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NCT Number: NCT06481306

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

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.

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Local Institution - 0050, Vancouver, British Columbia, Canada

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BMS-986470

Drug

Specified dose on specified days

Placebo

Drug

Specified dose on specified days

Famotidine

Drug

Specified dose on specified days

Pantoprazole

Drug

Specified dose on specified days

Primary outcomes

  1. Number of participants with adverse events (AEs)

    Time frame: Up to 26 months

  2. Number of participants with serious adverse events (SAEs)

    Time frame: Up to 26 months

  3. Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria

    Time frame: Up to 26 months

  4. Number of participants with AEs leading to discontinuation

    Time frame: Up to 26 months

  5. Number of deaths

    Time frame: Up to 26 months

  6. Proportion of participants achieving HbF ≥ 10%

    Time frame: Up to 28 days after last dose

  7. Proportion of participants achieving HbF ≥ 20%

    Time frame: Up to 28 days after last dose

  8. Proportion of participants achieving HbF ≥ 30%

    Time frame: Up to 28 days after last dose

Secondary outcomes

  1. Maximum observed plasma concentration (Cmax)

    Time frame: Up to Day 28

    Cohort A Parts 1 and 2 and Cohort B Part 1

  2. Area under the concentration-time curve (AUC)

    Time frame: Up to Day 28

    Cohort A Parts 1 and 2 and Cohort B Part 1

  3. Time of maximum observed plasma concentration (Tmax)

    Time frame: Up to Day 28

    Cohort A Parts 1 and 2 and Cohort B Part 1

  4. Dose proportionality of BMS-986470 for Cmax and AUC

    Time frame: Up to Day 28

    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

  5. Change from baseline in total hemoglobin (Hb)

    Time frame: Up to 26 months

    Cohort A Part 2, Cohort B Parts 1 and 2

  6. Change from baseline in total Hb fractions: adult Hb (HbA)

    Time frame: Up to Day 28

    Cohort A Part 2

  7. Change from baseline in total Hb fractions: fetal Hb (HbF)

    Time frame: Up to 26 months

    Cohort A Part 2, Cohort B Parts 1 and 2

  8. Change from baseline in total Hb fractions: sickle Hb (HbS)

    Time frame: Up to 26 months

    Cohort B

  9. Change from baseline in markers of red blood cell (RBC) lysis: total Hb

    Time frame: Up to 26 months

    Cohort B

  10. Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST)

    Time frame: Up to 26 months

    Cohort B

  11. Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH)

    Time frame: Up to 26 months

    Cohort B

  12. Change from baseline in markers of RBC lysis: total bilirubin

    Time frame: Up to 26 months

    Cohort B

  13. Change from baseline in markers of RBC lysis: indirect bilirubin

    Time frame: Up to 26 months

    Cohort B

  14. Change from baseline in markers of RBC lysis: haptoglobin

    Time frame: Up to 26 months

    Cohort B

  15. Change from baseline in markers of RBC lysis: absolute reticulocyte count

    Time frame: Up to 26 months

    Cohort B

  16. Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs

    Time frame: Up to 26 months

    Cohort B

  17. Number of participants achieving HbF ≥ 10%

    Time frame: Up to 26 months

    Cohort B

  18. Median time to achieve HbF ≥ 10%

    Time frame: Up to 26 months

    Cohort B

  19. Median duration of HbF at or above 10%

    Time frame: Up to 26 months

    Cohort B

  20. Number of participants achieving HbF ≥ 20%

    Time frame: Up to 26 months

    Cohort B

  21. Median time to achieve HbF ≥ 20%

    Time frame: Up to 26 months

    Cohort B

  22. Median duration of HbF at or above 20%

    Time frame: Up to 26 months

    Cohort B

  23. Number of participants achieving HbF ≥ 30%

    Time frame: Up to 26 months

    Cohort B

  24. Median time to achieve HbF ≥ 30%

    Time frame: Up to 26 months

    Cohort B

  25. Median duration of HbF at or above 30%

    Time frame: Up to 26 months

    Cohort B

Study contacts

Contact information is provided by the study sponsor or research team.

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

[email protected]

855-907-3286

First line of the email MUST contain NCT # and Site #.

CONTACT

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Jul 1, 2024
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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