Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis

• Register: JPRN
• Last refreshed on: 17 October 2023
• Main ID: JPRN-UMIN000024574
• Date of registration: 01/05/2017
• Prospective Registration: Yes
• Primary sponsor: Tokyo women's medical university Institute of rheumatology
• Public title: Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis
• Scientific title: Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis - AAVTCZ
• Date of first enrolment: 2018/07/02
• Target sample size: 48
• Recruitment status: Recruiting
• URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028278
• Study type: Interventional
• Study design: Parallel Randomized
• Phase: Phase II

Countries of recruitment

Japan

Contacts

• Name: Masayoshi Harigai
• Affiliation: Tokyo women's medical university Institute of Rheumatology

• Name: Michi Tsutsumino
• Affiliation: Tokyo women's medical university Institute of Rheumatology

Key inclusion & exclusion criteria

Inclusion criteria:
Exclusion criteria: Exclusion Criteria Patients who meet any of these criteria will not be enrolled in this study: Eosinophilic granulomatosis with polyangiitis or anti-glomerular basement membrane antibody disease patients. Other collagen diseases or systemic autoimmune diseases patients. Severity: limited disease according to EUVAS criteria. Those having serious lung, renal or heart disease. Those having infarction or bleeding of gastrointestinal tract or having diverticulitis.. Those having a history of severe drug allergic reactions. Those having an active infection or a deep-seated infection within 6 months of randomization. Those having active hepatitis B or a history of infection with HBV. Those having positive anti-HBs antibody or anti-HBc antibody, and HBV-DNA. Those having active hepatitis C or a history of hepatitis C. Those having an ALT or AST level greater than 2.5 times of the upper limit of normal. Those having active tuberculosis or mycosis Those having CMV antigenemia They have or have a history of malignancy, leukemia, lymphoma or lymphoproliferative disease in the past 5 years. Those having uncontrolled other disease. Those having a white blood cell count less than 4,000/mm3 or a platelet count less than 120,000/mm3. Those who have received TCZ or other biological agents. Those who were intolerant to CYC or AZA. Those who started GC or increased a dosage of GC within 4 weeks prior to enrollment. Those who started GC at or increased a dosage of GC to a prednisone-equivalent dose greater than 25mg per day between 5 and 8weeks prior to enrollment. Those who started or increased a dosage of immunosuppressive agents except for GC within 8 weeks prior to enrollment. Those who were treated with plasma exchange or IVIG within 4 weeks prior to enrollment. Those who received a live vaccine within 4 weeks prior to enrollment. Those who were enrolled in another clinical trial and received an investigational agent within 12 weeks prior to enrollment.

Age minimum: 20years-old
Age maximum: 85years-old
Gender: Male and Female

Health Condition(s) or Problem(s) studied

Microscopic polyangiitis (MPA) Granulomatosis with polyangiitis (GPA)

Intervention(s)

TCZ group Week 0-16: TCZ (8mg/kg) will be administrated intravenously every 2 weeks. Week 20 and 24: TCZ (8mg/kg) will be administrated intravenously every 4 weeks. If a participant does not achieve BVAS v3=0 at week 16, he/she can receive TCZ every 2 weeks until week 24. Week 28-52: If a participant achieves complete remission at week 24, he/she will receive TCZ (8mg/kg) intravenously every 4 weeks until week 48. PSL PSL will be prescribed by the same schedule to both treatment groups. Week 0-24: Oral PSL will be given at a dose of 0.8 mg/kg/day during first 4 weeks. And then, PSL will be tapered according to the prefixed schedule. Week 25-52: Participants continue taking oral PSL at a dose of 7.5mg per day.
IVCY group Week 0-24: CY (15mg/kg, doses will be modified for renal dysfunction) will be administrated intravenously every 4 weeks (at least 3 times, up to 6 times). From 4 weeks after the last IVCY to week 52: If a participants achieves complete remission 4 weeks after the last IVCY, he/she will take azathioprine (AZA) orally every day and continue until week 52. PSL PSL will be prescribed by the same schedule to both treatment groups. Week 0-24: Oral PSL will be given at a dose of 0.8 mg/kg/day during first 4 weeks. And then, PSL will be tapered according to the prefixed schedule. Week 25-52: Participants continue taking oral PSL at a dose of 7.5mg per day.

Primary Outcome(s)

The percentage of participants in complete remission at week 24 after randomization. Complete remission is defined as BVAS v3 = 0 (at week 20 and 24) and daily prednisone at a dose of 7.5mg at week 24.

Secondary Outcome(s)

Percentage of participants maintaining complete remission (BVAS v3 = 0 and daily prednisolone at a dose of 7.5mg) during week 24 to 52 after randomization. Percentage of participants who achieved BVAS v3 = 0 at two consecutive visits during 52 weeks after randomization. Time from randomization to achieving BVAS v3 = 0 at two consecutive visits. Percentage of participants who were able to taper daily prednisolone to a dose of 7.5mg during 52 weeks after randomization. Time from randomization to tapering daily prednisolone to a dose of 7.5mg. Total dosage of prednisolone. Percentage of participants who had flare. Time from randomization to first flare. Changes of BVAS score by categories. VDI SF-36 EQ5D Safety Pharmacokinetics

Secondary ID(s)

JMA-IIA00325

Source(s) of Monetary Support

Japan Medical Association

Secondary Sponsor(s)

Hokkaido university hospital Saitama medical center Tokyo women's medical university hospital Keio university hospital Juntendo university hospital Kyorin university hospital St. Marianna university hospital Okayama university hospital Kagawa university hospital Hospital of the university of occupational and environmental health, Japan Tokyo Medical Center Touhoku University Hospital Kyusyu University Hospital Hiroshima University Hospital

Ethics review

Status: YES
Approval date:
Contact:

[e-mail]

Tokyo women's medical university Hospital

03-5269-7839

[e-mail]