Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 12 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
randomized double blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Single ascending dose cohorts in healthy subjects
Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of FT-4202 or placebo. The first cohort will receive 200 mg of FT-4202 or placebo. Dose escalation will occur if FT-4202 or placebo is tolerated. The maximum dose of FT-4202 or placebo will be 1500 mg.
  • Drug: FT-4202/Placebo
    Healthy volunteer subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Experimental
Multiple ascending dose cohorts in healthy subjects
Healthy volunteer subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The first cohort will receive 100 mg of FT-4202 or placebo daily X 14 days. The maximum dose of FT-4202/placebo will be 600 mg FT-4202/placebo daily for 14 days.
  • Drug: FT-4202/Placebo
    Healthy volunteer subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Experimental
Food Effect Cohort in healthy subjects
Health Volunteer subject cohort of 10 subjects who will receive a single dose of FT-4202 with food and without food. Dose will be administered per the protocol defined dose.
  • Drug: FT-4202
    Healthy volunteer subjects will receive FT-4202 with or without food and undergo pharmacokinetic studies
Experimental
Single ascending dose cohorts in SCD subjects
Sickle cell disease subject cohort randomized 6:2 receiving a single dose of FT-4202 or placebo. The dose of FT-4202/placebo administered will be a dose that was found to be safe in healthy subjects.
  • Drug: FT-4202/Placebo
    SCD subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Experimental
Multiple ascending dose cohorts in SCD subjects
Sickle cell disease subject cohorts randomized 9:3 to receive FT-4202 or placebo for 14 days continuous dosing. The dose of FT-4202/placebo administered will be a dose less than the maximum tolerable dose evaluated in MAD healthy volunteers.
  • Drug: FT-4202/Placebo
    SCD subjects will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Experimental
12-week dosing cohort in SCD subjects
Sickle cell disease subjects cohort to receive up to 84 consecutive daily doses of open-label FT-4202. The dose of FT-4202 administered will not exceed the highest dose evaluated in the MAD SCD subject cohorts
  • Drug: FT-4202
    SCD subjects will receive FT-4202 and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies

Recruiting Locations

The University of Texas Health Science Center at Houston (SCD subjects only)
Houston, Texas 77030
Contact:
Modupe Idowu, MD
713-500-6764
Modupe.Idowu@uth.tmc.edu

More Details

Status
Recruiting
Sponsor
Forma Therapeutics, Inc.

Study Contact

Forma Therapeutics
617-679-1970
medicalinformation@formatherapeutics.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.