A SAD/MAD to Assess the Safety, PK/PD of FT-4202 in Healthy Volunteers and Sickle Cell Disease Patients

A Randomized, Placebo-controlled, Double Blind, Single Ascending and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of FT-4202 in Healthy Volunteers and Sickle Cell Disease Patients

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.

SCD Key Inclusion Criteria:

• Must be between 12 and 65 years of age
• Previously diagnosed sickle cell disease (hemoglobin electrophoresis or genotype)
• Must have a minimum body weight of 40 kg (88 lbs) at the Screening Visit
• Must have the ability to understand and sign written informed consent (and assent where applicable), which must be obtained prior to any study-related procedures being completed
• All male and female patients of child bearing potential must agree to use medically accepted contraceptive regimen during study participation and for 90 days after last study drug administration
• Must be willing to abide by all study requirements and restrictions

SCD Key Exclusion Criteria:

• Had more than 6 episodes of vaso-occlusive crisis (VOC) within the past 12 months that required a hospital, emergency room, or clinic visit

• Had a least one episode of acute chest syndrome in the last 6 months

• Received any of the following approved therapies for use in SCD:

  • Hydroxurea (HU): excluded if started HU < 90 days prior to Day 1 of study treatment
  • Adakveo®: excluded if received an infusion within 14 days prior to Day 1 of study treatment
  • Oxbryta®: excluded if received a dose within 7 days prior to start of Day 1 of study treatment

• Received a red blood cell transfusion within 30 days of starting the study drug

• Hemoglobin < 7.0 g/dL or > 10.5 g/dL

• Unable to take and absorb oral medications

HEALTHY VOLUNTEER Inclusion Criteria: [Note: no longer recruiting subjects for this portion of the study]

• Subjects must be between 18 and 60 years of age
• Subjects must have the ability to understand and sign written informed consent, which must be obtained prior to any study-related procedures being completed
• Subjects must be in general good health, based upon the results of medical history, a physical examination, vital signs, laboratory profile, and a 12-lead ECG
• All males and females of child bearing potential must agree to use medically accepted contraceptive regimen during study participation and up to 90 days after
• Subjects must be willing to abide by all study requirements and restrictions

HEALTHY VOLUNTEER Exclusion Criteria: [Note: no longer recruiting subjects for this portion of the study]

• Evidence of clinically significant medical condition or other condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study
• History of clinically significant cardiac diseases including condition disturbances
• Abnormal hematologic, renal and liver function studies
• History of drug or alcohol abuse