Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Pociredir

NCT ID: NCT05169580

Last Updated: 2025-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-13

Study Completion Date

2026-01-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Sickle Cell Disease Sickle Cell Anemia

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Open-label, multiple-dose study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Pociredir oral capsule(s)

Intervention Type DRUG

Participants will receive Pociredir

Interventions

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Pociredir oral capsule(s)

Participants will receive Pociredir

Intervention Type DRUG

Other Intervention Names

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FTX-6058

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fulcrum Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Adeyemi Adenola, MD

Role: STUDY_DIRECTOR

Fulcrum Therapeutics

Locations

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University of Arkansas for Medical Sciences (UAMS)

Little Rock, Arkansas, United States

Site Status RECRUITING

University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Foundation for Sickle Cell Disease Research, LLC

Hollywood, Florida, United States

Site Status WITHDRAWN

University of Miami Health System

Miami, Florida, United States

Site Status WITHDRAWN

Sonar Research Center

Atlanta, Georgia, United States

Site Status RECRUITING

Visionaries Clinical Research

Atlanta, Georgia, United States

Site Status WITHDRAWN

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Site Status WITHDRAWN

Augusta University

Augusta, Georgia, United States

Site Status WITHDRAWN

University of Illinois Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Our Lady of the Lake Hospital

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Axon Clinical Research Institute

Baltimore, Maryland, United States

Site Status WITHDRAWN

Boston Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States

Site Status WITHDRAWN

Queens Hospital Cancer Center

Jamaica, New York, United States

Site Status RECRUITING

Jacobi Medical Center

The Bronx, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Eastern Carolina University

Greenville, North Carolina, United States

Site Status RECRUITING

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

University of Texas Houston

Houston, Texas, United States

Site Status RECRUITING

Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

National Hospital, Abuja

Abuja, , Nigeria

Site Status RECRUITING

University of Ibadan

Ibadan, , Nigeria

Site Status RECRUITING

Barau Dikko Teaching Hospital

Kaduna, , Nigeria

Site Status RECRUITING

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, , South Africa

Site Status RECRUITING

Countries

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United States Nigeria South Africa

Central Contacts

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Call Center

Role: CONTACT

617-651-8853

References

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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.

Reference Type BACKGROUND
PMID: 24222332 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40569673 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22017641 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28423290 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23209159 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24361300 (View on PubMed)

Other Identifiers

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6058-SCD-101

Identifier Type: -

Identifier Source: org_study_id

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