Clinical trial NCT02115997: A Study Evaluating the Safety and Efficacy of Rituximab in Combination With Glucocorticoids in Participants With Wegener's Granulomatosis or Microscopic Polyangitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Wegener's Granulomatosis or Microscopic Polyangiitis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-04-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
timeFrame: Baseline up to 6 months
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of Participants Who Achieved a BVAS/WG Score of 0 During Treatment With Prednisone at a Dose of Less Than (<) 10 mg/day
timeFrame: 6 months
measure: 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
timeFrame: 6 months
measure: Percentage of Participants Who Achieved and Maintained Partial Remission (Defined as Having a BVAS/WG of 1 or 2)
timeFrame: 6 months
measure: Number of Severe Flares
timeFrame: At Months 2, 4, 6
measure: Number of Limited Flares
timeFrame: At Months 2, 4, 6
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Yashoda Hospital
state: Andhra Pradesh
city: Gurgaon
country: India
facility: Medanta-The Medicity
state: Haryana
city: Gurgaon
country: India
facility: Fortis Memorial Research Instititute
state: Haryana
city: Mysuru
country: India
facility: Apollo BGS Hospitals
state: Karnataka
city: Mumbai
country: India
facility: Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute; Department of Rheumatologz
state: Maharashtra
city: Bangalore
country: India
facility: St. John's Medical College Hospital; Rheumatology
city: Bangalore
country: India
facility: Chanre Rheumatology and Immunology Center and Research
city: Gujarat
country: India
facility: MULJIBHAI PATEL UROLOGICAL HOSPITAL; Nephrology
city: Nagpur
country: India
facility: Jasleen Hospital
city: Noida
country: India
facility: Fortis Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: