NCT06481306招募中1 期
A Phase 1/2a, First-in-human, Randomized, Double-blinded, Placebo-controlled, Dose-finding Study in Healthy Volunteers and Participants With Sickle Cell Disease to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, pH and Food Effect, and Preliminary Efficacy of BMS-986470
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 224
- 试验地点
- 42
- 主要终点
- Proportion of participants achieving HbF ≥ 10%
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, pH and food effect, and preliminary efficacy of BMS-986470 in healthy volunteers and participants with sickle cell disease.
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
- 是
入选标准
- •Healthy male and female (who are not of childbearing potential) participants, as determined by the investigator based on medical history and other determinations. Females not of childbearing potential must have been amenorrhoeic for at least 12 months without an alternative medical cause and have follicle-stimulating hormone (FSH) levels of at least 40 IU/L or have undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive. BMI = weight (kg)/[height (m)]2 as measured at screening.
- •No evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory assessments beyond what is consistent with the target population.
- •Participants with a documented diagnosis of sickle cell disease (SCD) with genotype HbSS, HbSβ0-thal, or HbSβ+-thal.
- •For Cohort B Part 1 only: Participants with ≥ 4 vaso-occlusive crises (VOCs) within the previous 12 months or ≥ 2 VOCs within the previous 6 months. For Cohort B Part 2 only: Participants with ≥ 2 VOCs and ≤ 15 VOCs within the previous 12 months.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Participants must have the following laboratory values:
- •i) Hemoglobin ≥ 5.5 and ≤ 12 g/dL (males) or ≥ 5.5 and ≤ 10.6 g/dL (females). ii) Absolute neutrophil count ≥ 1500/μL. iii) Platelet count ≥ 100 × 10^3/μL. iv) Absolute reticulocyte count > 100 × 10^3/μL or > 50 × 10^3/μL if taking hydroxyurea.
排除标准
- •Any significant medical condition or any condition that confounds the ability to interpret data from the study.
- •Participant has any condition, including the presence of laboratory abnormalities, that places the participant at unacceptable risk if the participant was to participate in the study.
- •Any major surgery or planned surgery (except GI surgery) within 12 weeks of the first study intervention administration.
- •Participants with any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
- •For Cohort B Part 1 only: participants with more than 6 severe VOCs defined as VOCs requiring ≥ 24 hours of hospital admission within 12 months prior to the first dose of study intervention.
- •For Cohort B Part 1 only: participants with any episode of acute chest syndrome within the last 6 months prior to the first dose of study intervention.
- •Creatinine clearance (CrCl) < 60 mL/min/1.72m2 using Chronic Kidney Disease Epidemiology (CKD-EPI) equation.
- •Cohort A and B:
- •Participant is receiving regularly scheduled RBC or platelet transfusions or has received a RBC transfusion within 28 days and a platelet transfusion within 14 days prior to starting treatment with BMS-
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Cohort A Part 3
Experimental
干预措施: Pantoprazole (Drug)
Cohort A Part 3
Experimental
干预措施: Famotidine (Drug)
Cohort B Part 1
Experimental
干预措施: Placebo (Drug)
Cohort A Part 1
Experimental
干预措施: BMS-986470 (Drug)
Cohort A Part 2
Experimental
干预措施: BMS-986470 (Drug)
Cohort A Part 1
Experimental
干预措施: Placebo (Drug)
Cohort A Part 2
Experimental
干预措施: Placebo (Drug)
Cohort A Part 3
Experimental
干预措施: BMS-986470 (Drug)
Cohort B Part 2
Experimental
干预措施: BMS-986470 (Drug)
Cohort B Part 1
Experimental
干预措施: BMS-986470 (Drug)
结局指标
主要结局
Proportion of participants achieving HbF ≥ 10%
时间窗: Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 20%
时间窗: Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 30%
时间窗: Up to 28 days after last dose
Number of participants with adverse events (AEs)
时间窗: Up to 26 months
Number of participants with serious adverse events (SAEs)
时间窗: Up to 26 months
Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria
时间窗: Up to 26 months
Number of participants with AEs leading to discontinuation
时间窗: Up to 26 months
Number of deaths
时间窗: Up to 26 months
次要结局
- Maximum observed plasma concentration (Cmax)(Up to Day 28)
- Area under the concentration-time curve (AUC)(Up to Day 28)
- Time of maximum observed plasma concentration (Tmax)(Up to Day 28)
- Dose proportionality of BMS-986470 for Cmax and AUC(Up to Day 28)
- Change from baseline in total Hb fractions: adult Hb (HbA)(Up to Day 28)
- Median time to achieve HbF ≥ 10%(Up to 26 months)
- Median duration of HbF at or above 10%(Up to 26 months)
- Median time to achieve HbF ≥ 20%(Up to 26 months)
- Median duration of HbF at or above 20%(Up to 26 months)
- Median time to achieve HbF ≥ 30%(Up to 26 months)
- Median duration of HbF at or above 30%(Up to 26 months)
- Number of participants achieving HbF ≥ 30%(Up to 26 months)
- Number of participants achieving HbF ≥ 20%(Up to 26 months)
- Maximum observed plasma concentration (Cmax)(Up to Day 28)
- Area under the concentration-time curve (AUC)(Up to Day 28)
- Time of maximum observed plasma concentration (Tmax)(Up to Day 28)
- Dose proportionality of BMS-986470 for Cmax and AUC(Up to Day 28)
- Change from baseline in total hemoglobin (Hb)(Up to 26 months)
- Change from baseline in total Hb fractions: adult Hb (HbA)(Up to Day 28)
- Change from baseline in total Hb fractions: fetal Hb (HbF)(Up to 26 months)
- Change from baseline in total Hb fractions: sickle Hb (HbS)(Up to 26 months)
- Change from baseline in markers of red blood cell (RBC) lysis: total Hb(Up to 26 months)
- Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST)(Up to 26 months)
- Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH)(Up to 26 months)
- Change from baseline in markers of RBC lysis: total bilirubin(Up to 26 months)
- Change from baseline in markers of RBC lysis: indirect bilirubin(Up to 26 months)
- Change from baseline in markers of RBC lysis: haptoglobin(Up to 26 months)
- Change from baseline in markers of RBC lysis: absolute reticulocyte count(Up to 26 months)
- Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs(Up to 26 months)
- Number of participants achieving HbF ≥ 10%(Up to 26 months)
研究者
研究点 (42)
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