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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02115997
First received: April 14, 2014
Last updated: November 1, 2016
Last verified: November 2016
  Purpose
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 Intervention Phase
Wegener's Granulomatosis or Microscopic Polyangiitis
Drug: Methylprednisolone
Drug: Prednisone
Drug: Rituximab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to 6 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved and Maintained Partial Remission (Defined as Having a BVAS/WG of 1 or 2) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of Severe Flares [ Time Frame: At Months 2, 4, 6 ] [ Designated as safety issue: No ]
  • Number of Limited Flares [ Time Frame: At Months 2, 4, 6 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: July 2015
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ristova

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02115997

Contacts
Contact: Reference Study ID Number: ML28550 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
India
Recruiting
Mumbai, Maharashtra, India, 400 053
Not yet recruiting
Bangalore, India, 560076
Terminated
New Delhi, India, 110017
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02115997     History of Changes
Other Study ID Numbers: ML28550 
Study First Received: April 14, 2014
Last Updated: November 1, 2016
Health Authority: India: National Drug Controller General of India

Additional relevant MeSH terms:
Granulomatosis with Polyangiitis
Systemic Vasculitis
Microscopic Polyangiitis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Autoimmune Diseases
Immune System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Rituximab
Prednisone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 07, 2016