A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease
NCT Number: NCT06481306
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Anemia, Sickle Cell|Healthy Volunteers
Interventions: DRUG: BMS-986470|DRUG: Placebo
Sponsor: Bristol-Myers Squibb
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 184
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-17
Completion Date: 2027-11-16
Locations: ICON, Lenexa, Kansas, 66219, United States

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.

Primary Outcome Measures: Number of participants with adverse events (AEs), Up to Day 154|Number of participants with serious adverse events (SAEs), Up to Day 154|Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria, Up to Day 154|Number of participants with AEs leading to discontinuation, Up to Day 154|Number of deaths, Up to Day 154
Secondary Outcome Measures: 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 hemoglobin (Hb), Cohort A Part 2, Cohort B Parts 1 and 2, Up to Day 154|Change from baseline in total Hb fractions: adult Hb (HbA), Cohort A Part 2, Up to Day 28|Change from baseline in total Hb fractions: fetal Hb (HbF), Cohort A Part 2, Cohort B Parts 1 and 2, Up to Day 154|Change from baseline in total Hb fractions: sickle Hb (HbS), Cohort B, Up to Day 154|Change from baseline in markers of red blood cell (RBC) lysis: total Hb, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST), Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH), Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: total bilirubin, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: indirect bilirubin, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: haptoglobin, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: absolute reticulocyte count, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: absolute schistocyte count, Cohort B, Up to Day 154|Change from baseline in markers of RBC lysis: schistocyte percentage of RBCs, Cohort B, Up to Day 154|Number of participants achieving HbF ≥ 10%, Cohort B, Up to Day 154|Number of participants achieving HbF ≥ 20%, Cohort B, Up to Day 154|Number of participants achieving HbF ≥ 30%, Cohort B, Up to Day 154