Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Pociredir

Korábbi kezelés

• Sickle cell complication requiring care from a medical provider in hospital or emergency care setting in the 14 days prior to starting study drug.
• Participants receiving regularly scheduled transfusions or therapeutic phlebotomies, or any participant who has been transfused within 60 days prior to initiating study drug.
• Participant currently on HU, or have received HU, within 60 days prior to initiating study drug.

Más betegség

• 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.
• 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 has 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 is 18 to 65 years of age, inclusive at the time informed consent is obtained.
• Documented SCD at the time of screening (S/S, S/β0, S/β+, and S/C only) as confirmed through review of medical records or HPLC.
• Participants who meet at least one the following criteria:
  • ≥4 to 10 episodes of SCD pain crisis over 12 months, or ≥2 to 5 over 6 months prior to screening
  • ≥2 episodes of SCD pain crisis plus at least one of the following over previous 12 months: i) Acute chest syndrome (ACS) ii. Hepatic or splenic sequestration iii. Priapism
  • ≥2 of the following events over the previous 12 months:i. ACS ii. Hepatic or splenic sequestration iii. Priapism
  • Tricuspid regurgitant jet velocity (TRV) ≥ 3.0 meter/second(m/s) OR TRV ≥ 2.5 m/s + N-terminal pro b-type natriuretic peptide (NT-proBNP) plasma level ≥ 160 picogram per milliliter; OR documented ongoing pulmonary hypertension diagnosed from previous echocardiogram or right-sided heart catheterization with mean pulmonary artery pressure > 25 millimeter of mercury;
  • 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) but have shown to be unresponsive and/or intolerant or ineligible AND
• Previous experience with a stable dose of voxelotor, crizanlizumab, and/ or L-glutamine but have shown to be unresponsive and/or intolerant or ineligible
• Per Investigator's recommendation, participants may continue crizanlizumab and/or L-glutamine but must be on a stable dose for at least 6 months
• 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.