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A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Not Recruiting
Trial ID: NCT04770753
Purpose
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).
Official Title
A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE)
Stanford Investigator(s)
May Chien
Clinical Assistant Professor, Medicine - Hematology Clinical Assistant Professor, Pediatrics - Hematology & Oncology
Eligibility
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 and no RBC transfusions during the Screening Period;
- If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before
randomization;
- Women of child-bearing potential (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. 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, breastfeeding, or parturient
- 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 malignancy, (active or treated) ≤5 years before providing informed consent;
- History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before
providing informed consent, except for nonmelanomatous skin cancer in situ, cervical
carcinoma in situ, or breast carcinoma in situ;
- 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,
Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and
FD&C Blue #2]);
- 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 Also excluded are:
- Participants who are institutionalized by regulatory or court order
- Participants with any condition(s) that could create undue influence (including
but not limited to incarceration, involuntary psychiatric confinement, and
financial or familial affiliation with the Investigator or Sponsor)
Intervention(s):
drug: Placebo Matching Mitapivat
drug: Mitapivat
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305