Non–Transfusion-Dependent Alpha- or Beta-Thalassemia MedDRA version: 20.0 Level: LLT Classification code 10074356 Term: Non-transfusion dependent thalassemia System Organ Class: 100000004850
Conditions
Interventions
Product Name: Mitapivat, Mitapivat sulfate
Product Code: [AG-348]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mitapivat
CAS Number: 2151847-10-6
Current Sponsor code: AG-348 sulfate h
Sponsors
AGIOS PHARMACEUTICALS, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 Hb electrophoresis, Hb high-performance liquid chromatography, and/or DNA analysis from the subject's medical record. If this information is not available from the subject's medical record, the test(s) can be performed by a local laboratory during the Screening Period. If a local laboratory is unable to perform the test(s), results from the comprehensive a- and ß-globin genotyping performed by the study central laboratory can be used. 3. Hb concentration =7 days) collected during the Screening Period. 4. Non–transfusion dependent, defined as =16 weeks before randomization. 6. Women of childbearing 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, 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. 7. 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 167 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Pregnant/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 >=18 weeks before randomisation. 5. Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered >=18 weeks before randomisation. 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 =450 msec (males) or >=470 msec (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. AST>2.5 × upper limit of normal (ULN); unless due to hemolysis and hepatic iron deposition and ALT>2.5 × ULN (unless due to hepatic iron deposition) 9. Estimated glomerular filtration rate 440 mg/dL (5 mmol/L). 11. Active infection requiring systemic antimicrobial therapy at the time of providing IC. 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 (HBsAg). 13. Positive test for HIV-1 Ab or HIV-2 Ab. 14. History of major surgery (including splenectomy) =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 half-lives (whichever is longer), before randomisation. 17. Receiving anabolic steroids, that have not been stopped for at least 4 weeks before rando
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of mitapivat versus placebo on anemia in subjects with a- or ß- non–transfusion-dependent thalassemia (NTDT);Secondary Objective: Key Secondary Objectives • To compare the effect of mitapivat versus placebo on fatigue • To compare the effect of mitapivat versus placebo on additional measures of anemia Secondary Objectives • To evaluate the effect of mitapivat versus placebo on anemia and markers of hemolysis and erythropoiesis • To evaluate the effect of mitapivat versus placebo on additional measures of fatigue • To evaluate the effect of mitapivat versus placebo on physical activity • To evaluate the effect of mitapivat versus placebo on iron metabolism • To evaluate the safety of mitapivat • To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat;Primary end point(s): Hemoglobin (Hb) response, defined as a >=1.0 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline;Timepoint(s) of evaluation of this end point: Please refer to the schedule of assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints • Change from baseline in average Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) subscale score from Week 12 through Week 24 • Change from baseline in average Hb concentration from Week 12 through Week 24 Secondary Endpoints • Hb 1.5+ response, defined as a >=1.5 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline • Change from baseline in indirect bilirubin, lactate dehydrogenase, and haptoglobin at Week 24 • Change from baseline in reticulocytes and erythropoietin at Week 24 • Improvement in the Patient Global Impression of Severity (PGIS)-Fatigue by at least 1 category at Weeks 12, 16, 20, and 24 compared with baseline, or "no change" if no or mild fatigue at baseline • Improvement in the Patient Global Impression of Change (PGIC)-Fatigue at Weeks 12, 16, 20, and 24, or "no change" if no or mild fatigue at baseline • Change from baseline in the 6-minute walk test (6MWT) distance at Week 24 • Change from baseline in markers of iron metabolism, including serum ferritin and transferrin saturation, at Week 24 • Type, severity, and relationship of adverse events (AEs) and serious adverse events • Plasma or blood concentrations and pharmacokinetic parameters of mitapivat and pharmacodynamic parameters, including adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG);Timepoint(s) of evaluation of this end point: Please refer to the schedule of assessment | — |
Countries
Brazil, Bulgaria, Canada, Denmark, Egypt, France, Germany, Greece, Italy, Lebanon, Malaysia, Netherlands, Saudi Arabia, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactScientific Communications
Agios Pharmaceuticals, Inc.
Outcome results
None listed