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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
224
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
Number of participants with adverse events (AEs)
Time frame: Up to 26 months
Number of participants with serious adverse events (SAEs)
Time frame: Up to 26 months
Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria
Time frame: Up to 26 months
Number of participants with AEs leading to discontinuation
Time frame: Up to 26 months
Number of deaths
Time frame: Up to 26 months
Proportion of participants achieving HbF ≥ 10%
Time frame: Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 20%
Time frame: Up to 28 days after last dose
Proportion of participants achieving HbF ≥ 30%
Time frame: Up to 28 days after last dose
Maximum observed plasma concentration (Cmax)
Cohort A Parts 1 and 2 and Cohort B Part 1
Time frame: Up to Day 28
Area under the concentration-time curve (AUC)
Cohort A Parts 1 and 2 and Cohort B Part 1
Time frame: Up to Day 28
Time of maximum observed plasma concentration (Tmax)
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CONTACT
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Specified dose on specified days
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGUniversity of California San Diego - La Jolla
La Jolla, California, United States
RECRUITINGUCSF Benioff Children's Hospital Oakland
Oakland, California, United States
RECRUITINGYale-New Haven Hospital
New Haven, Connecticut, United States
RECRUITINGWinship Cancer Institute of Emory University
Atlanta, Georgia, United States
RECRUITINGLocal Institution - 0034
Chicago, Illinois, United States
NOT_YET_RECRUITINGLocal Institution - 0001
Lenexa, Kansas, United States
ACTIVE_NOT_RECRUITINGLocal Institution - 0064
Baltimore, Maryland, United States
NOT_YET_RECRUITINGLocal Institution - 0024
Boston, Massachusetts, United States
NOT_YET_RECRUITINGBoston Medical Center
Boston, Massachusetts, United States
RECRUITING...and 22 more locations
Cohort A Parts 1 and 2 and Cohort B Part 1
Time frame: 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
Time frame: Up to Day 28
Change from baseline in total hemoglobin (Hb)
Cohort A Part 2, Cohort B Parts 1 and 2
Time frame: Up to 26 months
Change from baseline in total Hb fractions: adult Hb (HbA)
Cohort A Part 2
Time frame: Up to Day 28
Change from baseline in total Hb fractions: fetal Hb (HbF)
Cohort A Part 2, Cohort B Parts 1 and 2
Time frame: Up to 26 months
Change from baseline in total Hb fractions: sickle Hb (HbS)
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of red blood cell (RBC) lysis: total Hb
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST)
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH)
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: total bilirubin
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: indirect bilirubin
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: haptoglobin
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: absolute reticulocyte count
Cohort B
Time frame: Up to 26 months
Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs
Cohort B
Time frame: Up to 26 months
Number of participants achieving HbF ≥ 10%
Cohort B
Time frame: Up to 26 months
Median time to achieve HbF ≥ 10%
Cohort B
Time frame: Up to 26 months
Median duration of HbF at or above 10%
Cohort B
Time frame: Up to 26 months
Number of participants achieving HbF ≥ 20%
Cohort B
Time frame: Up to 26 months
Median time to achieve HbF ≥ 20%
Cohort B
Time frame: Up to 26 months
Median duration of HbF at or above 20%
Cohort B
Time frame: Up to 26 months
Number of participants achieving HbF ≥ 30%
Cohort B
Time frame: Up to 26 months
Median time to achieve HbF ≥ 30%
Cohort B
Time frame: Up to 26 months
Median duration of HbF at or above 30%
Cohort B
Time frame: Up to 26 months