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)

ClinicalTrials.gov processed this data on November 13, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING (See Contacts and Locations)
Verified November 2024 by Agios Pharmaceuticals, Inc.

Sponsor

Agios Pharmaceuticals, Inc.

Information Provided by (Responsible Party)

Agios Pharmaceuticals, Inc.

Clinicaltrials.gov Identifier

NCT04770779
Other Study ID Numbers: AG348-C-018
First Submitted: February 18, 2021
First Posted: February 25, 2021
Last Update Posted: November 15, 2024
Last Verified: November 2024
History of Changes

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Study Description

The mitapivat group will include approximately 160 participants. The placebo group will include approximately 80 participants.
Condition or Disease Intervention/Treatment
  • Transfusion-dependent Alpha-Thalassemia
  • Transfusion-dependent Beta-Thalassemia
  • Drug: Placebo Matching Mitapivat
  • Drug: Mitapivat

Study Design

Study TypeInterventional
Actual Enrollment258 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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)
Study Start DateNovember 30, 2021
Actual Primary Completion DateApril 11, 2024
Anticipated Study Completion DateJune 2029

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • 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
    • 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

      Outcome Measures

      Primary Outcome Measures

      1. Percentage of Participants With Transfusion Reduction Response (TRR) [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 [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 [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 [Baseline, Week 13 up to Week 48]
      4. Change From Baseline in Transfused RBC Units From Week 13 Through Week 48 [Baseline, Week 13 up to Week 48]
      5. Percentage of Participants With Transfusion-Independence [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 [Baseline, Week 48]
      7. Change From Baseline in Serum Ferritin Through Week 48 [Baseline, Week 48]
      8. Change From Baseline in Total Iron Binding Capacity Through Week 48 [Baseline, Week 48]
      9. Change From Baseline in Transferrin Saturation Through Week 48 [Baseline, Week 48]
      10. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Week 317]
      11. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Graded by Severity [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 [Up to Week 317]
      13. Percentage of Participants with Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug [Up to Week 317]
      14. Plasma or Blood Concentrations Over Time for Mitapivat [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 [Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36]
      16. Maximum Plasma Concentration (Cmax) of Mitapivat [Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36]
      17. Time of Maximum Plasma Concentration (Tmax) of Mitapivat [Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36]
      18. Blood Concentration of Adenosine Triphosphate (ATP) [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) [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]

      Eligibility Criteria

      Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
      Sexes Eligible for Study All
      Accepts Healthy Volunteers No
      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) 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. 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 (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 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;
      • 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, or other contraindication, 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).

