Granulomatosis With PolyangiitisPhase 4NCT04944524
Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA
A Phase 4 study testing Tofacitinib and Methotrexate in people with Granulomatosis With Polyangiitis, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Granulomatosis With Polyangiitis
- What is being tested?
- Tofacitinib and Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2021to 1 Jul 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Rheumatology in Zhongshan hospital, Fudan University
Shanghai, Shanghai Municipality, 200032
Lindi Jiang, PhD, +86-021-64041990, zsh-rheum@hotmail.com
About this study
Official title: Randomized Trial of Tofacitinib Versus Methotrexate for Maintenance Therapy in Granulomatosis With Polyangiitis
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.
Read the 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
- Being tested
- Tofacitinib, Methotrexate
- Medical subject headings
- Granulomatosis with Polyangiitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofacitinibDrug
Also called Tof
- 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.
MethotrexateDrug
Also called MTX
- 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.)
Measured: From the enrollment to the the end of 12 month.
Secondary outcomes (4)
Time to first relapse.
The time period from the baseline to the time when the first relapse occurred.
Measured: From the enrollment to the the end of 12 month.
Number of relapse
Total times of relapse during the whole period of 12-month follow-up.
Measured: From the enrollment to the the end of 12 month.
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.
Measured: From the enrollment to the the end of 12 month.
Adverse events
All the kinds of adverse event related to the treatment and the disease itself will be recorded.
Measured: From the enrollment to the the end of 12 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2021
- Study start1 Jul 2021
- Primary completion1 Jul 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Granulomatosis With PolyangiitisStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lindi Jiang, PhD, Study chair, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04944524
- Sponsor's protocol ID
- TofMTX-GPA maintain
- Status last verified
- Jun 2021
- First submitted
- 22 Jun 2021
- Last updated
- 9 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Tofacitinib Versus Methotrexate for Maintenance Therapy in Granulomatosis With Polyangiitis
- ClinicalTrials.gov ID
- NCT04944524
- Acronym / sponsor ID
- TofMTX-GPA maintain
- Conditions
- Granulomatosis With Polyangiitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 1 Jul 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 29 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tofactitinib | Experimental | Drug: Tofacitinibpartcipants 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. |
| Methotrexate | Active comparator | Drug: Methotrexatepartcipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TofacitinibAlso: Tof1. 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. | Drug | Tofactitinib |
| MethotrexateAlso: MTX1. 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. | Drug | Methotrexate |
Primary outcome
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.)
4 secondary outcomes
Time to first relapse.
Time frame: From the enrollment to the the end of 12 month.
Number of relapse
Time frame: From the enrollment to the the end of 12 month.
Cumulative dosage of corticosteroids
Time frame: From the enrollment to the the end of 12 month.
Adverse events
Time frame: From the enrollment to the the end of 12 month.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindi Jiang, PhD study chair
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tofacitinib and Methotrexate in people with Granulomatosis With Polyangiitis, run by Shanghai Zhongshan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lindi Jiang, PhD (+8602164041990 ext. 2471, zsh-rheum@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse rate (major or minor) at 12 months (time frame: From the enrollment to the the end of 12 month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2021.