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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
Accepted
Inclusion Criteria:
Cohort A:
* 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.
Cohort B:
* 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 1.
* 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.
Exclusion Criteria:
Cohort A:
* 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.
Cohort B:
* 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-986470.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Primary outcome measure(s)
Number of participants with adverse events (AEs) — Up to 26 months
Number of participants with serious adverse events (SAEs) — Up to 26 months
Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria — Up to 26 months
Number of participants with AEs leading to discontinuation — Up to 26 months
Number of deaths — Up to 26 months
Proportion of participants achieving HbF ≥ 10% — Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 20% — Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 30% — Up to 28 days after last dose
Trial sites (32)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
Recruiting
University of California San Diego - La Jolla
La Jolla
California
Recruiting
UCSF Benioff Children's Hospital Oakland
Oakland
California
Recruiting
Yale-New Haven Hospital
New Haven
Connecticut
Recruiting
Winship Cancer Institute of Emory University
Atlanta
Georgia
Recruiting
Local Institution - 0034
Chicago
Illinois
Not Yet Recruiting
Local Institution - 0001
Lenexa
Kansas
Active Not Recruiting
Local Institution - 0064
Baltimore
Maryland
Not Yet Recruiting
Local Institution - 0024
Boston
Massachusetts
Not Yet Recruiting
Boston Medical Center
Boston
Massachusetts
Recruiting
Local Institution - 0030
St Louis
Missouri
Not Yet Recruiting
Local Institution - 0033
Greenville
North Carolina
Not Yet Recruiting
Local Institution - 0028
Cleveland
Ohio
Not Yet Recruiting
Local Institution - 0029
Philadelphia
Pennsylvania
Not Yet Recruiting
Thomas Jefferson University - Medicine/GI and Hepatology
Philadelphia
Pennsylvania
Recruiting
Local Institution - 0032
Pittsburgh
Pennsylvania
Not Yet Recruiting
Local Institution - 0027
Greenville
South Carolina
Not Yet Recruiting
Inova Schar Cancer Institute
Fairfax
Virginia
Recruiting
Virginia Commonwealth University (VCU) Medical Center
Richmond
Virginia
Recruiting
Local Institution - 0050
Vancouver
British Columbia
Not Yet Recruiting
Local Institution - 0061
Créteil
France
Not Yet Recruiting
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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