      Contacts and Locations

      Sponsors and Collaborators Agios Pharmaceuticals, Inc.
      Locations
      • Phoenix Children's Hospital | Phoenix, Arizona, United States, 85016-7710
      • San Diego Hospital, UC San Diego Health | La Jolla, California, United States, 92093
      • Children's Hospital Oakland | Oakland, California, United States, 94609-1809
      • Stanford Medicine | Palo Alto, California, United States, 94304-1601
      • Boston Children's Hospital | Boston, Massachusetts, United States, 02115
      • Dana Faber Cancer Institute | Boston, Massachusetts, United States, 02215
      • Children's Hospital of Michigan | Detroit, Michigan, United States, 48201-2196
      • Weill Cornell Medical Center | New York, New York, United States, 10065-4870
      • Duke University Medical Center | Durham, North Carolina, United States, 27710-3038
      • Penn Medicine - University of Pennsylvania Health System | Philadelphia, Pennsylvania, United States, 19104
      • Seattle Cancer Care Alliance, University of Washington | Seattle, Washington, United States, 98101
      • Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP | Ribeirão Preto, Brazil, 14051-260
      • GSH Banco de Sangue de São Paulo | São Paulo, Brazil, 04006-002
      • MHAT "Dr. Nikola Vasiliev" AD | Kyustendil, Bulgaria, 2500
      • UMHAT "Dr. Georgi Stranski" Pleven | Pleven, Bulgaria, 5800
      • UMHAT "Sveti Georgi" EAD | Plovdiv, Bulgaria, 4002
      • SHATHD Sofia | Sofia, Bulgaria, 1756
      • UMHAT "Prof. Dr. Stoyan Kirkovich" | Stara Zagora, Bulgaria, 6000
      • Foothills Medical Centre | Calgary, Alberta, Canada, T2N 2T9
      • Toronto General Hospital, University Health Network | Toronto, Ontario, Canada, M5G 2C4
      • Rigshospitalet | Hovedstaden, Denmark, 2100
      • CHU Hôpital Henri Mondor | Créteil, France, 94010
      • Hôpital Edouard Herriot, CHU de Lyon | Lyon, France, 69003
      • CHU Hôpital de la Timone | Marseille, France, 13385
      • Hôpital Necker Enfants Malades | Paris, France, 75015
      • Charité - UB - CVK - Medizinische Klinik | Berlin, Germany, 13353
      • Universitätsklinikum Essen | Essen, Germany, 45122
      • Universitätsklinikum Leipzig | Leipzig, Germany, 04103
      • University General Hospital of Patras | Achaia, Greece, 26504
      • Children's Hospital Agia Sophia, National and Kapodistrian University of Athens Medical School | Athens, Greece, 11527
      • Laiko General Hospital | Athina, Greece, 115 26
      • University Hospital of Ioannina | Ioannina, Greece, 455 00
      • Ippokrateio General Hospital | Thessaloníki, Greece, 546 42
      • Ospedale "A. Perrino" - Brindisi | Brindisi, Italy, 72100
      • Ospedale Pediatrico Microcitemico | Cagliari, Italy, 09121
      • Ospedale Sant'Anna | Ferrara, Italy, 44124
      • Ente Ospedaliero Ospedali Galliera | Genova, Italy, 16128
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milano, Italy, 20122
      • A.O.U Di Modena | Modena, Italy, 41124
      • AOU L. Vanvitelli Universita degli Studi della Campania Luigi Vanvitelli | Napoli, Italy, 80138
      • A.O.U. San Luigi Gonzaga | Orbassano, Italy, 10043
      • Chronic Care Center | Beyrouth, Lebanon, 9999
      • Hospital Sultanah Aminah Johor Bahru | Johor Bahru, Malaysia, 80100
      • Hospital Queen Elizabeth, Kota Kinabalu | Kota Kinabalu, Malaysia, 88586
      • Hospital Sultanah Bahiyah | Kota Setar, Malaysia, 05460
      • Hospital Tunku Azizah | Kuala Lumpur, Malaysia, 50300
      • Hospital Tengku Ampuan Afzan | Kuantan, Malaysia, 25100
      • Hospital Umum Sarawak | Kuching, Malaysia, 93586
      • Hospital Ampang | Pandan Indah, Malaysia, 68000
      • Hospital Pulau Pinang | Pulau Pinang, Malaysia, 10990
      • Amsterdam Universitair Medisch Centrum, Locatie AMC | Amsterdam, Netherlands, 1105 AZ
      • Universitair Medisch Centrum Utrecht | Utrecht, Netherlands, 3584 CX
      • Erasmus MC | Westzeedijk 353, Netherlands, 3015 AA
      • King Abdulaziz Hospital - Al Ahsa | Al-Ahsa, Saudi Arabia, 31982
      • King Abdullah International Medical Research Center | Riyadh, Saudi Arabia, 14611
      • King Khalid University Hospital | Riyadh, Saudi Arabia, 90210
      • Hospital Universitario Vall d'Hebron | Barcelona, Spain, 08035
      • Hospital Universitario La Paz | Madrid, Spain, 28046
      • Hospital Universitario Virgen Arrixaca | Murcia, Spain, 30120
      • Hospital Universitario Virgen del Rocío | Sevilla, Spain, 41013
      • Changhua Christian Hospital | Changhua, Taiwan, 500
      • National Taiwan University Hospital | Taipei, Taiwan, 100
      • Phramongkutklao Hospital | Bangkok, Thailand, 10400
      • Ramathibodi Hospital | Bangkok, Thailand, 10400
      • Faculty of Medicine Siriraj Hospital | Bangkok, Thailand, 10700
      • Maharaj Nakorn Chiang Mai Hospital | Chiang Mai, Thailand, 50200
      • Srinagarind Hospital, Khon Kaen University | Mueang Khon Kaen, Thailand, 40000
      • Naresuan University Hospital | Mueang Phitsanulok, Thailand, 65000
      • King Chulalongkorn Memorial Hospital | Pathum Wan, Thailand,
      • Acibadem Adana Hospital | Adana, Turkey, 1130
      • Akdeniz University Faculty of Medicine | Antalya, Turkey, 07059
      • Çukurova University | Balcali, Turkey, 01330
      • Ege University Faculty of Medicine | Bornova, Turkey, 35040
      • Istanbul University Faculty of Medicine | Fatih, Turkey, 34093
      • Hacettepe University | Mersin, Turkey,
      • Burjeel Medical City | Abu Dhabi, United Arab Emirates,
      • Imperial College Healthcare NHS Trust - Hammersmith Hospital | London, United Kingdom, W12 0HS
      • University College London | London, United Kingdom, WC1E 6BT
      Investigators

        More Information

        Additional Relevant MeSH Terms

        • Thalassemia
        • beta-Thalassemia
        • alpha-Thalassemia
        • Anemia, Hemolytic, Congenital
        • Anemia, Hemolytic
        • Anemia
        • Hematologic Diseases
        • Hemoglobinopathies
        • Genetic Diseases, Inborn