A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease
Purpose
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.
Conditions
- Anemia, Sickle Cell
- Healthy Volunteers
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
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Experimental Cohort A Part 1 |
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Experimental Cohort A Part 2 |
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Experimental Cohort A Part 3 |
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Experimental Cohort B Part 1 |
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Experimental Cohort B Part 2 |
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Recruiting Locations
Birmingham, Alabama 35233
Julie Kanter, Site 0008
205-975-2837
La Jolla, California 92037
Srila Gopal, Site 0021
858-822-6276
Oakland, California 94609
Mark Walters, Site 0003
New Haven, Connecticut 06510
Cecelia Calhoun, Site 0022
000-000-0000
Atlanta, Georgia 30322
Fuad El Rassi, Site 0017
404-778-1350
Boston, Massachusetts 02118
Elizabeth Klings, Site 0016
617-638-8265
Philadelphia, Pennsylvania 19107
Sanaa Rizk, Site 0007
000-000-0000
Fairfax, Virginia 22031
Sheinei Alan, Site 0013
571-472-4724
Richmond, Virginia 23298
Thokozeni Lipato, Site 0014
804-828-8870
More Details
- Status
- Recruiting
- Sponsor
- Bristol-Myers Squibb
Study Contact
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com855-907-3286
Clinical.Trials@bms.com