antithyroid drugs)
• Malignancy or history of malignancy
• Infection by HIV, HCV, HBV or tuberculosis
• Severe uncontrolled cardiovascular, pulmonary, liver, gastrointestinal, endocrine, hematological, neurological, or psychiatric diseases that are not related to systemic vasculitis
• Allergic to any of the medication (cyclophosphamide, corticosteroids, tofacitinib, methotrexate)
• 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
• 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.
• Incapacity or refusal to understand or sign the informed consent form.
• Pregnancy, breastfeeding.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Department of Rheumatology in Zhongshan hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Granulomatosis with Polyangiitis

Interventions

tofacitinib; Methotrexate

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lindi Jiang, PhD

  Fudan University

  STUDY CHAIR

Central Study Contacts

Lindi Jiang, PhD

CONTACT

+8602164041990; zsh-rheum@hotmail.com

Yun Liu, PhD

CONTACT

+8602164041990; chenry825@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2021
• First Posted: June 29, 2021
• Study Start: July 1, 2021
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: July 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)