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Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis (ITN021AI)


Phase 2/Phase 3
15 Years
N/A
Not Enrolling
Both
Vasculitis, Wegener's Granulomatosis, Microscopic Polyangiitis

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Trial Information

Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis (ITN021AI)


Current conventional therapies for ANCA-associated vasculitis (AAV) are associated with high
incidences of treatment failure, disease relapse, substantial toxicity, and patient
morbidity and mortality. Rituximab is a monoclonal antibody used to treat non-Hodgkin's
lymphoma. This study will evaluate the efficacy of rituximab with glucocorticoids in
inducing disease remission in patients with severe forms of AAV (WG and MPA).

The study consists of two phases: a 6-month remission induction phase, followed by a
12-month remission maintenance phase. All participants will receive at least 1 g of pulse
intravenous methylprednisolone or a dose-equivalent of another glucocorticoid preparation.
Depending on the participant's condition, he or she may receive up to 3 days of intravenous
methylprednisolone for a total of 3 g of methylprednisolone (or a dose-equivalent). During
the remission induction phase, all participants will receive oral prednisone daily (1
mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6
study visit.

Next, participants will be randomly assigned to one of two arms. Arm 1 participants will
receive rituximab (375 mg/m^2) infusions once weekly for 4 weeks and cyclophosphamide (CYC)
placebo daily for 3 to 6 months. Arm 2 participants will receive rituximab placebo infusions
once weekly for 4 weeks and CYC daily for 3 to 6 months. During the remission maintenance
phase, participants in Arm 1 will discontinue CYC placebo and start oral azathioprine (AZA)
placebo daily until Month 18. Participants in Arm 2 will discontinue CYC and start AZA daily
until Month 18. Participants who fail treatment before Month 6 will be crossed over to the
other treatment arm unless there are specific contraindications. Participants in either
group who reach clinical remission before they complete 6 months of therapy may switch from
CYC/placebo to AZA/placebo if directed by their physicians.

All participants will be followed for at least 18 months. Initially, study visits are
weekly, progressing to monthly and then quarterly visits as the study proceeds. Blood
collection will occur at each study visit.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Disease Remission

Outcome Description:

A Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) score of 0 with prednisone taper successfully completed at six months. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease.

Outcome Time Frame:

6 months post-randomization

Safety Issue:

No

Principal Investigator

John H. Stone, MD, MPH

Investigator Role:

Study Chair

Investigator Affiliation:

Johns Hopkins University

Authority:

United States: Food and Drug Administration

Study ID:

DAIT ITN021AI

NCT ID:

NCT00104299

Start Date:

January 2005

Completion Date:

January 2010

Related Keywords:

  • Vasculitis
  • Wegener's Granulomatosis
  • Microscopic Polyangiitis
  • ANCA
  • Vasculitis
  • Wegener's Granulomatosis
  • microscopic polyangiitis
  • ANCA-positive
  • ANCA-associated
  • ANCA-associated vasculitis
  • MPA
  • Vasculitis
  • Wegener Granulomatosis
  • Systemic Vasculitis
  • Microscopic Polyangiitis
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
University of AlabamaBirmingham, Alabama  
Boston UniversityBoston, Massachusetts  02118
Duke UniversityDurham, North Carolina  27710
Hospital for Special SurgeryNew York, New York  10021
The Cleveland ClinicCleveland, Ohio  44195
Mayo Clinic FoundationRochester, Minnesota  55905