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Trial record 1 of 1 for:    NCT04770779
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A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) (ENERGIZE-T)

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ClinicalTrials.gov Identifier: NCT04770779
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : May 11, 2022
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief 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).

Condition or disease Intervention/treatment Phase
Transfusion-dependent Alpha-Thalassemia Transfusion-dependent Beta-Thalassemia Drug: Placebo Matching Mitapivat Drug: Mitapivat Phase 3

Detailed Description:
The mitapivat group will include approximately 160 participants. The placebo group will include approximately 80 participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : November 30, 2021
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024


Arm Intervention/treatment
Experimental: Mitapivat

Double-Blind Period: Participants will receive mitapivat 100 milligrams (mg) orally, twice daily (BID) for 48 weeks.

Open-label Extension Period: Participants who do not discontinue study drug may choose to continue to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Drug: Mitapivat
Tablets
Other Names:
  • AG-348
  • AG-348 sulfate hydrate
  • Mitapivat sulfate

Placebo Comparator: Placebo

Double-Blind Period: Participants will receive placebo matching mitapivat orally, BID for 48 weeks.

Open-label Extension Period: Participants who do not discontinue study drug may choose to receive mitapivat for up to an additional 5 years after the Double-blind Period.

Drug: Placebo Matching Mitapivat
Tablets

Drug: Mitapivat
Tablets
Other Names:
  • AG-348
  • AG-348 sulfate hydrate
  • Mitapivat sulfate




Primary Outcome Measures :
  1. Percentage of Participants With Transfusion Reduction Response (TRR) [ Time Frame: Baseline up to Week 48 ]
    TRR is defined as ≥50% reduction in transfused red blood cells (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline.


Secondary Outcome Measures :
  1. Percentage of Participants With ≥33% Reduction in Transfused RBC Units From Week 13 Through Week 48 Compared With Baseline [ Time Frame: Baseline, Week 13 up to Week 48 ]
  2. Percentage of Participants With ≥50% Reduction in Transfused RBC Units in Any Consecutive 24-week Period Through Week 48 Compared With Baseline [ Time Frame: Baseline up to Week 48 ]
  3. Percentage of Participants With ≥50% Reduction in Transfused RBC Units From Week 13 Through Week 48 Compared With Baseline [ Time Frame: Baseline, Week 13 up to Week 48 ]
  4. Change From Baseline in Transfused RBC Units From Week 13 Through Week 48 [ Time Frame: Baseline, Week 13 up to Week 48 ]
  5. Percentage of Participants With Transfusion-Independence [ Time Frame: Up to Week 48 ]
    Transfusion-independence is defined as transfusion-free for ≥8 consecutive weeks through Week 48.

  6. Change From Baseline in Iron Through Week 48 [ Time Frame: Baseline, Week 48 ]
  7. Change From Baseline in Serum Ferritin Through Week 48 [ Time Frame: Baseline, Week 48 ]
  8. Change From Baseline in Total Iron Binding Capacity Through Week 48 [ Time Frame: Baseline, Week 48 ]
  9. Change From Baseline in Transferrin Saturation Through Week 48 [ Time Frame: Baseline, Week 48 ]
  10. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 317 ]
  11. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Graded by Severity [ Time Frame: Up to Week 317 ]
    AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03) from Grades 1 to 4 where Grade 1 is mild and Grade 4 is life-threatening.

  12. Percentage of Participants with Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug [ Time Frame: Up to Week 317 ]
  13. Percentage of Participants with Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug [ Time Frame: Up to Week 317 ]
  14. Plasma or Blood Concentrations Over Time for Mitapivat [ Time Frame: Pre-dose Week 12; pre-dose Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]
  15. Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]
  16. Maximum Plasma Concentration (Cmax) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]
  17. Time of Maximum Plasma Concentration (Tmax) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]
  18. Blood Concentration of Adenosine Triphosphate (ATP) [ Time Frame: Pre-dose Day 1; pre-dose Week 12; pre-dose Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]
  19. Blood Concentration of 2,3 - diphosphoglycerate (2,3-DPG) [ Time Frame: Pre-dose Day 1; pre-dose Week 12; pre-dose Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04770779


Contacts
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Contact: Medical Affairs 833-228-8474 medinfo@agios.com

Locations
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Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
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Study Chair: Medical Affairs Agios Pharmaceuticals, Inc.
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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04770779    
Other Study ID Numbers: AG348-C-018
2021-000212-34 ( EudraCT Number )
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: May 11, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
alpha-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn