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Healthy VolunteersPhase 1NCT03815695

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

A Phase 1 study of Healthy Volunteers and Sickle Cell Disease, run by Forma Therapeutics, Inc. at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 12 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers, Sickle Cell Disease
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
130 participants
Where
18 sitesUnited States
Study dates
11 Dec 2018to 17 Dec 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

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

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Children's Healthcare of Atlanta (SCD subjects only)

    Atlanta, Georgia, 30342

  • Augusta University Medical Center (SCD subjects only)

    Augusta, Georgia, 30912

  • University of Maryland, Greenebaum Comprehensive Cancer Center (SCD subjects only)

    Baltimore, Maryland, 21201

  • Levine Cancer Institute (SCD subjects only)

    Charlotte, North Carolina, 28204

  • University of Illinois at Chicago (SCD subjects only)

    Chicago, Illinois, 60612

  • University of Cincinnati Medical Center (SCD subjects only)

    Cincinnati, Ohio, 45219

  • Medpace Clinical Pharmacology Unit (Healthy Volunteers only)

    Cincinnati, Ohio, 45227

  • Cincinnati Children's Hospital Medical Center (SCD subjects only)

    Cincinnati, Ohio, 45229

  • Duke University Medical Center (SCD subjects only)

    Durham, North Carolina, 27710

  • The University of Texas Health Science Center at Houston (SCD subjects only)

    Houston, Texas, 77030

  • Woodland International Research Group (SCD subjects only)

    Little Rock, Arkansas, 72211

  • Collaborative Neuroscience Research, LLC (SCD subjects only)

    Long Beach, California, 90806

  • St. Jude Children's Research Hospital (SCD subjects only)

    Memphis, Tennessee, 38105

  • Advanced Pharma CR, LLC (SCD subjects only)

    Miami, Florida, 33147

  • Columbia University Medical Center (SCD subjects only)

    New York, New York, 10032

  • Pacific Research Partners (SCD subjects only)

    Oakland, California, 94607

  • UCSF Benioff Children's Hospital Oakland (SCD subjects only)

    Oakland, California, 94609

  • Lynn Institute of Tulsa (SCD subjects only)

    Tulsa, Oklahoma, 74135

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
FT-4202/Placebo
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FT-4202/PlaceboDrug

    Also called Etavopivat

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

Study groups in NCT03815695
Study groupRoleWhat they receive
Single ascending dose cohorts in healthy subjectsExperimentalHealthy 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.
Receives: Drug: FT-4202/Placebo
Multiple ascending dose cohorts in healthy subjectsExperimentalHealthy 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.
Receives: Drug: FT-4202/Placebo
Food Effect Cohort in healthy subjectsExperimentalHealth 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.
Receives: Drug: FT-4202/Placebo
Single ascending dose cohorts in SCD subjectsExperimentalSickle 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.
Receives: Drug: FT-4202/Placebo
Multiple ascending dose cohorts in SCD subjectsExperimentalSickle 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.
Receives: Drug: FT-4202/Placebo
12-week dosing cohort in SCD subjectsExperimentalSickle 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
Receives: Drug: FT-4202/Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 weeks of monitoring

  2. Maximum observed plasma concentration (Cmax)

    Measured: Up to 3 weeks of testing

  3. Time to maximum observed plasma concentration (Tmax)

    Measured: Up to 3 weeks of testing

  4. Area under the plasma concentration-time curve from time zero until the 24-hour time point (AUC0-24)

    Measured: Up to 3 weeks of testing

  5. Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last)

    Measured: Up to 3 weeks of testing

  6. Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf)

    Measured: Up to 3 weeks of testing

  7. Terminal elimination half-life (t1/2)

    Measured: Up to 3 weeks of testing

  8. Apparent clearance (CL/F)

    Measured: Up to 3 weeks of testing

  9. Apparent volume of distribution (Vd/F)

    Measured: Up to 3 weeks of testing

  10. Terminal disposition rate constant (Lz)

    Measured: Up to 3 weeks of testing

  11. Renal clearance (ClR)

    Measured: Up to 3 weeks of testing

Secondary outcomes (6)

  1. 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.

    Measured: Up to 3 weeks of testing

  2. 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

    Measured: up to 7 days

  3. Change from baseline heart rate after a single dose of FT-4202 in healthy volunteers

    Measured: up to 7 days

  4. Change from baseline PR after a single dose of FT-4202 in healthy volunteers

    Measured: up to 7 days

  5. Change from baseline QRS after a single dose of FT-4202 in healthy volunteers

    Measured: up to 7 days

  6. Change from baseline T-wave morphology after a single dose of FT-4202 in healthy volunteers

    Measured: up to 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2019
  2. Study start11 Dec 2018
  3. Primary completion17 Dec 2021
  4. Study completion17 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Single ascending dose escalation and multiple ascending dose escalation study followed by an evaluation of food effects on absorption
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
130 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03815695
Sponsor's protocol ID
4202-HVS-101
Status last verified
Apr 2024
First submitted
21 Dec 2018
Last updated
10 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Saraf SL, Hagar R, Idowu M, Osunkwo I, Cruz K, Kuypers FA, Brown RC, Geib J, Ribadeneira M, Schroeder P, Wu E, Forsyth S, Kelly PF, Kalfa TA, Telen MJ. Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease. Blood Adv. 2024 Aug 27;8(16):4459-4475. doi: 10.1182/bloodadvances.2023012467.

    PubMed 38640200

  • Forsyth S, Schroeder P, Geib J, Vrishabhendra L, Konstantinidis DG, LaSalvia K, Ribadeneira MD, Wu E, Kelly P, Kalfa TA. Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial. Clin Pharmacol Drug Dev. 2022 May;11(5):654-665. doi: 10.1002/cpdd.1058. Epub 2022 Jan 12.

    PubMed 35019238

Questions about this trial

What is this clinical trial studying?

A Phase 1 study of Healthy Volunteers and Sickle Cell Disease, run by Forma Therapeutics, Inc. at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03815695, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2024.

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