Clinical trial NCT06481306: A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Anemia, Sickle Cell
Healthy Volunteers
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2024-07-01
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to Day 154
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to Day 154
measure: Number of participants with AEs meeting protocol-defined Dose Limiting Toxicity (DLT) criteria
timeFrame: Up to Day 154
measure: Number of participants with AEs leading to discontinuation
timeFrame: Up to Day 154
measure: Number of deaths
timeFrame: Up to Day 154
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to Day 28
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to Day 28
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Up to Day 28
measure: Dose proportionality of BMS-986470 for Cmax and AUC
timeFrame: Up to Day 28
measure: Change from baseline in total hemoglobin (Hb)
timeFrame: Up to Day 154
measure: Change from baseline in total Hb fractions: adult Hb (HbA)
timeFrame: Up to Day 28
measure: Change from baseline in total Hb fractions: fetal Hb (HbF)
timeFrame: Up to Day 154
measure: Change from baseline in total Hb fractions: sickle Hb (HbS)
timeFrame: Up to Day 154
measure: Change from baseline in markers of red blood cell (RBC) lysis: total Hb
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: aspartate aminotransferase (AST)
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: lactate dehydrogenase (LDH)
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: total bilirubin
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: indirect bilirubin
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: haptoglobin
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: absolute reticulocyte count
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: reticulocyte percentage of RBCs
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: absolute schistocyte count
timeFrame: Up to Day 154
measure: Change from baseline in markers of RBC lysis: schistocyte percentage of RBCs
timeFrame: Up to Day 154
measure: Number of participants achieving HbF ≥ 10%
timeFrame: Up to Day 154
measure: Number of participants achieving HbF ≥ 20%
timeFrame: Up to Day 154
measure: Number of participants achieving HbF ≥ 30%
timeFrame: Up to Day 154
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: Local Institution - 0021
state: California
city: Oakland
country: United States
facility: Local Institution - 0003
state: California
city: New Haven
country: United States
facility: Local Institution - 0022
state: Connecticut
city: Atlanta
country: United States
facility: Local Institution - 0017
state: Georgia
city: Lenexa
country: United States
facility: ICON
state: Kansas
city: Boston
country: United States
facility: Local Institution - 0024
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0016
state: Massachusetts
city: Philadelphia
country: United States
facility: Local Institution - 0007
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0032
state: Pennsylvania
city: Fairfax
country: United States
facility: Local Institution - 0013
state: Virginia
city: Richmond
country: United States
facility: Local Institution - 0014
state: Virginia
city: Strasbourg
country: France
facility: Local Institution - 0025
state: Alsace
city: Marseille
country: France
facility: Local Institution - 0015
city: Paris
country: France
facility: Local Institution - 0023
city: London
country: United Kingdom
facility: Local Institution - 0006
state: London, City Of
city: Leeds
country: United Kingdom
facility: Local Institution - 0005
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: