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一项评估 Mitapivat 在输血依赖性α-或β-地中海贫血（α-或β-TDT）参与者中的疗效和安全性的研究 (ENERGIZE-T)

2026年10月27日 更新者：Agios Pharmaceuticals, Inc.

一项 3 期、双盲、随机、安慰剂对照、多中心研究，评估 Mitapivat 在输血依赖性 α 或 β 地中海贫血患者中的疗效和安全性 (ENERGIZE-T)

The primary objective of this study was to compare the effect of mitapivat versus placebo on transfusion burden in participants with α- or β-transfusion-dependent thalassemia.

研究概览

地位

主动，不招人

条件

干预/治疗

详细说明

The mitapivat group included 171 participants. The placebo group included 87 participants.

研究类型

介入性

注册 (实际的)

258

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 丹麦
      • Hovedstaden、丹麦、2100
        • Rigshospitalet
  • 保加利亚
      • Kyustendil、保加利亚、2500
        • MHAT "Dr. Nikola Vasiliev" AD
      • Pleven、保加利亚、5800
        • UMHAT "Dr. Georgi Stranski" Pleven
      • Plovdiv、保加利亚、4002
        • UMHAT "Sveti Georgi" EAD
      • Sofia、保加利亚、1756
        • SHATHD Sofia
      • Stara Zagora、保加利亚、6000
        • UMHAT "Prof. Dr. Stoyan Kirkovich"
  • 加拿大
    • Alberta
      • Calgary、Alberta、加拿大、T2N 2T9
        • Foothills Medical Centre
    • Ontario
      • Toronto、Ontario、加拿大、M5G 2C4
        • Toronto General Hospital, University Health Network
  • 台湾
      • Taipei、台湾、100
        • National Taiwan University Hospital
  • 土耳其（türkiye）
      • Adana、土耳其（türkiye）、1130
        • Acibadem Adana Hospital
      • Antalya、土耳其（türkiye）、07059
        • Akdeniz University Faculty of Medicine
      • Balcalı、土耳其（türkiye）、01330
        • Çukurova University
      • Bornova、土耳其（türkiye）、35040
        • Ege University Faculty of Medicine
      • Fatih、土耳其（türkiye）、34093
        • Istanbul University Faculty of Medicine
      • Mersin、土耳其（türkiye）
        • Hacettepe University
  • 巴西
      • Ribeirão Preto、巴西、14051-260
        • Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
      • São Paulo、巴西、04006-002
        • GSH Banco de Sangue de São Paulo
  • 希腊
      • Achaia、希腊、26504
        • University General Hospital of Patras
      • Athens、希腊、11527
        • Children's Hospital Agia Sophia, National and Kapodistrian University of Athens Medical School
      • Athens、希腊、115 26
        • Laiko General Hospital
      • Ioannina、希腊、455 00
        • University Hospital of Ioannina
      • Thessaloniki、希腊、546 42
        • Ippokrateio General Hospital
  • 德国
      • Berlin、德国、13353
        • Charité - UB - CVK - Medizinische Klinik
      • Essen、德国、45122
        • Universitätsklinikum Essen
      • Leipzig、德国、04103
        • Universitätsklinikum Leipzig
  • 意大利
      • Brindisi、意大利、72100
        • Ospedale "A. Perrino" - Brindisi
      • Cagliari、意大利、09121
        • Ospedale Pediatrico Microcitemico
      • Ferrara、意大利、44124
        • Ospedale Sant'Anna
      • Genova、意大利、16128
        • Ente Ospedaliero Ospedali Galliera
      • Milan、意大利、20122
        • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
      • Modena、意大利、41124
        • A.O.U Di Modena
      • Naples、意大利、80138
        • AOU L. Vanvitelli Universita degli Studi della Campania Luigi Vanvitelli
      • Orbassano、意大利、10043
        • A.O.U. San Luigi Gonzaga
  • 沙特阿拉伯
      • Riyadh、沙特阿拉伯、14611
        • King Abdullah International Medical Research Center
      • Riyadh、沙特阿拉伯、90210
        • King Khalid University Hospital
  • 法国
      • Créteil、法国、94010
        • CHU Hôpital Henri Mondor
      • Lyon、法国、69003
        • Hôpital Edouard Herriot, CHU de Lyon
