Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Pociredir

February 11, 2026 updated by: Fulcrum Therapeutics

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Participants will receive 12 weeks of dosing with 4 weeks of follow-up. Approximately 10 participants will be enrolled in each cohort. A maximum of 3 participants with SCD HbSC+ genotype may be enrolled in each cohort.

Cohort 1 will receive 6 milligrams (mg) of Pociredir by mouth once daily. Doses for subsequent cohorts will be determined following review by the Data Monitoring Committee [DMC]. A total of seven cohorts may be included. 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. Additional cohorts using alternative dosing schedules may be considered based on available data.

The primary endpoints of the study are to evaluate the safety and tolerability of Pociredir as measured by the frequency of adverse events and to evaluate single and multiple-dose pharmacokinetics of Pociredir in participants with sickle cell disease. Secondary endpoints include evaluating the effect of Pociredir on fetal hemoglobin induction in peripheral blood and evaluating the effects of Pociredir on hemolysis in participants with sickle cell disease.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nigeria
      • Abuja, Nigeria, 900247
        • National Hospital, Abuja
      • Ibadan, Nigeria, 200212
        • University of Ibadan
      • Kaduna, Nigeria, 800125
        • Barau Dikko Teaching Hospital
  • South Africa
      • Johannesburg, South Africa, 2193
        • Charlotte Maxeke Johannesburg Academic Hospital
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences (UAMS)
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
    • Georgia
      • Atlanta, Georgia, United States, 30315
        • Sonar Research Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Chicago
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
        • Our Lady of the Lake Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • New York
      • Jamaica, New York, United States, 11432
        • Queens Hospital Cancer Center
      • The Bronx, New York, United States, 10461
        • Jacobi Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
      • Greenville, North Carolina, United States, 27834
        • Eastern Carolina University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Lynn Health Science Institute
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas Houston
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

    1. ≥4 to 10 episodes of SCD pain crisis over 12 months, or ≥2 to 5 over 6 months prior to screening
    2. ≥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
    3. ≥2 of the following events over the previous 12 months:i. ACS ii. Hepatic or splenic sequestration iii. Priapism
    4. 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;
    5. SCD-related chronic kidney disease (CKD)
    6. 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:

    1. Absolute neutrophil count ≥ 1.5 × 10^9 per liter (/l)
    2. Platelets ≥ 80 × 10^9/l
    3. Absolute reticulocyte count at screening ≥ 100 x 10^9/l.

Key Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pociredir oral capsule(s) in Sickle Cell participants
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)
Participants will receive Pociredir
Other Names:
  • FTX-6058

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-Emergent Adverse Events
Time Frame: Up to approximately 16 weeks of monitoring
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
Time Frame: Days 1, 14, 28, 42, 56, 70, 84 and 91
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Red cell distribution width
Time Frame: Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91
Blood samples will be collected for the analysis of hematology parameter: red cell distribution width
Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91
Change from Baseline in unconjugated bilirubin
Time Frame: Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91
Blood samples will be collected for the analysis of clinical chemistry parameter: unconjugated bilirubin
Baseline and at Days 1, 14, 28, 42, 56, 70, 84 and 91
Change from Baseline in percentage fetal hemoglobin (%HbF) biomarkers in peripheral blood
Time Frame: Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112
The percentage of HbF will be measured in peripheral whole blood.
Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112
Change from Baseline in % Reticulocytes
Time Frame: Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112
The percentage of reticulocytes will be measured in peripheral whole blood.
Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112
Change from Baseline in Absolute Reticulocyte Count
Time Frame: Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112
The absolute reticulocyte count will be measured in peripheral whole blood.
Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 91, and 112

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fulcrum Therapeutics

Investigators

  • Study Director: Adeyemi Adenola, MD, Fulcrum Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2021

Primary Completion (Actual)

January 20, 2026

Study Completion (Actual)

January 20, 2026

Study Registration Dates

First Submitted

December 14, 2021

First Submitted That Met QC Criteria

December 23, 2021

First Posted (Actual)

December 27, 2021

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 11, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6058-SCD-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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