UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000024574
Receipt number R000028278
Scientific Title Clinical trial of tocilizumab versus cyclophosphamide for microscopic polyangiitis and granulomatosis with polyangiitis
Date of disclosure of the study information 2017/05/01
Last modified on 2019/05/07 11:38:41

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Basic information

Public title

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

Acronym

AAVTCZ

Scientific Title

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

Scientific Title:Acronym

AAVTCZ

Region

Japan


Condition

Condition

Microscopic polyangiitis (MPA)
Granulomatosis with polyangiitis (GPA)

Classification by specialty

Pneumology Nephrology Neurology
Clinical immunology Ophthalmology Dermatology
Oto-rhino-laryngology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To compare efficacy and safety between the treatment with intravenous tocilizumab (TCZ) plus high dose glucocorticoids (GC) and the treatment with intravenous cyclophosphamide (IVCY) plus high dose GC, in active patients with MPA and GPA.

Basic objectives2

Pharmacokinetics

Basic objectives -Others


Trial characteristics_1

Exploratory

Trial characteristics_2

Others

Developmental phase

Phase II


Assessment

Primary outcomes

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.

Key secondary outcomes

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


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Cluster

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

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.

Interventions/Control_2

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.

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

85 years-old >

Gender

Male and Female

Key inclusion criteria

1 Those with ANCA positive active MPA or GPA according to the diagnostic criteria of Japanese MHLW, or those with ANCA positive pauci-immune glomerulonephritis without non-renal vasculitis. They must have newly diagnosed MPA or GPA, or have a disease flare that fulfills the inclusion criteria.
2 They must be 20 years of age or older and be under 80 years old.
3 They must weigh at least 40 kg.
4 They must have active disease with BVAS v3 more than 3 with one or more of the major BVAS items. Or they must have active disease severe enough to require treatment with CY (i.e., an organ threatening disease if not treated appropriately) according to the discretion of site investigators.
5 Serum C-reactive protein level must be grater than1.0 mg/dl.
6 They must be willing to practice medically acceptable contraception until 70 days after the last administration of TCZ and until 90 days after the last administration of IVCY or AZA.
7 For female participants, they must be willing to refrain from breastfeeding throughout the trial.
8 They must be willing to comply with study procedures, including completion of all visits and treatments
9 They must be willing and able to provide informed consent.

Key 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.

Target sample size

48


Research contact person

Name of lead principal investigator

1st name Masayoshi
Middle name
Last name Harigai

Organization

Tokyo women's medical university

Division name

Institute of Rheumatology

Zip code

1628666

Address

8-1 kawada-cho shinjyuku-ku Tokyo Japan

TEL

03-3353-8111

Email

harigai.masayoshi@twmu.ac.jp


Public contact

Name of contact person

1st name Michi
Middle name
Last name Tsutsumino

Organization

Tokyo women's medical university

Division name

Institute of Rheumatology

Zip code

1628666

Address

8-1 kawada-cho shinjyuku-ku Tokyo Japan

TEL

03-3353-8111

Homepage URL


Email

tsutsumino.michi@twmu.ac.jp


Sponsor or person

Institute

Tokyo women's medical university
Institute of rheumatology

Institute

Department

Personal name



Funding Source

Organization

Japan Medical Association

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization



Other related organizations

Co-sponsor

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

Name of secondary funder(s)



IRB Contact (For public release)

Organization

Tokyo women's medical university Hospital

Address

8-1 kawada-cho shinjyuku-ku Tokyo Japan

Tel

03-5269-7839

Email

ar.twmu-chiken-ar@smo-msr.co.jp


Secondary IDs

Secondary IDs

YES

Study ID_1

JMA-IIA00325

Org. issuing International ID_1

Japan Medical Association

Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

東京女子医科大学病院(東京都)
北海道大学病院(北海道)
埼玉医科大学総合医療センター(埼玉県)
慶應義塾大学病院(東京都)
順天堂大学医学部附属順天堂医院(東京都)
杏林大学医学部付属病院(東京都)
聖マリアンナ医科大学病院(神奈川県)
岡山大学病院(岡山県)
香川大学医学部附属病院(香川県)
産業医科大学病院(福岡県)


Other administrative information

Date of disclosure of the study information

2017 Year 05 Month 01 Day


Related information

URL releasing protocol


Publication of results

Unpublished


Result

URL related to results and publications


Number of participants that the trial has enrolled


Results


Results date posted


Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics


Participant flow


Adverse events


Outcome measures


Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Open public recruiting

Date of protocol fixation

2016 Year 10 Month 30 Day

Date of IRB


Anticipated trial start date

2018 Year 07 Month 02 Day

Last follow-up date


Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information



Management information

Registered date

2016 Year 10 Month 26 Day

Last modified on

2019 Year 05 Month 07 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028278


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name