A Multicenter, Open-label, Phase IIb Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Rilzabrutinib in Patients With Warm Autoimmune Hemolytic Anemia (LUMINA 2)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 22
- 试验地点
- 53
- 主要终点
- Part A: Proportion of participants with overall hemoglobin response
研究概览
简要总结
All participants will receive rilzabrutinib orally. The screening period is up to 28 days, followed by a treatment period of 24 weeks for Part A. Participants who complete Part A and are deemed eligible for Part B can continue in the Core Part B period followed by an Extended Part B period for up to 253 weeks.
There will be a 7-day safety follow-up period after receiving the last dose of study medication either in Part A (for those not eligible for Part B or early terminated) or Part B. In addition, each participant will be asked to attend an EOT-Core Part B visit when the last participant completes 52 weeks in Core Part B. The Extended Part B period will last for up to 253 weeks.
The study is currently in the Part B Extension segment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients with a confirmed diagnosis of primary wAIHA or systemic lupus erythematosus (SLE)-associated wAIHA (without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations)
- •Participants who have previously failed to maintain a sustained response after treatment with corticosteroids.
- •Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.
- •Up-to-date vaccination status as per local guidelines.
- •Body mass index (BMI) >17.5 and <40 kg/m2
- •All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Core Part B
- •Evidence of treatment efficacy to rilzabrutinib as defined by achieving overall response during Part A.
- •Completion of Part A treatment period (24 weeks). Extended Part B
- •Completion of Core Part B period.
排除标准
- •Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his or her participation in the study as determined by the Investigator.
- •Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.
- •Secondary wAIHA from any cause including drugs, lymphoproliferative disorders (low-count monoclonal B-cell lymphocytosis is allowed), infectious or autoimmune disease, or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
- •Myelodysplastic syndrome.
- •Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA.
- •HIV infection.
- •Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 half-lives, whichever is greater, prior to treatment start.
- •Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- •Part B only
- •Participants who receive any therapy during Part A known to be active in wAIHA.
- •Presence of unacceptable side effect(s) or toxicity associated with rilzabrutinib such that there is an unfavorable risk-benefit assessment for continued treatment with rilzabrutinib in the opinion of the Investigator and/or Sponsor.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Rilzabrutinib
Oral rilzabrutinib 400 mg BID
干预措施: rilzabrutinib (Drug)
结局指标
主要结局
Part A: Proportion of participants with overall hemoglobin response
时间窗: By Week 24 in Part A
Response is defined as an increase in hemoglobin (Hb) by ≥2 g/dL from baseline and an absence of transfusion in the last 7 days, without biochemical resolution of hemolysis at the time response is achieved and an absence of rescue medications during the last 4 weeks. Complete Response is defined as hemoglobin ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, lactate dehydrogenase (LDH) , haptoglobin, and reticulocytes), and absence of transfusion in the last 7 days and an absence of rescue medications during the last 4 weeks.
Part B: Proportion of participants who maintain durable response achieved during Part A or achieve a durable response during Part B and have a hemoglobin response
时间窗: By Week 50 in Part B
Durable response (Part B) is defined as Hb level ≥10 g/dL with an increase from baseline (Part A) of ≥2 g/dL on three consecutive scheduled visits during Week 24 to Week 50; with absence of transfusion and no rescue medication during the period of 3 consecutive visits and for at least 7 days (transfusions) and 4 weeks (rescue medication) prior to the first consecutive visit.
次要结局
- Proportion of participants with durable hemoglobin response(By Week 24 in Part A)
- Median time from baseline to first hemoglobin response(From Day 1 to Week 24 in Part A)
- Frequency of rescue therapy (any wAIHA-directed therapy other than predniso[lo]ne or transfusion) received(After Week 1 of treatment to Week 24 in Part A and Week 305 in Part B)
- Change from baseline in FACIT-Fatigue scale score(Until Week 24 in Part A and Week 305 in Part B)
- Incidence of treatment emergent adverse events (TEAEs), serious TEAEs, adverse events of special interest (AESIs)(Until Week 24 in Part A and Week 305 in Part B)