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NCT06481306PHASE1, PHASE2RecruitingAccepts Healthy Volunteers

A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease

Bristol-Myers Squibb

Start Date

7/17/2024

Completion Date

10/28/2029

Summary

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 Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

BMS-986470

DRUG

Placebo

DRUG

Famotidine

DRUG

Pantoprazole

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Conditions

Anemia, Sickle CellHealthy Volunteers

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35233

United States

University of California San Diego - La Jolla

La Jolla, California 92037

United States

UCSF Benioff Children's Hospital Oakland

Oakland, California 94609

United States

Yale-New Haven Hospital

New Haven, Connecticut 06510

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

United States

Local Institution - 0034

Chicago, Illinois 60612

United States

Local Institution - 0001

Lenexa, Kansas 66219

United States

Local Institution - 0064

Baltimore, Maryland 21287

United States

Local Institution - 0024

Boston, Massachusetts 02114

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Local Institution - 0030

St Louis, Missouri 63110

United States

Local Institution - 0033

Greenville, North Carolina 27834

United States

Local Institution - 0028

Cleveland, Ohio 44195

United States

Local Institution - 0029

Philadelphia, Pennsylvania 19104

United States

Thomas Jefferson University - Medicine/GI and Hepatology

Philadelphia, Pennsylvania 19107

United States

Local Institution - 0032

Pittsburgh, Pennsylvania 15213

United States

Local Institution - 0027

Greenville, South Carolina 29605

United States

Inova Schar Cancer Institute

Fairfax, Virginia 22031

United States

Virginia Commonwealth University (VCU) Medical Center

Richmond, Virginia 23298

United States

Local Institution - 0050

Vancouver, British Columbia V621Y6

Canada

Local Institution - 0051

Toronto, Ontario M5G 2C4

Canada

Local Institution - 0061

Créteil, 94000

France

Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone

Marseille, 13385

France

Hôpital Universitaire Necker Enfants Malades

Paris, 75015

France

CHU Strasbourg-Hautepierre

Strasbourg, 67098

France

Local Institution - 0011

Milan, Lombardy 20122

Italy

Local Institution - 0037

Padua, 35128

Italy

Local Institution - 0009

Verona, 37134

Italy

University Hospitals Sussex NHS Foundation Trust

East Sussex, Brighton And Hove BN2 1ES

United Kingdom

Local Institution - 0044

London, Greater London SE19RT

United Kingdom

King's College Hospital

London, London, City of SE5 9RL

United Kingdom

Local Institution - 0005

Leeds, LS9 7TF

United Kingdom

Local Institution - 0047

London, W12 0HS

United Kingdom