A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 171
- 主要终点
- Change in total haemoglobin
研究概览
简要总结
This study examines how well a new, potential medicine called NDec works and is tolerated in people with sickle cell disease. NDec is a combination of two medicines (decitabine-tetrahydrouridine). Both medicines are new for the treatment of sickle cell disease. Participants who are not taking Hydroxyurea (HU) will get NDec, NDec and placebo, or placebo. Participants who are on HU treatment before joining the study will get NDec, NDec and placebo, or continue on HU. Which treatment participants get is decided by chance. Participants getting NDec and/or Placebo will get capsules to take twice weekly. The study will last for about a year.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age above or equal to 18 years at the time of signing informed consent
- •Confirmed diagnosis of SCD (including HbSS, HbSC, HbSβ0 thalassaemia and HbSβ+ thalassaemia or other Sickle Cell disease variants)
- •2-10 episodes of documented vaso-occlusive crisis (VOCs) within the last 12 months prior to the screening visit
- •Haemoglobin greater than or equal to 5.0 g/dL and below or equal to 10.5 g/dL at visit 1
- •Absolute reticulocyte count above upper limit of the normal (ULN) at visit 1
- •Body weight 40 to 125 kg (inclusive).
排除标准
- •Patient is on chronic transfusion therapy as defined by receiving scheduled (pre-planned) series of blood transfusion (simple or exchange) for prophylactic purposes, or the patient is likely to begin chronic transfusion therapy during the course of the trial, or has received RBC or whole blood transfusion for any reason within 28 days of visit 1
- •Receipt of erythropoietin or other haematopoietic growth factor treatment within 28 days of signing ICF, or planned treatment with these agents during the trial
- •Receipt of voxelotor, crizanlizumab or L-glutamine treatment within 12 weeks of signing the informed consent form, or planned treatment with such agents during the trial
- •Platelet count greater than 800 x 10^9/L at visit 1
- •Absolute neutrophil count below or equal to 1.5 x 10^9/L at visit 1
- •Any condition/concurrent chronic disease involving the stomach or small intestine which may affect drug absorption, as per investigator's judgement
- •Female who is
- •pregnant, breast-feeding or intends to become pregnant within 6 months after the final trial product administration
- •child-bearing potential and not using highly effective methods of contraception and whose male partner is not using effective contraception, at screening and until 6 months after the last dose of trial product
- •Male with female partner of childbearing potential who does not agree to use condom and whose female partner of childbearing potential is not using a highly effective contraceptive measure from trial start to:
- •Six (6) months after the last dose of trial product for patients on NDec/Placebo
- •Six (6) months after the last dose of trial product for patients outside US and CA randomised to HU
- •Twelve (12) months after the last dose of trial product for patients randomised to HU in US and CA
研究组 & 干预措施
HU-non-eligible - NDec plus placebo
HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
干预措施: NDec - oral decitabine-tetrahydrouridine (Drug)
HU-non-eligible - NDec plus placebo
HU-non eligible patients randomised to treatment with NDec on one day and placebo on the other day
干预措施: Placebo (Drug)
HU-active - NDec plus NDec
HU-active patients randomised to treatment with NDec on both days
干预措施: NDec - oral decitabine-tetrahydrouridine (Drug)
HU-non-eligible - NDec plus NDec
HU-non eligible patients randomised to treatment with NDec on both days
干预措施: NDec - oral decitabine-tetrahydrouridine (Drug)
HU-non-eligible - Placebo plus placebo
HU-non eligible patients randomised to treatment with placebo on both days
干预措施: Placebo (Drug)
HU-active - NDec plus placebo
HU-active patients randomised to treatment with NDec on one day and placebo on the other day
干预措施: NDec - oral decitabine-tetrahydrouridine (Drug)
HU-active - NDec plus placebo
HU-active patients randomised to treatment with NDec on one day and placebo on the other day
干预措施: Placebo (Drug)
HU-active - HU
HU-active patients randomised to continue on open-label HU treatment
干预措施: HU - Hydroxyurea (Drug)
结局指标
主要结局
Change in total haemoglobin
时间窗: From baseline (week 0) to week 24
measured in g/dL
次要结局
- Cmax for tetrahydrouridine from pharmacokinetic assessment(At week 24)
- Change in foetal haemoglobin (g/dL)(From baseline (week 0) to week 24)
- Change in foetal haemoglobin as a proportion of total haemoglobin (%HbF)(From baseline (week 0) to week 24)
- Number of vaso-occlusive crises(From baseline (week 0) to week 48)
- Number of acute chest syndrome(From baseline (week 0) to week 48)
- Number of RBC units transfused(From baseline (week 0) to week 48)
- Number of adverse events of grade 3 or higher(From baseline (week 0) to week 52)
- Change in DNA methyltransferase 1 (DNMT1) activity(From baseline (week 0) to week 24)
- Cmax for decitabine from pharmacokinetic assessment(At week 24)
- Change in cytidine deaminase (CDA) activity(From baseline (week 0) to week 24)
- Change in haemolysis measure: lactate dehydrogenase(From baseline (week 0) to week 24)
- Change in F-cell level as a proportion of total red blood cell (RBC) (%F-cells)(From baseline (week 0) to week 24)
- Change in haemolysis measure: absolute reticulocyte count(From baseline (week 0) to week 24)
- Change in haemolysis measure: indirect bilirubin(From baseline (week 0) to week 24)