      • Marseille、法国、13385
        • CHU Hôpital de la Timone
      • Paris、法国、75015
        • Hôpital Necker Enfants Malades
  • 泰国
      • Bangkok、泰国、10400
        • Phramongkutklao Hospital
      • Bangkok、泰国、10400
        • Ramathibodi Hospital
      • Bangkok、泰国、10700
        • Faculty of Medicine Siriraj Hospital
      • Chiang Mai、泰国、50200
        • Maharaj Nakorn Chiang Mai Hospital
      • Khon Kaen、泰国、40000
        • Srinagarind Hospital, Khon Kaen University
      • Mueang Phitsanulok、泰国、65000
        • Naresuan University Hospital
      • Pathum Wan、泰国
        • King Chulalongkorn Memorial Hospital
  • 美国
    • Arizona
      • Phoenix、Arizona、美国、85016-7710
        • Phoenix Children's Hospital
    • California
      • La Jolla、California、美国、92093
        • San Diego Hospital, UC San Diego Health
      • Oakland、California、美国、94609-1809
        • Children's Hospital Oakland
      • Palo Alto、California、美国、94304-1601
        • Stanford Medicine
    • Massachusetts
      • Boston、Massachusetts、美国、02115
        • Boston Children's Hospital
    • Michigan
      • Detroit、Michigan、美国、48201-2196
        • Children's Hospital of Michigan
    • New York
      • New York、New York、美国、10065-4870
        • Weill Cornell Medical Center
    • North Carolina
      • Durham、North Carolina、美国、27710-3038
        • Duke University Medical Center
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19104
        • Penn Medicine - University of Pennsylvania Health System
    • Washington
      • Seattle、Washington、美国、98101
        • Seattle Cancer Care Alliance, University of Washington
  • 英国
      • London、英国、WC1E 6BT
        • University College London
      • London、英国、W12 0HS
        • Imperial College Healthcare NHS Trust - Hammersmith Hospital
  • 荷兰
      • Amsterdam、荷兰、1105 AZ
        • Amsterdam Universitair Medisch Centrum, Locatie AMC
      • Utrecht、荷兰、3584 CX
        • Universitair Medisch Centrum Utrecht
      • Westzeedijk 353、荷兰、3015 AA
        • Erasmus MC
  • 西班牙
      • Barcelona、西班牙、08035
        • Hospital Universitario Vall d'Hebron
      • Madrid、西班牙、28046
        • Hospital Universitario La Paz
      • Murcia、西班牙、30120
        • Hospital Universitario Virgen Arrixaca
      • Seville、西班牙、41013
        • Hospital Universitario Virgen del Rocío
  • 阿拉伯联合酋长国
      • Abu Dhabi、阿拉伯联合酋长国
        • Burjeel Medical City
  • 马来西亚
      • Alor Star、马来西亚、05460
        • Hospital Sultanah Bahiyah
      • Johor Bahru、马来西亚、80100
        • Hospital Sultanah Aminah Johor Bahru
      • Kota Kinabalu、马来西亚、88586
        • Hospital Queen Elizabeth, Kota Kinabalu
      • Kuala Lumpur、马来西亚、50300
        • Hospital Tunku Azizah
      • Kuantan、马来西亚、25100
        • Hospital Tengku Ampuan Afzan
      • Kuching、马来西亚、93586
        • Hospital Umum Sarawak
      • Pandan Indah、马来西亚、68000
        • Hospital Ampang
      • Pulau Pinang、马来西亚、10990
        • Hospital Pulau Pinang
  • 黎巴嫩
      • Beirut、黎巴嫩、9999
        • Chronic Care Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Greater than or equal to (≥)18 years of age at the time of providing informed consent;
  • 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 red blood cells (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 Federal Food, Drug, and Cosmetic (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).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：Mitapivat

