Sickle Cell Disease Clinical Trial
Official title:
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 FTX-6058 in participants with sickle cell disease.
Status | Recruiting |
Enrollment | 70 |
Est. completion date | April 2025 |
Est. primary completion date | April 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Key Inclusion Criteria: - Participant is 18 to 65 years of age, inclusive at the time informed consent is obtained. - Participants who meet at least one the following criteria: 1. =4 episodes of SCD pain crisis over 12 months, or =2 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 c. =2 of the following events over the previous 12 months: i. ACS ii. Hepatic or splenic sequestration iii. Priapism d. SCD-related pulmonary arterial hypertension e. SCD-related chronic kidney disease (CKD) f. 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) use for at least 6 months at the maximum tolerated dose but have shown to be unresponsive and/or intolerant or ineligible AND - Previous experience with a stable dose of voxelotor, crizanlizumab, or L-glutamine for at least 6 months but have shown to be unresponsive and/or intolerant or ineligible - Documented SCD at the time of screening (S/S, S/ß0 and S/ß+ genotypes only). - Documented 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 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 with 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, voxelotor, crizanlizumab, and/ or L-glutamine or have received HU, voxelotor, crizanlizumab, and/ or L-glutamine within 60 days prior to initiating study drug. |
Country | Name | City | State |
---|---|---|---|
United States | Atlanta Center for Medical Research | Atlanta | Georgia |
United States | Visionaries Clinical Research | Atlanta | Georgia |
United States | Augusta University | Augusta | Georgia |
United States | Axon Clinical Research Institute | Baltimore | Maryland |
United States | Jacobi Medical Center | Bronx | New York |
United States | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
United States | Foundation for Sickle Cell Disease Research, LLC | Hollywood | Florida |
United States | University of Miami Health System | Miami | Florida |
United States | Lynn Health Science Institute | Oklahoma City | Oklahoma |
United States | Virginia Commonwealth University | Richmond | Virginia |
Lead Sponsor | Collaborator |
---|---|
Fulcrum Therapeutics |
United States,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Treatment-Emergent Adverse Events | To evaluate the safety and tolerability of FTX-6058 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 | |
Primary | Plasma Concentrations of FTX-6058 | Blood samples will be collected to measure the plasma concentration of FTX-6058 at specified timepoints. | Days 1, 14, 28, 42, 56, 70, 84, 88 and 91 | |
Secondary | Change from Baseline in percentage fetal hemoglobin (%HbF) biomarkers in peripheral blood | The percentage of HbF will be measured in peripheral whole blood by high performance liquid chromatography (HPLC). | Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 88, 91, and 112 | |
Secondary | Change from Baseline in % Reticulocytes | The percentage of reticulocytes will be measured in peripheral whole blood by flow cytometry. | Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 88, 91, and 112 | |
Secondary | Change from Baseline in Absolute Reticulocyte Count | The absolute reticulocyte count will be measured in peripheral whole blood by microscopy/cytometry. | Baseline and at Days 1, 14, 28, 42, 56, 70, 84, 88, 91, and 112 | |
Secondary | Change from Baseline in Red cell distribution width | 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 | |
Secondary | Change from Baseline in unconjugated bilirubin | 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 |
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