Anemia, Sickle Cell, Healthy Volunteers
Conditions
Brief 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.
Interventions
DRUGBMS-986470
Specified dose on specified days
DRUGPlacebo
Specified dose on specified days
DRUGFamotidine
Specified dose on specified days
DRUGPantoprazole
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Proportion of participants achieving HbF ≥ 10% | Up to 28 days after last dose |
| Proportion of participants achieving HbF ≥ 20% | Up to 28 days after last dose |
| Proportion of participants achieving HbF ≥ 30% | Up to 28 days after last dose |
| Number of participants with adverse events (AEs) | Up to 26 months |
| Number of participants with serious adverse events (SAEs) | Up to 26 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants achieving HbF ≥ 30% | Up to 26 months | Cohort B |
| Median time to achieve HbF ≥ 30% | Up to 26 months | Cohort B |
| Median duration of HbF at or above 30% | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH) | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: total bilirubin | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: indirect bilirubin | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: haptoglobin | Up to 26 months | Cohort B |
| Maximum observed plasma concentration (Cmax) | Up to Day 28 | Cohort A Parts 1 and 2 and Cohort B Part 1 |
| Area under the concentration-time curve (AUC) | Up to Day 28 | Cohort A Parts 1 and 2 and Cohort B Part 1 |
| Time of maximum observed plasma concentration (Tmax) | Up to Day 28 | Cohort A Parts 1 and 2 and Cohort B Part 1 |
| Dose proportionality of BMS-986470 for Cmax and AUC | 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 |
| Change from baseline in total hemoglobin (Hb) | Up to 26 months | Cohort A Part 2, Cohort B Parts 1 and 2 |
| Change from baseline in total Hb fractions: adult Hb (HbA) | Up to Day 28 | Cohort A Part 2 |
| Change from baseline in total Hb fractions: fetal Hb (HbF) | Up to 26 months | Cohort A Part 2, Cohort B Parts 1 and 2 |
| Change from baseline in total Hb fractions: sickle Hb (HbS) | Up to 26 months | Cohort B |
| Change from baseline in markers of red blood cell (RBC) lysis: total Hb | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: absolute reticulocyte count | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST) | Up to 26 months | Cohort B |
| Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs | Up to 26 months | Cohort B |
| Number of participants achieving HbF ≥ 10% | Up to 26 months | Cohort B |
| Median time to achieve HbF ≥ 10% | Up to 26 months | Cohort B |
| Median duration of HbF at or above 10% | Up to 26 months | Cohort B |
| Number of participants achieving HbF ≥ 20% | Up to 26 months | Cohort B |
| Median time to achieve HbF ≥ 20% | Up to 26 months | Cohort B |
| Median duration of HbF at or above 20% | Up to 26 months | Cohort B |
Countries
Canada, France, Italy, United Kingdom, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed