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)

This is a Phase 1 multicenter, open-label study evaluating the safety, tolerability, pharmacokinetics (PK), fetal hemoglobin (HbF) induction and biological activity of FTX-6058 in participants 18-65 years of age, inclusive, with SCD.

For more information, visit: https://clinicaltrials.gov/study/NCT05169580

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

Participant is 18 to 65 years of age, inclusive at the time informed consent is obtained.
Participants who meet at least one the following criteria:

• ≥4 episodes of SCD pain crisis over 12 months, or ≥2 over 6 months prior to screening
• ≥2 episodes of SCD pain crisis plus at least one of the following over previous 12 months:
  • Acute chest syndrome (ACS)
  •  Hepatic or splenic sequestration
  • Priapism
• ≥2 of the following events over the previous 12 months:
  •  ACS 
  • Hepatic or splenic sequestration
  •  Priapism 
• SCD-related pulmonary arterial hypertension
• SCD-related chronic kidney disease (CKD)
•  Meet medical criteria to receive (e.g., post-cerebrovascular accident) but are contraindicated for chronic transfusions (e.g., alloimmunization, transfusion reactions)
• Previous experience with Hydroxyurea (HU) use for at least 6 months at the maximum tolerated dose but have shown to be unresponsive and/or intolerant or ineligible AND
• Previous experience with a stable dose of voxelotor, crizanlizumab, or L-glutamine for at least 6 months but have shown to be unresponsive and/or intolerant or ineligible
• Documented SCD at the time of screening (S/S, S/β0 and S/β+ genotypes only).
  Documented HbF ≤ 20% of total Hb.
  Total Hb ≥ 5.5 g/dL and ≤ 12 g/dL (males) or ≤ 10.6 g/dL (females) at screening.
• Participant must meet both of the following laboratory values at screening:
  • Absolute neutrophil count ≥ 1.5 × 10^9 per liter (/L)
  • Platelets ≥ 80 × 10^9/L
  • Absolute reticulocyte count at screening ≥ 100 x 10^9/L. 

• Sickle cell complication requiring care from a medical provider in the 14 days prior to starting study drug.
• History of bone marrow transplant or human stem cell transplant or gene therapies.
• Participants with a history of severe renal disease defined as estimated glomerular filtration rate < 30 mL/min/1.73m^2.
•  Participants on dialysis of any kind are excluded.
• Participants receiving regularly scheduled transfusions or any participant who has been transfused within 60 days prior to initiating study drug.
• Participant with active malignancy, or history of cancer (except for squamous cell skin cancer, basal cell skin cancer, and stage 0 cervical carcinoma in situ, with no recurrence for the last 5 years), or with an immediate family member with known or suspected familial cancer syndrome. 
• Known presence of a chromosomal abnormality or genetic mutation that may put the participant at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Participant currently on HU, voxelotor, crizanlizumab, and/ or L-glutamine or have received HU, voxelotor, crizanlizumab, and/ or L-glutamine within 60 days prior to initiating study drug.