NCT00104299 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2, PHASE3
Status at capture: COMPLETED
Registry last update: 2017-04-21

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease Remission

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outcome · POSTED

Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy

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outcome · POSTED

Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization

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outcome · POSTED

The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

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outcome · POSTED

The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

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outcome · POSTED

Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups

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outcome · POSTED

Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups

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outcome · POSTED

Number of Subjects Experiencing Serious Adverse Events

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 15 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: Rituximab plus cyclophosphamide placebo (rituximab group)
Drug: Methylprednisolone (or other glucocorticoid)
Drug: Prednisone
label
Rituximab
type
EXPERIMENTAL
intervention Names
Drug: Cyclophosphamide plus rituximab placebo (control group)
Drug: Azathioprine
Drug: Methylprednisolone (or other glucocorticoid)
Drug: Prednisone
label
Control Group
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Rituximab
description
375 mg/m\^2 infusions once weekly for 4 week
name
Rituximab plus cyclophosphamide placebo (rituximab group)
other Names
Rituxan
type
DRUG
arm Group Labels
Control Group
description
2 mg/kg/day orally for months 1-3
name
Cyclophosphamide plus rituximab placebo (control group)
other Names
Cytoxan
type
DRUG
arm Group Labels
Control Group
description
2 mg/kg/day orally for months 4-6
name
Azathioprine
other Names
imuran
type
DRUG
arm Group Labels
Control Group
Rituximab
description
1 g/day intravenously for up to 3 days within 14 days prior to receiving rituximab
name
Methylprednisolone (or other glucocorticoid)
other Names
Medrol
type
DRUG
arm Group Labels
Control Group
Rituximab
description
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.
name
Prednisone
other Names
Deltasone, Liquid Pred, Meticorten, Orasone
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 197
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Disease Remission
time Frame
6 months post-randomization

secondary Outcomes

description
The adverse event rate for the following events considered related to vasculitis: Death; Grade 2 or higher leukopenia or thrombocytopenia; Grade 3 or higher infections; Hemorrhagic cystitis (grade 2 or lower needs confirmation by cytoscopy); Malignancy; Venous thromboembolic event (deep venous thrombosis or pulmonary embolism); Hospitalization resulting either from the disease or from a complication due to study treatment; Infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions (including cytokine release allergic reaction); Cerebrovascular accident
measure
Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy
time Frame
Through common close-out (defined as 18 months after the last participant is enrolled in the trial)
description
The 2-sided 95% CI of the percentage of participants who have a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and have successfully completed the glucocorticoid taper by 6 months post-randomization and the 2-sided 95% CI of the difference between two arms for assessing the superiority of rituximab to control \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease
measure
Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization
time Frame
6 months post-randomization
description
Duration of complete remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of Prednisone to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease
measure
The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
time Frame
18 months post-randomization
description
Duration of remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of glucocorticoid by 6 months post-randomization to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing.
measure
The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
time Frame
18 months post-randomization
description
Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease
measure
Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups
time Frame
18 months post-randomization
description
Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and completing taper of glucocorticoid by 6 months post-randomization. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease
measure
Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups
time Frame
18 months post-randomization

Full study description

brief 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.
detailed Description: 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.

Source references

avail Ipds

comment
ImmPort study identifier is SDY91.
id
SDY91
type
Individual Participant Data Set
url
http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY91
comment
ImmPort study identifier is SDY91.
id
SDY91
type
Study summary, -design, -adverse event(s), -summary of participant assessments, -interventions, -medications, -demographics, -lab tests, -mechanistic assays, -files et al.
url
http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY91
comment
TrialShare study ID is ITN021AI.
id
ITN021AI
type
Individual Participant Data Set
url
https://www.itntrialshare.org/project/home/begin.view?
comment
TrialShare study ID is ITN021AI.
id
ITN021AI
type
Study overview, -data and reports, -participant list, -manuscripts and abstracts, -availability of biospecimens.
url
https://www.itntrialshare.org/project/home/begin.view?

references

citation
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pmid
23902488
type
BACKGROUND
citation
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pmid
20647199
type
RESULT
citation
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pmid
23902481
type
RESULT
citation
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citation
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citation
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pmid
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type
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citation
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citation
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pmid
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citation
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pmid
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type
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