A study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE-T)
- Conditions
- Transfusion-Dependent Alpha- or Beta-ThalassemiaMedDRA version: 22.0Level: LLTClassification code 10081904Term: Transfusion dependent thalassemiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2021-000212-34-ES
- Lead Sponsor
- Agios Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 240
1. =18 years of age at the time of providing informed consent.
2. Documented diagnosis of thalassemia (ß-thalassemia with or without a-globin gene
mutations, HbE/ß-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 ß-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) 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 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 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.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 234
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
1. Pregnant or breastfeeding.
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 administration of the first dose of study drug.
5. Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered =36 weeks before administration of the first dose of study drug.
6. 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.
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, 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 (whichever is longer), or strong CYP3A4 inducers that have not been stopped for =4 weeks or a time frame equivalent to 5
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To compare the effect of mitapivat versus placebo on transfusion burden in subjects<br>with a- or ß-transfusion dependent thalassemia (TDT);Primary end point(s): • Transfusion reduction response (TRR), defined as a =50% reduction in transfused red blood cell (RBC) units with a reduction of =2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline;Secondary Objective: • To compare the durability of the effect of mitapivat versus placebo on transfusion burden<br>• To evaluate the effect of mitapivat versus placebo on additional measures of transfusion burden<br>• To evaluate the effect of mitapivat versus placebo on iron metabolism<br>• To evaluate the safety of mitapivat<br>• To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat;Timepoint(s) of evaluation of this end point: Please refer to the schedule of assessment
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Please refer to the schedule of assessment;Secondary end point(s): • =33% reduction in transfused RBC units from Week 13 through Week 48 compared with baseline (TRR3)<br>• =50% reduction in transfused RBC units in any consecutive 24-week period through Week 48 compared with baseline (TRR2)<br>• =50% reduction in transfused RBC units from Week 13 through Week 48 compared with baseline (TRR4)<br>• Change from baseline in transfused RBC units from Week 13 through Week 48<br>• Transfusion independence, defined as transfusion-free for =8 consecutive weeks through Week 48<br>• Change from baseline in iron, serum ferritin, total iron binding capacity, and transferrin saturation through Week 48<br>• Type, severity, and relationship of adverse events (AEs) and serious adverse events<br>• Plasma or blood concentrations and pharmacokinetic parameters of mitapivat and pharmacodynamic parameters, including adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG)