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Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

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ClinicalTrials.gov Identifier: NCT04944524
Recruitment Status : Recruiting
First Posted : June 29, 2021
Last Update Posted : July 9, 2021
Sponsor:
Information provided by (Responsible Party):
Shanghai Zhongshan Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Granulomatosis With Polyangiitis Drug: Tofacitinib Drug: Methotrexate Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Tofacitinib Versus Methotrexate for Maintenance Therapy in Granulomatosis With Polyangiitis
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : July 1, 2024

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Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: 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.
Other Name: Tof
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.
 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.
Other Name: MTX


Outcome Measures
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Primary Outcome Measures :
  1. Relapse rate (major or minor) at 12 months [ Time Frame: From the enrollment to the the end of 12 month. ]
    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.)


Secondary Outcome Measures :
  1. Time to first relapse. [ Time Frame: From the enrollment to the the end of 12 month. ]
    The time period from the baseline to the time when the first relapse occurred.

  2. Number of relapse [ Time Frame: From the enrollment to the the end of 12 month. ]
    Total times of relapse during the whole period of 12-month follow-up.

  3. Cumulative dosage of corticosteroids [ Time Frame: From the enrollment to the the end of 12 month. ]
    The cumulative dosage of corticosteroids during the whole period of 12-month follow-up. The cumulative dosage = Sum of different dose of prednisone every day.

  4. Adverse events [ Time Frame: From the enrollment to the the end of 12 month. ]
    All the kinds of adverse event related to the treatment and the disease itself will be recorded.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04944524


Contacts
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Contact: Lindi Jiang, PhD +8602164041990 ext 2471 zsh-rheum@hotmail.com
Contact: Yun Liu, PhD +8602164041990 ext 2471 chenry825@hotmail.com

Locations
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China, Shanghai
Department of Rheumatology in Zhongshan hospital, Fudan University Recruiting
Shanghai, Shanghai, China, 200032
Contact: Lindi Jiang, PhD    +86-021-64041990    zsh-rheum@hotmail.com   
Sponsors and Collaborators
Shanghai Zhongshan Hospital
Investigators
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Study Chair: Lindi Jiang, PhD Fudan University
More Information
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Responsible Party: Shanghai Zhongshan Hospital
ClinicalTrials.gov Identifier: NCT04944524    
Other Study ID Numbers: TofMTX-GPA maintain
First Posted: June 29, 2021    Key Record Dates
Last Update Posted: July 9, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Granulomatosis with Polyangiitis
Systemic Vasculitis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
 Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors