Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Pociredir

NCT05169580 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 6058-SCD-101
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 18

Brief Summary

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

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

Sickle Cell Disease; Sickle Cell Anemia; Pharmacokinetics; Pharmacodynamics; Pociredir; Open label

Outcome Measures

Primary Outcomes (2)

• Treatment-Emergent Adverse Events

  To evaluate the safety and tolerability of Pociredir in adult participants with sickle cell disease based on the frequency of adverse events (AEs) and changes in clinically significant laboratory test results, vital signs and electrocardiograms (ECGs) parameters.

  Up to approximately 16 weeks of monitoring

• Plasma Concentrations of Pociredir

  Blood samples will be collected to measure the plasma concentration of Pociredir at specified timepoints.

  Days 1, 14, 28, 42, 56, 70, 84 and 91

Secondary Outcomes (5)

• Change from Baseline in percentage fetal hemoglobin (%HbF) biomarkers in peripheral blood

  Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112

• Change from Baseline in % Reticulocytes

  Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112

• Change from Baseline in Absolute Reticulocyte Count

  Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112

• Change from Baseline in Red cell distribution width

  Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91

• Change from Baseline in unconjugated bilirubin

  Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91

Study Arms (1)

Pociredir oral capsule(s) in Sickle Cell participants

EXPERIMENTAL

Cohort 1 will receive 6 mg of Pociredir by mouth once daily. Cohort 2 will be dosed at 2 mg once daily by mouth, and cohort 3 will be dosed at 12 mg once daily by mouth. The Sponsor will reinitiate enrolment in the 3rd cohort (12 mg cohort) with the updated inclusion and exclusion criteria. Based on review of available safety and biomarker data and with the recommendation of the DMC, a subsequent 4th cohort of 20 mg and potentially a 5th cohort of 30 mg may be initiated. A total of seven cohorts may be included. Following the first cohort, doses for all subsequent cohorts will be determined following DMC review of the safety and pharmacokinetic data observed in participants from the prior and ongoing cohorts. Alternate dosing schedules may be evaluated in some of the cohorts.

Drug: Pociredir oral capsule(s)

Interventions

Pociredir oral capsule(s) DRUG

Participants will receive Pociredir

Also known as: FTX-6058

Pociredir oral capsule(s) in Sickle Cell participants

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Sickle cell complication requiring care from a medical provider in hospital or emergency care setting 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 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 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.

Sponsors & Collaborators

• Fulcrum Therapeutics: lead

Study Sites (18)

University of Arkansas for Medical Sciences (UAMS)

Little Rock, Arkansas, 72205, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Sonar Research Center

Atlanta, Georgia, 30315, United States

Location

University of Illinois Chicago

Chicago, Illinois, 60612, United States

Location

Our Lady of the Lake Hospital

Baton Rouge, Louisiana, 70808, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Queens Hospital Cancer Center

Jamaica, New York, 11432, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Eastern Carolina University

Greenville, North Carolina, 27834, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

University of Texas Houston

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

National Hospital, Abuja

Abuja, 900247, Nigeria

Location

University of Ibadan

Ibadan, 200212, Nigeria

Location

Barau Dikko Teaching Hospital

Kaduna, 800125, Nigeria

Location

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, 2193, South Africa

Location

Related Publications (6)

• Ngo DA, Aygun B, Akinsheye I, Hankins JS, Bhan I, Luo HY, Steinberg MH, Chui DH. Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin. Br J Haematol. 2012 Jan;156(2):259-64. doi: 10.1111/j.1365-2141.2011.08916.x. Epub 2011 Oct 24.

  PMID: 22017641 BACKGROUND

• Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med. 2017 Apr 20;376(16):1561-1573. doi: 10.1056/NEJMra1510865. No abstract available.

  PMID: 28423290 BACKGROUND

• Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a011643. doi: 10.1101/cshperspect.a011643.

  PMID: 23209159 BACKGROUND

• Saraf SL, Molokie RE, Nouraie M, Sable CA, Luchtman-Jones L, Ensing GJ, Campbell AD, Rana SR, Niu XM, Machado RF, Gladwin MT, Gordeuk VR. Differences in the clinical and genotypic presentation of sickle cell disease around the world. Paediatr Respir Rev. 2014 Mar;15(1):4-12. doi: 10.1016/j.prrv.2013.11.003. Epub 2013 Nov 15.

  PMID: 24361300 BACKGROUND

• Steinberg MH, Chui DH, Dover GJ, Sebastiani P, Alsultan A. Fetal hemoglobin in sickle cell anemia: a glass half full? Blood. 2014 Jan 23;123(4):481-5. doi: 10.1182/blood-2013-09-528067. Epub 2013 Nov 12.

  PMID: 24222332 BACKGROUND

• Abbasi M, Srivastava A, Saraf SL. Management of Kidney Disease with Sickle Cell Disease. J Am Soc Nephrol. 2025 Oct 1;36(10):2041-2054. doi: 10.1681/ASN.0000000804. Epub 2025 Jun 26.

  PMID: 40569673 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Adeyemi Adenola, MD

  Fulcrum Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, multiple-dose study.

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: December 27, 2021
• Study Start: December 13, 2021
• Primary Completion: January 20, 2026
• Study Completion: January 20, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

NG (3); US (14); ZA (1)