Patients, age 12 to 65 years, with Sickle Cell Disease or thalassemia. Sickle cell Disease, Thalassemia
Conditions
Interventions
This study is a multicenter, Phase 2, open-label, multiple-cohort study examining the safety and efficacy of FT-4202 for the treatment of patients, age 12 to 65 years, with SCD or thalassemia. Three t
at the end of the 48-week treatment period, patients may enroll into a separate open-label extension protocol . The dose of FT-4202 is 400 mg daily (QD) administered continuously
the selection of the starting dose is based on results from a Phase 1 study in patients with SCD who were not receiving chronic RBC transfusions.
Cohort A: Patients with SCD on Chronic RBC Transfusion
Patients will be enrolled into a 48-week treatment period
the selecti
treatment
Sponsors
Forma Therapeutics
Eligibility
Sex/Gender
All
Age
12 Years to 65 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria - All Cohorts Informed Consent 1. Patient has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each patient; in the case of adolescent patients, both the consent of the patient’s legal representative or legal guardian, and the patient’s assent must be obtained) Age 2. Age 12 to 65 years, inclusive, at time of first dose Sex and Contraceptive/Barrier Requirements 3. Patients, who if female and of childbearing potential, are using highly effective methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug. Inclusion Criteria – Cohort Specific Cohort A (SCD Transfusion Cohort) 1. Male or female study patient with a confirmed diagnosis of sickle cell disease ? Documentation of SCD genotype (HbSS, HbSß0-thalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by laboratory testing during Screening 2. Chronically RBC transfused for primary stroke prevention or due to previous stroke. Chronic RBC transfusion is defined as: = 6 RBC units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period 3. Receiving chronic RBC transfusion by straight transfusions 4. At least 24 months of chronic monthly RBC transfusions for primary stroke prevention or treatment of primary stroke (initial completed overt clinical stroke with document infarction on brain computed tomography [CT] or magnetic resonance imaging [MRI]) 5. On iron chelation therapy for > 3 months prior to enrollment 6. Documented adequate monthly transfusions with average HbS = 45% (the upper limit of the established academic community standard) for the previous 12 weeks of RBC transfusions before the first dose of study treatment Cohort B (Thalassemia Transfusion Cohort) 1. Male or female study patients with documented diagnosis of ß-thalassemia, Hemoglobin E/ ß-thalassemia or Hemoglobin H (a-thalassemia) 2. Chronically transfused, defined as: = 6 RBC units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period 3. On iron chelation therapy for > 3 months prior to enrollment Cohort C (Thalassemia Non-transfused Cohort) 1. Male or female study patients with documented diagnosis of ß-thalassemia, Hemoglobin E/ ß-thalassemia or Hemoglobin H (a-thalassemia) 2. Hemoglobin = 10 g/dL
Exclusion criteria
Exclusion criteria: Exclusion Criteria – All Cohorts Medical Conditions 1. Female who is breast feeding or pregnant 2. Hepatic dysfunction characterized by: ? Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) ? Direct bilirubin > 3.0 × ULN ? History of cirrhosis 3. Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection. ? Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay Screening/ enrollment until active therapy has been completed. ? Patients with acute viral infections without available therapies (eg, coronavirus disease 2019 [COVID-19]) should delay Screening/ enrollment until the acute infection has resolved. Note: Infection prophylaxis is allowed (see concomitant medication restrictions). 4. Known human immunodeficiency virus (HIV) positivity 5. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive) 6. Active hepatitis C infection 7. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m2) or on chronic dialysis. 8. History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation. ? Patients with malignancy considered surgically cured are eligible (eg, non- melanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [Stage 1], Grade 1 endometrial cancer) 9. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: ? Unstable angina pectoris or myocardial infarction or elective coronary intervention ? Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, ? Pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, = Grade 3 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (or higher) 10. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable). Prior/Concomitant Therapy 11. Chronic systemic glucocorticoids = 3 months (90 Days) prior to the first dose of study treatment (physiologic replacement therapy for adrenal insufficiency is allowed). Single day glucocorticoid treatment (eg, for prevention or treatment of transfusion reactions, is allowed). 12. Receiving or use of concomitant medications that are strong inducers or moderate/strong inhibitors of cytochrome P450 (CYP)3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study. 13. Use of erythropoietin or other hematopoietic growth factor treatment within 30 days of starting study treatment or anticipated need for such agents during the study. 14. Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy) 15. Initiation of a new chelation therapy within 3 months before the first dose of study treatment Prior/Concurrent Clinical Study Experience 16. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: To assess the erythroid response of FT-4202 in adolescents and adults with SCD or thalassemia;Timepoints: ? Cohorts A and B: Proportion of patients with = 20% reduction in RBC transfusions over a continuous 12-week treatment period versus baseline RBC transfusion history ? Cohort C: Hemoglobin response rate at Week 12 (increase of = 1.0 g/dL from baseline;Measure: reduction in RBC transfusion and Hemoglobin response rate at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: To further assess the safety and clinical activity of FT-4202 in adolescents and adults with SCD or thalassemia;Timepoints: ? Number and percent of patients with SAEs, AEs leading to discontinuation, clinically significant laboratory measurements, and clinically significant abnormal ECGs;Measure: ? Number and percent of patients with SAEs, AEs leading to discontinuation, clinically significant laboratory measurements, and clinically significant abnormal ECGs ? Cohorts A and B: o Proportion of patients with = 33% reduction in RBC transfusion over a continuous 12-week treatment period versus baseline RBC transfusion history o Reduction in RBC transfusions over 12, 24 and 48 weeks ? Cohort C: o Hemoglobin response rate at Week 24 and Week 48 (increase of = 1.0 g/dL from baseline). o Change from baseline in Hb over 12, 24, and 48 weeks;Name: To measure the effects of FT-4202 on measures of iron overload in all patients;Timepoints: Changes in serum ferritin levels at 12, 24, and 48 weeks versus baseline.Changes in liver iron concentration at 48 weeks versus baseline;Measure: Changes in serum ferritin levels at 12, 24, and 48 weeks versus baseline.Changes in liver iron concentration at 48 weeks versus baseline | — |
Contacts
Public ContactAziz Zoghbi
Director of Country Oversight and Manageme nt MENA, Gulf and Africa
Outcome results
None listed