FT-4202 is an oral small-molecule agonist of pyruvate kinase red blood cell isozyme (PKR) being developed for the treatment of hemolytic anemias. This initial study will characterize the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of a single ascending dose and multiple ascending doses of FT-4202 in the context of Phase 1 studies in healthy volunteers and sickle cell disease patients. The effects of food on the absorption of FT-4202 will also be evaluated in healthy volunteers.
This is a first-in-human (FIH), Phase 1 study of FT-4202 that will characterize the safety, PK and PD of FT-4202 after a single dose and after repeated dosing first in healthy adult volunteers and then in adolescents or adults with sickle cell disease (SCD). Initially, a dose range of FT-4202 in single ascending dose (SAD) escalation cohorts will be explored in healthy subjects. Enrollment of healthy subjects into 2-week multiple ascending dose (MAD) escalation cohorts will be initiated once the safety and PK from at least two SAD cohorts is available to inform the doses for the 2-week MAD portion of the study. The MAD cohorts will then run in parallel to the single dose cohorts. A single dose cohort of healthy subjects is planned to understand food effects (FE) on the PK of FT-4202. After the SAD and FE studies in healthy subjects are completed, the safety, PK, and PD of a single dose of FT-4202 that was found to be safe in healthy subjects will then be evaluated in SCD subjects. Multiple dose studies in SCD subjects will then be initiated upon completion of MAD studies in healthy volunteers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
130
Participants will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Woodland International Research Group (SCD subjects only)
Little Rock, Arkansas, United States
Collaborative Neuroscience Research, LLC (SCD subjects only)
Long Beach, California, United States
Pacific Research Partners (SCD subjects only)
Oakland, California, United States
UCSF Benioff Children's Hospital Oakland (SCD subjects only)
Oakland, California, United States
Advanced Pharma CR, LLC (SCD subjects only)
Miami, Florida, United States
Children's Healthcare of Atlanta (SCD subjects only)
Atlanta, Georgia, United States
Augusta University Medical Center (SCD subjects only)
Augusta, Georgia, United States
University of Illinois at Chicago (SCD subjects only)
Chicago, Illinois, United States
University of Maryland, Greenebaum Comprehensive Cancer Center (SCD subjects only)
Baltimore, Maryland, United States
Columbia University Medical Center (SCD subjects only)
New York, New York, United States
...and 8 more locations
Incidence, frequency, and severity of adverse events (AEs) per CTCAE v5.0 of a single ascending dose and multiple ascending doses of FT-4202 in adult healthy volunteers and SCD patients.
Time frame: Up to 3 weeks of monitoring
Maximum observed plasma concentration (Cmax)
Time frame: Up to 3 weeks of testing
Time to maximum observed plasma concentration (Tmax)
Time frame: Up to 3 weeks of testing
Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24)
Time frame: Up to 3 weeks of testing
Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last)
Time frame: Up to 3 weeks of testing
Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf)
Time frame: Up to 3 weeks of testing
Terminal elimination half-life (t1/2)
Time frame: Up to 3 weeks of testing
Apparent clearance (CL/F)
Time frame: Up to 3 weeks of testing
Apparent volume of distribution (Vd/F)
Time frame: Up to 3 weeks of testing
Terminal disposition rate constant (Lz)
Time frame: Up to 3 weeks of testing
Renal clearance (ClR)
Time frame: Up to 3 weeks of testing
Change from baseline in the levels of 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) in the red blood cells (RBCs) of healthy volunteers and SCD patients after single and multiple doses of FT-4202.
Time frame: Up to 3 weeks of testing
Model-based estimate of change from baseline QT interval corrected using Fridericia's correction formula (QTcF) and 90% confidence interval at the estimated Cmax after a single dose of FT-4202 in healthy volunteers
Time frame: up to 7 days
Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers
Time frame: up to 7 days
Change from baseline PR after a single dose of FT-4202 in healthy volunteers
Time frame: up to 7 days
Change from baseline QRS after a single dose of FT-4202 in healthy volunteers
Time frame: up to 7 days
Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers
Time frame: up to 7 days
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