A Study Evaluating the Safety and Efficacy of Rituximab in Combination With Glucocorticoids in Participants With Wegener's Granulomatosis or Microscopic Polyangitis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT02115997

Collaborator

(none)

Enrollment

Locations

Arm

83.1

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a perspective, Phase IV, multi-center, single arm, open-label, interventional study in adult participants with Wegener's granulomatosis (granulomatosis with polyangiitis [GPA]) or microscopic polyangiitis. Participants will be treated with rituximab (Ristova) and glucocorticoids. Rituximab will be administered by intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) body surface area once weekly during Weeks 1 to 4. Participants will also receive one or three pulses of methylprednisolone (1000 milligram [mg] each), followed by a tapering dose of oral prednisolone (start dose of 1 mg per kilogram per day). The dose of oral prednisone will be reduced as per evaluation by the investigator till the participant is completely off the drug. The participants will be followed up for duration of 6 months from the date of starting rituximab therapy with three follow-up visits at Days 52, 112 and 172. All adverse events occurring during this period will be captured.

Condition or Disease	Intervention/Treatment	Phase
Wegener's Granulomatosis or Microscopic Polyangiitis	Drug: Methylprednisolone Drug: Prednisone Drug: Rituximab	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Actual Study Start Date :

Jul 6, 2015

Actual Primary Completion Date :

Jun 7, 2022

Actual Study Completion Date :

Jun 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rituximab Participants will receive IV infusion of rituximab once weekly from Week 1 to 4. Participants will also receive one pulse of methylprednisolone, followed by a tapering dose of oral prednisolone at the discretion of the investigator. Methylprednisolone may be repeated up to total of 3 pulses at the discretion of the investigator.	Drug: Methylprednisolone Methyprednisolone will be administered 1 to 3 pulses at a dose of 1000 milligram (mg) IV at the discretion of the investigator. Drug: Prednisone Prednisone will be administered orally at tapered dose (start at 1 milligrams per kilogram per day [mg/kg/day]) at the discretion of investigator given daily until participants are off the drug. Drug: Rituximab Rituximab will be administered at 375 milligrams per meter square (mg/m^2) of body surface area given by IV infusion once weekly from Week 1 to 4. Other Names: Ristova

Arm

Intervention/Treatment

Experimental: Rituximab

Participants will receive IV infusion of rituximab once weekly from Week 1 to 4. Participants will also receive one pulse of methylprednisolone, followed by a tapering dose of oral prednisolone at the discretion of the investigator. Methylprednisolone may be repeated up to total of 3 pulses at the discretion of the investigator.

Drug: Methylprednisolone

Methyprednisolone will be administered 1 to 3 pulses at a dose of 1000 milligram (mg) IV at the discretion of the investigator.

Drug: Prednisone

Prednisone will be administered orally at tapered dose (start at 1 milligrams per kilogram per day [mg/kg/day]) at the discretion of investigator given daily until participants are off the drug.

Drug: Rituximab

Rituximab will be administered at 375 milligrams per meter square (mg/m^2) of body surface area given by IV infusion once weekly from Week 1 to 4.

Other Names:

Ristova

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Adverse Events and Serious Adverse Events [Baseline up to 6 months]
Percentage of Participants Who Achieved a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) Score of 0 and Successfully Completed Prednisone Taper at 6 Months [6 months]

Secondary Outcome Measures

Percentage of Participants Who Achieved a BVAS/WG Score of 0 During Treatment With Prednisone at a Dose of Less Than (<) 10 mg/day [6 months]
Percentage of Participants With Refractory Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis (AAV) Who Achieved BVAS/WG Score of 0 and Successfully Completed Prednisone Taper at 6 Months [6 months]
Percentage of Participants Who Achieved and Maintained Partial Remission (Defined as Having a BVAS/WG of 1 or 2) [6 months]
Number of Severe Flares [At Months 2, 4, 6]
Number of Limited Flares [At Months 2, 4, 6]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or non-pregnant, non-nursing female
Diagnosed with Wegener's granulomatosis or Microscopic polyangiitis according to the definitions of the Chapel Hill Consensus Conference
Participants with either newly diagnosed or relapsing disease
Participants must have active disease as per the BVAS/WG greater than equal to (>/=) 3 that would normally require treatment with cyclophosphamide (CYC)
Participants willing to practice medically acceptable contraception during and 1 year after the completion of rituximab therapy
Participants must have severe disease i.e. one or more of the major BVAS/WG items depicting severity or disease severe enough to require treatment with CYC.
Participants must be positive for either proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCA) or myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) at the screening

Exclusion Criteria:

History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
Participants in a severely immunocompromised state
Participants with severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
Participants having active severe infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections
Participants who had a live vaccine fewer than 4 weeks before first dose of rituximab
Any other condition which puts the participant to undue risk for rituximab therapy as per local prescribing information or Investigator's judgment
Participants with any previous treatment with rituximab
Participants with any previous treatment with alemtuzumab
Participants who have had treatment with infliximab within the previous 3 months
Participants who have had treatment with adalimumab within the previous 2 months
Participants who have had treatment with etanercept within the previous month
Participants with any other investigational medication within the previous month

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yashoda Hospital	Hyderabad	Andhra Pradesh	India	500082
2	Medanta-The Medicity	Gurgaon	Haryana	India	122001
3	Fortis Memorial Research Instititute	Gurgaon	Haryana	India	122002
4	Apollo BGS Hospitals	Mysuru	Karnataka	India	570023
5	Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute; Department of Rheumatologz	Mumbai	Maharashtra	India	400053
6	St. John's Medical College Hospital; Rheumatology	Bangalore		India	560034
7	Chanre Rheumatology and Immunology Center and Research	Bangalore		India	560079
8	MULJIBHAI PATEL UROLOGICAL HOSPITAL; Nephrology	Gujarat		India	387001
9	Jasleen Hospital	Nagpur		India	440010
10	Fortis Hospital	Noida		India	201 301