A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 115
- 试验地点
- 49
- 主要终点
- Effect on the Incidence of Vaso-occlusive Crises (VOCs)
研究概览
简要总结
A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease
详细描述
A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with sickle cell disease (SCD; homozygous sickle hemoglobin [HbSS], sickle-β0 [HbSβ0] thalassemia, or sickle-β+ [HbSβ+] thalassemia) to evaluate the safety and efficacy of the phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52 weeks.
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)
盲法说明
Double-Blind
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
- •Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)
- •Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.
- •Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in the past 12 months at the time of informed consent signing and at randomization (Day 1).
- •Subjects receiving HU must have received it continuously for at least 6 months prior to signing informed consent, and must have been on a stable dose for at least 3 months prior to signing the informed consent, with no anticipated need for dose adjustments during the study including the screening period, in the opinion of the investigator.
- •Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.
- •Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.
排除标准
- •Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).
- •Subjects participating in a chronic/prophylactic RBC transfusion program (i.e., regularly scheduled RBC transfusions); any transfusions within 21 days of screening or baseline Hb measurements
- •Subjects with HbF >25% at screening.
- •Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase >3x upper limit of normal.
- •Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a BMI >35 kg/m
- •Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or acute event of malaria, or who are known to be positive for human immunodeficiency virus (HIV).
- •Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).
- •Prior exposure to IMR-
- •Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least 28 days prior to randomization (Day 1).
- •A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.
- •Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth factor treatment within 3 months of signing the ICF or anticipated need for such agents during the study.
- •Prior gene therapy.
研究组 & 干预措施
Higher dose IMR-687
Oral administration of once daily IMR-687
干预措施: IMR-687 (Drug)
Lower Dose IMR-687
Oral administration of once daily IMR-687
干预措施: IMR-687 (Drug)
Placebo
Oral administration of once daily Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Effect on the Incidence of Vaso-occlusive Crises (VOCs)
时间窗: Baseline to Week 52
Annualized rate of VOCs. For each subject, the total number of VOCs on treatment were divided by the time on treatment divided by 52 weeks. The median was then summarized.
Proportion of Patients With Adverse Events and Serious Adverse Events
时间窗: Baseline to Week 56
Incidence of Adverse Events Incidence of Serious Adverse Events
次要结局
未报告次要终点