A Phase 3, Double-blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE-T)
- Conditions
- &alfa- or &beta- transfusion-dependent thalassemia10038158
- Registration Number
- NL-OMON56084
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 21
1. >=18 years of age at the time of providing informed consent.
2. Documented diagnosis of thalassemia (β-thalassemia with or without a-globin
gene
mutations, HbE/β-thalassemia, or a-thalassemia/HbH disease) based on DNA
analysis
from the subject*s medical record. If this information is not available from
the subject*s
medical record, DNA analysis can be performed by a local laboratory during the
Screening Period. If a local laboratory is unable to perform the test, results
from the
comprehensive a- and β-globin genotyping performed by the study central
laboratory can
be used.
3. Transfusion dependent, defined as 6 to 20 RBC units transfused and a <=6-week
transfusion-free period during the 24-week period before randomization.
4. If taking hydroxyurea, the hydroxyurea dose must be stable for >=16 weeks
before
randomization.
5. Women of childbearing potential (WOCBP) must be abstinent of sexual
activities that may induce pregnancy as part of their usual
lifestyle or agree to use 2 forms of contraception, 1 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.
6. Written informed consent before any study-related procedures are conducted
and willing
to comply with all study procedures for the duration of the study.
1. Pregnant, breastfeeding or parturient.
2. Documented history of homozygous or heterozygous HbS or HbC.
3. Prior exposure to gene therapy or prior bone marrow or stem cell
transplantation.
4. Currently receiving treatment with luspatercept; the last dose must have
been administered >=36 weeks before randomization.
5. Currently receiving treatment with hematopoietic stimulating agents; the
last dose must have been administered >=36 weeks before randomization.
6. History of malignancy (active or treated) <=5 years before providing informed
consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in
situ, or breast carcinoma in situ.
7. History of active and/or uncontrolled cardiac or pulmonary disease <=6 months
before providing informed consent, including but not limited to:
a. New York Heart Association Class III or IV heart failure or clinically
significant dysrhythmia
b. Myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or
thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism
c. Heart rate-corrected QT interval using Fridericia*s method >=450 milliseconds
(males) or >=470 milliseconds (females), except for right or left bundle branch
block
d. Severe pulmonary fibrosis as defined by severe hypoxia, evidence of
right-sided heart failure, and radiographic pulmonary fibrosis >50%
e. Severe pulmonary hypertension as defined by severe symptoms associated with
hypoxia, right-sided heart failure, and oxygen indicated
8. Hepatobiliary disorders, including but not limited to:
a. Liver disease with histopathological evidence of cirrhosis or severe fibrosis
b. Clinically symptomatic cholelithiasis or cholecystitis (prior
cholecystectomy is not exclusionary)
c. History of drug-induced cholestatic hepatitis
d. Aspartate aminotransferase >2.5 × upper limit of normal (ULN); unless due to
hemolysis and hepatic iron deposition) and alanine aminotransferase >2.5 × ULN
(unless due to hepatic iron deposition)
9. Estimated glomerular filtration rate <45 mL/min/1.73 m2 by Chronic Kidney
Disease Epidemiology Collaboration creatinine equation.
10. Nonfasting triglycerides >440 mg/dL (5 mmol/L).
11. Active infection requiring systemic antimicrobial therapy at the time of
providing informed consent. If antimicrobial therapy is required during the
Screening Period, screening procedures should not be performed while
antimicrobial therapy is being administered, and the last dose of antimicrobial
therapy must be administered >=7 days before randomization.
12. Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of
active HCV infection, or positive test for hepatitis B surface antigen.
13. Positive test for HIV-1 Ab or HIV-2 Ab.
14. History of major surgery (including splenectomy) <=6 months before providing
informed consent and/or a major surgical procedure planned during the study.
15. Current enrollment or past participation (<=12 weeks before administration
of the first dose of study drug or a time frame equivalent to 5 half-lives of
the investigational treatment, whichever is longer) in any other clinical study
involving an investigational treatment or device.
16. Receiving strong cytochrome P450 (CYP)3A4/5 inhibitors that have not been
stopped for >=5 days or a time frame equivalent to 5 half-lives (
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is to compare the effect of mitapivat versus placebo on<br /><br>anemia in subjects with a- or β-transfusion-dependent thalassemia. The primary<br /><br>endpoint is transfusion reduction response (TRR), defined as a >=50% reduction<br /><br>in transfused red blood cell (RBC) units with a reduction of >=2 units of<br /><br>transfused RBCs in any consecutive 12-week period through Week 48 compared with<br /><br>baseline.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary objective is to compare the durability of the effect of<br /><br>mitapivat versus placebo on transfusion burden.<br /><br>Other secondary objectives are to evaluate the effect of mitapivat versus<br /><br>placebo on additional measures of transfusion burden, to evaluate the effect of<br /><br>mitapivat versus placebo on iron metabolism, to evaluate the safety of<br /><br>mitapivat and to evaluate the pharmacokinetic and pharmacodynamic effects of<br /><br>mitapivat<br /><br></p><br>