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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03815695
• Other study ID #: 4202-HVS-101
• Status: Completed
• Phase: Phase 1
• Start date: December 11, 2018
• Est. completion date: December 17, 2021

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: December 17, 2021
• Est. primary completion date: December 17, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Healthy Volunteers
• Sickle Cell Disease

Intervention

Drug:
• FT-4202/Placebo
Participants will receive FT-4202/placebo and monitored for side effects while undergoing pharmacokinetics and pharmacodynamic studies

Locations

Country	Name	City	State
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 Maryland, Greenebaum Comprehensive Cancer Center (SCD subjects only)	Baltimore	Maryland
United States	Levine Cancer Institute (SCD subjects only)	Charlotte	North Carolina
United States	University of Illinois at Chicago (SCD subjects only)	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center (SCD subjects only)	Cincinnati	Ohio
United States	Medpace Clinical Pharmacology Unit (Healthy Volunteers only)	Cincinnati	Ohio
United States	University of Cincinnati Medical Center (SCD subjects only)	Cincinnati	Ohio
United States	Duke University Medical Center (SCD subjects only)	Durham	North Carolina
United States	The University of Texas Health Science Center at Houston (SCD subjects only)	Houston	Texas
United States	Woodland International Research Group (SCD subjects only)	Little Rock	Arkansas
United States	Collaborative Neuroscience Research, LLC (SCD subjects only)	Long Beach	California
United States	St. Jude Children's Research Hospital (SCD subjects only)	Memphis	Tennessee
United States	Advanced Pharma CR, LLC (SCD subjects only)	Miami	Florida
United States	Columbia University Medical Center (SCD subjects only)	New York	New York
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	Lynn Institute of Tulsa (SCD subjects only)	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Forma Therapeutics, Inc.	Medpace, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum observed plasma concentration (Cmax)		Up to 3 weeks of testing
Primary	Time to maximum observed plasma concentration (Tmax)		Up to 3 weeks of testing
Primary	Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24)		Up to 3 weeks of testing
Primary	Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last)		Up to 3 weeks of testing
Primary	Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf)		Up to 3 weeks of testing
Primary	Terminal elimination half-life (t1/2)		Up to 3 weeks of testing
Primary	Apparent clearance (CL/F)		Up to 3 weeks of testing
Primary	Apparent volume of distribution (Vd/F)		Up to 3 weeks of testing
Primary	Terminal disposition rate constant (Lz)		Up to 3 weeks of testing
Primary	Renal clearance (ClR)		Up to 3 weeks of testing
Secondary	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
Secondary	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
Secondary	Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers		up to 7 days
Secondary	Change from baseline PR after a single dose of FT-4202 in healthy volunteers		up to 7 days
Secondary	Change from baseline QRS after a single dose of FT-4202 in healthy volunteers		up to 7 days
Secondary	Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers		up to 7 days