Healthy Volunteers, Sickle Cell Disease
Conditions
Brief summary
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.
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.
Interventions
DRUGFT-4202/Placebo
Participants will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies
Sponsors
Medpace, Inc.
Forma Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
randomized double blind
Intervention model description
Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Renal clearance (ClR) | Up to 3 weeks of testing |
| Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last) | Up to 3 weeks of testing |
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) | Up to 3 weeks of testing |
| Terminal elimination half-life (t1/2) | Up to 3 weeks of testing |
| Apparent clearance (CL/F) | Up to 3 weeks of testing |
| Apparent volume of distribution (Vd/F) | Up to 3 weeks of testing |
| Terminal disposition rate constant (Lz) | Up to 3 weeks of testing |
| 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. | Up to 3 weeks of monitoring |
| Maximum observed plasma concentration (Cmax) | Up to 3 weeks of testing |
| Time to maximum observed plasma concentration (Tmax) | Up to 3 weeks of testing |
| Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24) | Up to 3 weeks of testing |
Secondary
| Measure | Time frame |
|---|---|
| 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 | up to 7 days |
| Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers | up to 7 days |
| Change from baseline PR after a single dose of FT-4202 in healthy volunteers | up to 7 days |
| Change from baseline QRS after a single dose of FT-4202 in healthy volunteers | up to 7 days |
| Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers | up to 7 days |
| 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. | Up to 3 weeks of testing |
Countries
United States
Outcome results
None listed