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Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

Primary Purpose

Granulomatosis With Polyangiitis

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Tofacitinib

Methotrexate

About this trial

This is an interventional treatment trial for Granulomatosis With Polyangiitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

Department of Rheumatology in Zhongshan hospital, Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tofactitinib

Methotrexate

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.)

Secondary Outcome Measures

Time to first relapse.

The time period from the baseline to the time when the first relapse occurred.

Number of relapse

Total times of relapse during the whole period of 12-month follow-up.

Cumulative dosage of corticosteroids

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.

Adverse events

All the kinds of adverse event related to the treatment and the disease itself will be recorded.

Full Information

NCT ID

NCT04944524

First Posted

June 22, 2021

Last Updated

July 5, 2021

Sponsor

Shanghai Zhongshan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04944524

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Recruiting

Study Start Date

July 1, 2021 (Actual)

Primary Completion Date

July 1, 2024 (Anticipated)

Study Completion Date

July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Zhongshan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Granulomatosis With Polyangiitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tofactitinib

Arm Type

Experimental

Arm 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.

Arm Title

Methotrexate

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tofacitinib

Other Intervention Name(s)

Tof

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

MTX

Intervention Description

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.

Primary Outcome Measure Information:

Title

Relapse rate (major or minor) at 12 months

Description

Time Frame

From the enrollment to the the end of 12 month.

Secondary Outcome Measure Information:

Title

Time to first relapse.

Description

The time period from the baseline to the time when the first relapse occurred.

Time Frame

From the enrollment to the the end of 12 month.

Title

Number of relapse

Description

Total times of relapse during the whole period of 12-month follow-up.

Time Frame

From the enrollment to the the end of 12 month.

Title

Cumulative dosage of corticosteroids

Description

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.

Time Frame

From the enrollment to the the end of 12 month.

Title

Adverse events

Description

All the kinds of adverse event related to the treatment and the disease itself will be recorded.

Time Frame

From the enrollment to the the end of 12 month.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lindi Jiang, PhD

Phone

+8602164041990

Ext

2471

zsh-rheum@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yun Liu, PhD

Phone

+8602164041990

Ext

2471

chenry825@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lindi Jiang, PhD

Organizational Affiliation

Fudan University

Official's Role

Study Chair

Facility Information:

Facility Name

Department of Rheumatology in Zhongshan hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lindi Jiang, PhD

Phone

+86-021-64041990

zsh-rheum@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA

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