A Phase 2b, Double-blind, Randomised, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of VIT-2763 Multiple Doses in Adults With Transfusion-dependent Beta-thalassaemia
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 7
- 主要终点
- Proportion of patients achieving ≥33% reduction of RBC transfusions from baseline and a reduction of ≥2 units assessed consecutively from Week 13 to Week 24 compared to the baseline transfusion
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763 as measured by the reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24, to identify the most efficacious and safe dose.
详细描述
All patients giving written informed consent will undergo a 12-week screening period to determine eligibility for study entry. At Day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner to 1 of 4 treatment groups: VIT-2763 60 mg (once daily), 60 mg (twice daily), or 120 mg (twice daily) or placebo.
The randomisation will be stratified (balanced allocation across treatment groups) according to β0/β0 genotype (yes/no).
The duration of the treatment with VIT-2763 or placebo is 24 weeks, after which patients will undergo a 12-week post-treatment follow-up period.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight ≥40.0 kg and ≤100 kg at screening
- •Documented diagnosis of beta-thalassemia or Hb E/beta-thalassemia
- •Red blood cell (RBC) transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomization and no transfusion-free period for ≥35 days during that period
- •Ability to understand the requirements of the study and provide written informed consent
排除标准
- •Documented diagnosis of Hb S/beta-thalassemia, alpha-thalassemia, or delta beta (δβ)-thalassemia, or hereditary persistence of foetal Hb.
- •History of partial or total splenectomy within 4 months prior to screening.
- •History of myocardial iron overload
- •Chronic liver disease or history of liver cirrhosis
- •Clinically relevant renal disease
- •History or clinically important finding of cardiac disorders
- •History of clinically significant lung disease
- •Uncontrolled hypertension (> Grade 1 according to NCI CTCAE current version)
- •Unable to take and absorb oral medications.
- •Pregnancy or breastfeeding
- •History of drug or alcohol abuse within 2 years prior to screening
- •History or concomitant solid tumors and/or hematological malignancies unless resolved in the ≥5 past years.
研究组 & 干预措施
VIT-2763 60 mg QD
VIT-2763 60 mg administered once daily
干预措施: VIT-2763 60 mg QD (Drug)
VIT-2763 60 mg BID
VIT-2763 60 mg administered twice daily
干预措施: VIT-2763 60 mg BID (Drug)
VIT-2763 120 mg BID
VIT-2763 120 mg administered twice daily
干预措施: VIT-2763 120 mg BID (Drug)
Placebo
Placebo capsule administered twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of patients achieving ≥33% reduction of RBC transfusions from baseline and a reduction of ≥2 units assessed consecutively from Week 13 to Week 24 compared to the baseline transfusion
时间窗: Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1)
次要结局
- Proportion of patients achieving ≥33% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24.(Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1))
- Change from baseline in RBC transfusions over Weeks 13 to 24 compared to the baseline RBC transfusion burden derived using the last 12 weeks prior to randomization.(Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1))
- Proportion of patients achieving ≥50% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24.(Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1))
- Mean change from baseline in Quality of Life (QoL) total score(Week 15 and Week 24 comparing to Baseline (Day 1))