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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers; Anemia, Sickle Cell
• Intervention / Treatment: Drug: Placebo; Drug: Famotidine; Drug: BMS-986470

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V621Y6
      • Not yet recruiting
      • Local Institution - 0050
      • Contact: Site 0050
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Not yet recruiting
      • Local Institution - 0051
      • Contact: Site 0051
• France
  • Créteil, France, 94000
    • Not yet recruiting
    • Local Institution - 0061
    • Contact: Site 0061
  • Marseille, France, 13385
    • Recruiting
    • Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
    • Contact: Sarah SZEPETOWSKI, Site 0015; Phone Number: 33491386778
  • Paris, France, 75015
    • Recruiting
    • Hopital Universitaire Necker Enfants Malades
    • Contact: Olivier Hermine, Site 0023; Phone Number: +33144495663
  • Alsace
    • Strasbourg, Alsace, France, 67033
      • Recruiting
      • Institut de cancérologie Strasbourg Europe (ICANS)
      • Contact: Shanti AME, Site 0025; Phone Number: 0368767401
• Italy
  • Padua, Italy, 35128
    • Not yet recruiting
    • Local Institution - 0037
    • Contact: Site 0037
  • Verona, Italy, 37134
    • Not yet recruiting
    • Local Institution - 0009
    • Contact: Site 0009
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Not yet recruiting
      • Local Institution - 0011
      • Contact: Site 0011
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Not yet recruiting
    • Local Institution - 0005
    • Contact: Site 0005
  • London, United Kingdom, W12 0HS
    • Not yet recruiting
    • Local Institution - 0047
    • Contact: Site 0047
  • Brighton And Hove
    • East Sussex, Brighton And Hove, United Kingdom, BN2 1ES
      • Recruiting
      • University Hospitals Sussex NHS Foundation Trust
      • Contact: Tom Rider, Site 0004; Phone Number: 01276667758
  • Greater London
    • London, Greater London, United Kingdom, SE19RT
      • Not yet recruiting
      • Local Institution - 0044
      • Contact: Site 0044
  • London, City of
    • London, London, City of, United Kingdom, SE5 9RL
      • Recruiting
      • King's College Hospital
      • Contact: Moji Awogbade, Site 0006
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Julie Kanter, Site 0008; Phone Number: 205-975-2837
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California San Diego - La Jolla
      • Contact: Srila Gopal, Site 0021; Phone Number: 858-822-6276
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
      • Contact: Mark Walters, Site 0003
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale-New Haven Hospital
      • Contact: Cecelia Calhoun, Site 0022; Phone Number: 000-000-0000
  • Florida
    • Tampa, Florida, United States, 33607
      • Not yet recruiting
      • Local Institution - 0035
      • Contact: Site 0035
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
      • Contact: Fuad El Rassi, Site 0017; Phone Number: 404-778-1350
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Local Institution - 0034
      • Contact: Site 0034
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Active, not recruiting
      • Local Institution - 0001
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Not yet recruiting
      • Local Institution - 0064
      • Contact: Site 0064
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston Medical Center
      • Contact: Elizabeth Klings, Site 0016; Phone Number: 617-638-8265
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Local Institution - 0024
      • Contact: Site 0024
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Local Institution - 0030
      • Contact: Site 0030
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Not yet recruiting
      • Local Institution - 0033
      • Contact: Site 0033
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Local Institution - 0028
      • Contact: Site 0028
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University - Medicine/GI and Hepatology
      • Contact: Sanaa Rizk, Site 0007; Phone Number: 000-000-0000
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Local Institution - 0029
      • Contact: Site 0029
    • Pittsburgh, Pennsylvania, United States, 15213
      • Not yet recruiting
      • Local Institution - 0032
      • Contact: Site 0032
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Not yet recruiting
      • Local Institution - 0027
      • Contact: Site 0027
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Inova Schar Cancer Institute
      • Contact: Sheinei Alan, Site 0013; Phone Number: 571-472-4724
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University (VCU) Medical Center
      • Contact: Thokozeni Lipato, Site 0014; Phone Number: 804-828-8870

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

- Cohort A.

i) 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.

ii) Body mass index (BMI) of 18.0 to 32.0 kg/m^2, inclusive. BMI = weight (kg)/ (height [m])^2 as measured at screening.

iii) 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.

i) Participants with a documented diagnosis of Sickle Cell Disease (SCD) with genotype HbSS, HbSβ0-thal, or HbSβ+-thal.

ii) Participants with ≥ 4 vaso-occlusive crises (VOCs) within the previous 12 months or ≥ 2 VOCs within the previous 6 months.

iii) Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

iv) Must have the following laboratory values:.

