Rituximab Therapy for the Induction of Remission and Tolerance in ANCA-Associated Vasculitis (ITN021AI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 197
- 试验地点
- 8
- 主要终点
- Disease Remission
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Control Group
干预措施: Azathioprine (Drug)
Control Group
干预措施: Methylprednisolone (or other glucocorticoid) (Drug)
Rituximab
干预措施: Rituximab plus cyclophosphamide placebo (rituximab group) (Drug)
Rituximab
干预措施: Methylprednisolone (or other glucocorticoid) (Drug)
Rituximab
干预措施: Prednisone (Drug)
Control Group
干预措施: Cyclophosphamide plus rituximab placebo (control group) (Drug)
Control Group
干预措施: Prednisone (Drug)
结局指标
主要结局
Disease Remission
时间窗: 6 months post-randomization
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.
次要结局
- Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy(Through common close-out (defined as 18 months after the last participant is enrolled in the trial))
- Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization(6 months post-randomization)
- The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups(18 months post-randomization)
- The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups(18 months post-randomization)
- Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups(18 months post-randomization)
- Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups(18 months post-randomization)