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Phase 3 N=197 Randomized Double-blind Treatment

Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis

Vasculitis · Wegener's Granulomatosis · Microscopic Polyangiitis

Enrolled (actual)
197
Serious AEs
54.3%
Results posted
Aug 2011
Primary outcome: Primary: Disease Remission — 63; 52 Participants — p=<0.001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Rituximab plus cyclophosphamide placebo (rituximab group) (Drug); Cyclophosphamide plus rituximab placebo (control group) (Drug); Azathioprine (Drug); Methylprednisolone (or other glucocorticoid) (Drug); Prednisone (Drug)
Age
Pediatric, Adult, Older Adult · 15+ yrs
Sex
All
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion
Dec 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
Disease Remission
63; 52 <0.001 sig
SECONDARY
Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy
2; 2; 7; 23; 4; 1 0.927
SECONDARY
Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization
62; 51 0.133
SECONDARY
The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
243; 230; NA; NA; NA; NA 0.761
SECONDARY
The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
246; 168; NA; NA; NA; NA 0.861
SECONDARY
Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups
30; 29; 57; 43; 119; 112 0.497
SECONDARY
Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups
176; 177; 180; 183; 189; 266 0.147

Summary

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common type of small blood vessel inflammation in adults. ANCA-associated vasculitis includes Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Rituximab is a man-made antibody used to treat certain types of cancer. The purpose of this study is to determine the effectiveness of rituximab in treating patients with WG and MPA. Study hypothesis: Rituximab is not inferior to conventional therapy in its ability to induce disease remission by Month 6.

Eligibility Criteria

Inclusion Criteria

  • Weight of at least 88 pounds(40 kilograms)
  • Diagnosis of Wegener's granulomatosis or microscopic polyangiitis according to the definitions of the Chapel Hill Consensus Conference
  • Newly diagnosed patient of Wegener's granulomatosis or microscopic polyangiitis OR must be experiencing a disease flare characterized by: (a) active disease with a Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG) of 3 or greater that would normally require treatment with CYC; OR (b) disease severe enough to require treatment with CYC; OR (c) must be positive for either PR3-ANCA (ANCA directed against proteinase 3) or MPO-ANCA (ANCA directed against myeloperoxidase)at the screening
  • Willing to use acceptable forms of contraception for the duration of the study and for up to 1 year after stopping study medications
  • Willing to report pregnancies (female participants or male participants' partners) occurring at any time during the study and for up to 1 year after stopping study medications
  • Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria

  • Diagnosis of Churg-Strauss Syndrome according to the definitions of the Chapel Hill Consensus Conference
  • Have limited disease that would not normally be treated with CYC
  • Requires mechanical ventilation because of alveolar hemorrhage
  • History of severe allergic reactions to human or chimeric monoclonal antibodies
  • Active systemic infection
  • Have a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by pleural cavity or lung abscess, within 6 months prior to study entry
  • History of or current hepatitis B or C infection
  • HIV (human immunodeficiency virus) infected
  • Acute or chronic liver disease that, in the opinion of the investigator, may interfere with the study
  • History of or active cancer diagnosed within the last 5 years. Individuals with squamous cell or basal cell carcinomas of the skin and individuals with cervical carcinoma in situ who have received curative surgical treatment may be eligible for this study.
  • History of anti-glomerular basement membrane (anti-GBM) disease
  • Other uncontrolled disease, including drug and alcohol abuse, that may interfere with the study
  • Pregnancy or breastfeeding
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00104299). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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