A. Hemoglobin ≥ 5.5 and ≤ 12 g/dL (males) or ≥ 5.5 and ≤ 10.6 g/dL (females).

B. Absolute neutrophil count ≥ 1500/μL.

C. Platelet count ≥ 100 × 10^3/μL.

D. Absolute reticulocyte count > 100 × 10^3/μL or > 50 × 10^3/μL if taking hydroxyurea.

Exclusion Criteria

- Cohort A.

i) Any significant medical condition or any condition that confounds the ability to interpret data from the study.

ii) 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.

iii) Any major surgery or planned surgery (except GI surgery) within 12 weeks of the first study intervention administration.

- Cohort B.

i) 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.

ii) 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 or any VOC requiring ≥ 24 hours of hospital admission within 30 days prior to the first dose of study intervention.

iii) Participants with any episode of acute chest syndrome within the last 6 months prior to the first dose of study intervention.

iv) Creatinine clearance (CrCl) < 60 mL/min/1.72m2 using Chronic Kidney Disease Epidemiology (CKD-EPI) equation

• Cohort A and B.

  i) 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A Part 1	Drug: Placebo; Specified dose on specified days; Drug: BMS-986470; Specified dose on specified days
Experimental: Cohort A Part 2	Drug: Placebo; Specified dose on specified days; Drug: BMS-986470; Specified dose on specified days
Experimental: Cohort A Part 3	Drug: Famotidine; Specified dose on specified days; Drug: BMS-986470; Specified dose on specified days
Experimental: Cohort B Part 1	Drug: Placebo; Specified dose on specified days; Drug: BMS-986470; Specified dose on specified days
Experimental: Cohort B Part 2	Drug: BMS-986470; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	Cohort A Parts 1 and 2 and Cohort B Part 1	Up to Day 28
Area under the concentration-time curve (AUC)	Cohort A Parts 1 and 2 and Cohort B Part 1	Up to Day 28
Time of maximum observed plasma concentration (Tmax)	Cohort A Parts 1 and 2 and Cohort B Part 1	Up to Day 28
Dose proportionality of BMS-986470 for Cmax and AUC	Assessed by using the slope of a statistical linear relationship between the ln-transformed PK parameters AUC and Cmax and the ln-transformed dose will be fitted by using power model	Up to Day 28
Change from baseline in total Hb fractions: adult Hb (HbA)	Cohort A Part 2	Up to Day 28
Change from baseline in total hemoglobin (Hb)	Cohort A Part 2, Cohort B Parts 1 and 2	Up to 26 months
Change from baseline in total Hb fractions: fetal Hb (HbF)	Cohort A Part 2, Cohort B Parts 1 and 2	Up to 26 months
Change from baseline in total Hb fractions: sickle Hb (HbS)	Cohort B	Up to 26 months
Change from baseline in markers of red blood cell (RBC) lysis: total Hb	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST)	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH)	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: total bilirubin	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: indirect bilirubin	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: haptoglobin	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: absolute reticulocyte count	Cohort B	Up to 26 months
Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs	Cohort B	Up to 26 months
Number of participants achieving HbF ≥ 10%	Cohort B	Up to 26 months
Number of participants achieving HbF ≥ 20%	Cohort B	Up to 26 months
Number of participants achieving HbF ≥ 30%	Cohort B	Up to 26 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Estimated): January 6, 2027
• Study Completion (Estimated): November 16, 2027

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Famotidine
• Other Study ID Numbers: CA230-1019; 2023-510283-12 (Other Identifier: EU CTR); U1111-1301-6753 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No