A Phase 2a, Double-blind, Randomised, Placebo-controlled, Efficacy, and Safety Study of Multiple Doses of VIT-2763 in Subjects With Sickle Cell Disease (ViSionSerenity)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 22
- 主要终点
- Mean Change From Baseline in Haemolysis Marker (Indirect Bilirubin)
研究概览
简要总结
The purpose of this study is to investigate the effect of VIT-2763 on markers of hemolysis (breakdown in red blood cells) in sickle cell disease (SCD). The safety, tolerability and clinical beneficial effects of VIT-2763 for the treatment of SCD are also explored.
详细描述
At randomization/baseline, participants are randomized into 3 VIT-2763 dose groups to receive either 60 mg twice daily (BID) (Cohort 1), or 120 mg BID (Cohort 2), or 120 mg 3 times daily (TID) (Cohort 3) and 2 placebo groups (BID, Cohort 4a or TID, Cohort 4b).
The expected duration of patient participation is a maximum of 16 weeks, including a non-treatment screening period of up to 4 weeks, and 8-week treatment period, and a 4-week safety 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects with confirmed diagnosis of SCD, including only HbS/S or HbS/βT0 genotype.
- •Subjects who had at least 1 and no more than 10 vaso-occlusive crises (VOC) episodes reported within 12 months prior to screening.
- •Body weight ≥40 kg and ≤120 kg at screening and baseline.
- •Subjects on concomitant hydroxyurea must be on a stable dose (mg/kg) for ≥3 months prior to screening Visit V1
- •Female subjects of childbearing potential, must have negative pregnancy, must have stopped breastfeeding as of first dose, and must either commit to true abstinence from heterosexual contact or must be willing to use adequate contraceptive precautions.
- •Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential
排除标准
- •Hb level <6.0 g/dl or >10.4 g/dl for female participants and >11.0 g/dl for male participants, at screening Visit V1
- •Having received red blood cell (RBC) transfusion therapy within 4 weeks prior to screening, or ongoing or planned RBC transfusion therapy during the course of the study
- •Low levels of Ferritin or transferrin saturation or total iron-binding capacity at screening
- •Subjects being hospitalized for SCD-related events within 14 days before the screening visit
- •Chronic liver disease or history of liver cirrhosis, and/or high levels of alanine aminotransferase or aspartate aminotransferase at baseline
- •Low estimated glomerular filtration rate, and/or significant high urinary albumin/creatinine ratio at screening or on chronic dialysis.
- •Newly diagnosed folate deficiency anemia, which is considered clinically relevant by the Investigator at screening
- •Any history or clinically important finding of cardiac or pulmonary disorders
- •Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death
- •Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy. Note: A subject meeting this criterion should delay screening and/or enrolment for a minimum of 2 weeks, or if excluded can be re-screened at a later time point.
- •Concomitant use of certain hormonal contraceptives as defined in the study protocol, are not allowed within 4 weeks prior to screening and until 1 week after the last administration of the study drug and the use of progesterone-only hormonal contraception as the sole measure to prevent pregnancy.
- •Pregnant or females currently breastfeeding.
- •History or known concomitant solid tumours and/or haematological malignancies unless resolved in the ≥2 past years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, incidental histologic finding of prostate cancer
- •Unable to take and absorb oral medications
- •Acute peptic stomach or duodenal ulcer in the previous 6 months before screening and/or healed after 3 months of treatment.
- •Uncontrolled hemorrhages
研究组 & 干预措施
Cohort 1
Participants receive VIT-2763 60 mg, twice a day during 8 weeks.
干预措施: VIT-2763 120 mg (Drug)
Cohort 2
Participants receive VIT-2763 120 mg, twice a day during 8 weeks.
干预措施: VIT-2763 240 mg (Drug)
Cohort 3
Participants receive VIT-2763 120 mg, three times a day during 8 weeks.
干预措施: VIT-2763 360 mg (Drug)
Cohort 4a
Participants receive a placebo, twice a day during 8 weeks.
干预措施: Placebo BID (Drug)
Cohort 4b
Participants receive a placebo, three times a day during 8 weeks.
干预措施: Placebo TID (Drug)
结局指标
主要结局
Mean Change From Baseline in Haemolysis Marker (Indirect Bilirubin)
时间窗: Baseline and after 8 weeks of treatment
Mean change from baseline in haemolysis markers was measured by reduction of indirect bilirubin.
次要结局
- Mean Change From Baseline in Haemolysis Marker (Direct and Total Bilirubin)(Baseline and after 8 weeks of treatment)
- Mean Change From Baseline in Haemolysis Marker (Lactate Dehydrogenase)(Baseline and after 8 weeks of treatment)
- Mean Change From Baseline in Haemolysis Marker (Potassium)(Baseline and after 8 weeks of treatment)
- Mean Change From Baseline in Haemolysis Marker (Hemoglobin and Haptoglobin)(Baseline and after 8 weeks of treatment)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), TEAEs Related to IMP and by Severity of TEAEs(From first dose of study drug up to 12 weeks)