A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary purpose of this study is to compare the effect of mitapivat versus placebo on anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Agios Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

• Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H [HbH] disease) based on Hb electrophoresis, Hb high-performance liquid chromatography (HPLC)), and/or deoxyribonucleic acid (DNA) analysis;

• Hb concentration ≤10.0 grams per deciliter (g/dL) (100.0 grams per liter [g/L]), based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period;

• Non-transfusion-dependent, defined as ≤5 red blood cell (RBC) units during the 24-week period before randomization; and no RBC transfusions ≤8 weeks before providing informed consent or during the Screening Period;

• If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization;

• Women of child-bearing potential (WOCBP) and men with partners who are WOCBP must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, one of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug for women and 90 days after the last dose of study drug for men. The second form of contraception can be an acceptable barrier method;

• Written informed consent before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.

Exclusion Criteria:

• Pregnant or breastfeeding;

• Documented history of homozygous or heterozygous sickle hemoglobin (HbS) or hemoglobin C (HbC);

• Prior exposure to gene therapy or prior bone marrow or stem cell transplantation;

• Currently receiving treatment with luspatercept; the last dose must have been administered ≥18 weeks before randomization;

• Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization;

• History of any malignancy, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ. Participants must not have active disease or received anticancer treatment ≤5 years before providing informed consent;

• History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent;

• Hepatobiliary disorders;

• Estimated glomerular filtration rate <45 milliliters per minute (mL/min)/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation;

• Nonfasting triglycerides >440 milligrams per deciliter (mg/dL) (5 millimoles per liter [mmol/L]);

• Active infection requiring systemic antimicrobial therapy at the time of providing informed consent;

• Positive test for hepatitis C virus antibody (HCVAb) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);

• Positive test for human immunodeficiency virus (HIV)-1 antibody (Ab) or HIV-2 Ab;

• History of major surgery (including splenectomy) ≤16 weeks before providing informed consent and/or a major surgical procedure planned during the study;

• Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a timeframe equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device;

• Receiving strong CYP3A4/5 inhibitors that have not been stopped for ≥5 days or a timeframe equivalent to 5 half-lives (whichever is longer); or strong CYP3A4 inducers that have not been stopped for ≥4 weeks or a timeframe equivalent to 5 half-lives (whichever is longer), before randomization;

• Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed. The testosterone dose and preparation must be stable for ≥10 weeks before randomization;

• Known allergy to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate);

• Any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data.