A Phase 1 Open-Label, Multiple-Dose Study to Evaluate Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of FTX-6058 in Subjects With Sickle Cell Disease (SCD) Including an 8-Week Extension Study

About the study

This is a study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of FTX-6058 in subjects with sickle cell disease.

Study point of contact

Call Center
617-651-8853
[email protected]

Locations

6 United States sites

Age

18 Years - 65 Years

Genotypes

Hb as

Phase

Phase 1

Study type

Interventional

Gender

All

Interventions

Drug

participation requirements

Subject is 18 to 65 years of age, inclusive at the time informed consent is obtained.
Subject has signed and dated informed consent form (ICF) before any study-specific procedures are performed and is willing and able to comply with the study procedures and restrictions.
Subjects, who if female and of childbearing potential, agree to use 2 highly effective methods of contraception or practicing abstinence starting at the time of the ICF signing to 90 days after the last dose of study drug, and, who if male, agree to use 2 methods of contraception or practice abstinence from the time of ICF signing to 90 days after the last dose of study drug.
Body mass index between 18 and 32 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.
Documented SCD at the time of screening (S/S, S/β0 and S/β+ genotypes only) as confirmed through review of medical record or HPLC.
If on hydroxyurea (HU) at time of first dose of study drug, a stable dose for a minimum of 3 months is required. If not on HU at time of first dose of study drug, the subject must have been off HU for a minimum of 60 days.
Documented HbF ≤ 20% of total Hb as confirmed through review of medical records or HPLC). If from medical record review, the value must be within the past 12 months.

SCD characterized by both of the following:

Total hemoglobin ≥ 5.5 g/dL and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening
0-6 Vaso-Occlusive Crisis (VOC) episodes over the 12 months prior to screening. A VOC is defined as any event that requires an acute care visit for intravenous (IV) fluid or IV opioid administration.

Subject must meet both of the following laboratory values prior to Week 1 Day 1:

Absolute neutrophil count ≥ 1.5 × 109/L
Platelets ≥ 80 × 109/L
Absolute reticulocyte count at screening higher than 100 × 109/L.

participation restrictions

Major surgery, hospitalization, infection, fever, significant bleeding, cerebrovascular accident or seizure, or transfusion within 14 days prior to study enrollment through conclusion of study follow-up period; elective surgery planned for the time period of the trial.
Sickle cell complication requiring hospitalization in the past 14 days or > 6 total VOCs over the past 12 months requiring hospitalization for ≥ 24 hours.
Use of voxelotor within 60 days prior to starting study drug.
Use of anticoagulants, L-glutamine, crizanlizumab, or medications that induce or inhibit cytochrome P450 (CYP) 3A4, inhibit P-glycoprotein, breast cancer resistance protein, or multidrug and toxin extrusion protein 2-K, or are substrates of CYP2B6 within 14 days prior to first dose of study drug or anticipated need for any of these medications during the study. (Refer to Protocol Section 7.2 and Appendix 3).
Participation in any other investigative treatment studies other than with FTX-6058 within the past 60 days.
History of bone marrow transplant or human stem cell transplant or gene therapies.
Vaccination (including against COVID-19) in the previous 30 days.
Alanine aminotransferase ≥ 3× the upper limit of normal (ULN), albumin < 2.0 mg/dL, direct (conjugated) bilirubin ≥ 1.5 mg/dL, or prothrombin time > 1.5 ULN.
Subjects with a history of severe renal disease defined as estimated glomerular filtration rate < 30 mL/min/1.73m2. Subjects on dialysis of any kind are excluded. Subjects with abnormal laboratory results or medical history indicative of any significant medical disease that, in the opinion of the Investigator, would preclude the subject's participation in the study or potentially obscure the interpretation of the scheduled assessments. Screening laboratory assessments may be repeated up to twice at the discretion of the Investigator. Subjects being treated with antiretroviral agents (such as didanosine and stavudine) because of a higher risk for potentially fatal pancreatitis, hepatic failure, hepatitis, and severe peripheral neuropathy when co-administered with HU. Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C such that subjects are currently on therapy or will be placed on therapy during the trial. Subjects receiving regularly scheduled transfusions to reduce levels of sickle hemoglobin, or any subject who has been transfused in the last 60 days. Clinically diagnosed substance use disorder for alcohol or other illicit drugs of abuse. A positive urine drug screen for illicit drugs of abuse (other than opioids and marijuana/ tetrahydrocannabinol [THC]/ cannabidiol [CBD]) is exclusionary. Pregnant or lactating female; or female of childbearing age unable or unwilling to comply with birth control or abstinence during the study. (Refer to Protocol Section 7.3). Febrile illness in the 7 days prior to baseline visit. Subject is investigative site personnel or member of their immediate family (spouse, parent, child or sibling whether biological or legally adopted). Heart rate corrected QT interval-Frederica's method (QTcF) > 450 msec male or > 470 msec female.

Locations

  • Hollywood, Florida, United States, Foundation for Sickle Cell Disease Research, LLC
  • Atlanta, Georgia, United States, Emory University School of Medicine
  • Atlanta, Georgia, United States, Visionaries Clinical Research
  • Atlanta, Georgia, United States, Atlanta Center for Medical Research
  • Baltimore, Maryland, United States, Axon Clinical Research Institute
  • Bronx, New York, United States, Jacobi Medical Center
Last updated 2022-09-23