Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Pociredir

About

Brief Summary

This is a study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of Pociredir in participants with sickle cell disease.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

65 Years

Key Inclusion Criteria:

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 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: 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
Participants who previously received voxelotor, crizanlizumab, and/ or L-glutamine and will be discontinuing before starting dosing with pociredir:
- Must be off voxelotor and crizanlizumab for at least 60 days prior to initiating study drug; and
- Must be off L-glutamine for at least 24-hours prior to initiating study drug.
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.

Key Exclusion Criteria:

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 therapeutic phlebotomies, or any participant who has been transfused.
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 currently on HU, or have received HU, within 60 days prior to initiating study drug.

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