Overview

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

Status:
Recruiting
Trial end date:
2024-06-01
Target enrollment:
0
Participant gender:
All
Summary
The primary purpose of this study is to compare the effect of mitapivat versus placebo on transfusion burden in participants with transfusion-dependent alpha- or beta-thalassemia (TDT).
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 deoxyribonucleic acid (DNA) analysis;

- Considered transfusion-dependent, defined as 6 to 20 RBC units transfused and ≤6-week
transfusion-free period during the 24-week period before randomization;

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

- Women of childbearing potential (WOCBP) and men with partners who are WOCBP must be
abstinent of sexual activities that may induce pregnancy as part of their usual
lifestyle or agree to use two 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 (Hb S) or
hemoglobin C (Hb C);

- 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 ≥36 weeks before randomization;

- Currently receiving treatment with hematopoietic stimulating agents; the last dose
must have been administered ≥36 weeks before randomization;

- History of any malignancy, except for nonmelanomatous skin cancer in situ, cervical
carcinoma in situ, or breast carcinoma in situ. Subjects 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 meter
(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) ≤6 months 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 ≥12 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.