Participants randomized to receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 48 weeks in the double-blind (DB) period and for up to 5 years in the open label extension (OLE) period.
药品：Mitapivat

Tablets

其他名称：
  • AG-348
  • AG-348硫酸盐水合物
  • 硫酸米匹伐特
安慰剂比较：Placebo

Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the DB period followed by mitapivat 100 mg, orally, BID for up to 5 years in the OLE period.
药品：Mitapivat

Tablets

其他名称：
  • AG-348
  • AG-348硫酸盐水合物
  • 硫酸米匹伐特
药品：Placebo Matching Mitapivat

Tablets

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Double-blind Period: Percentage of Participants Who Achieved Transfusion Reduction Response (TRR)
大体时间：Double-blind Period: Baseline through 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 transfusion burden standardized to 12 weeks. Baseline transfusion burden standardized to 12 weeks= (12/24) × total number of RBC units transfused during 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 12 (Day 85) were considered nonresponders.
Double-blind Period: Baseline through Week 48

次要结果测量

结果测量
措施说明
大体时间
双盲期：Mitapivat的血浆浓度
大体时间：双盲期：第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
双盲期：第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
双盲周期：Mitapivat的最大观察到的血浆浓度（CMAX）
大体时间：双盲期：剂量前剂量，剂量后第36周7小时
双盲期：剂量前剂量，剂量后第36周7小时
双盲周期：达到Mitapivat的最大观察到的血浆浓度（TMAX）的时间
大体时间：双盲期：剂量前剂量，剂量后第36周7小时
双盲期：剂量前剂量，剂量后第36周7小时
双盲期：Mitapivat的最后可量化浓度（TLAST）的时间
大体时间：双盲期：剂量前剂量，剂量后第36周7小时
双盲期：剂量前剂量，剂量后第36周7小时
双盲时期：三磷酸腺苷的血液浓度（ATP）
大体时间：双盲期：第1天预剂量；第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
双盲期：第1天预剂量；第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
双盲期：2,3-二磷酸甘油酸的血液浓度（2,3-DPG）
大体时间：双盲期：第1天预剂量；第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
双盲期：第1天预剂量；第12周预剂量；在第24周预剂量；前剂量，0.5、1、3、5、7小时在第36周剂量
Double-blind Period: Percentage of Participants Who Achieved TRR2
大体时间：Double-blind period: Baseline through Week 48

TRR2, defined as a ≥50% reduction in transfused RBC units in any consecutive 24-week period through Week 48 compared with the 24-week baseline transfusion burden, is reported. Baseline transfusion burden standardized to 24 weeks is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 24 (Day 169) were considered nonresponders.
Double-blind period: Baseline through Week 48
Double-blind Period: Percentage of Participants Who Achieved TRR3
大体时间：Double-blind period: Baseline up to Week 13 through Week 48

TRR3, defined as a ≥33% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks= (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders.
Double-blind period: Baseline up to Week 13 through Week 48
Double-blind Period: Percentage of Participants Who Achieved TRR4
大体时间：Double-blind period: Baseline up to Week 13 through Week 48

TRR4, defined as a ≥50% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks = (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders.
Double-blind period: Baseline up to Week 13 through Week 48
Double-blind Period: Percent Change From Baseline in Transfused RBC Units
大体时间：Double-blind Period: Baseline, Week 13 through Week 48

Transfusion burden from Week 13 through Week 48 standardized to 36 weeks is defined as number of transfused RBC units from Day 85 through Week 48 in the Double-blind Period ×36/(Number of days from Day 85 through Week 48 in the Double-blind Period/7). Baseline transfusion burden standardized to 36 weeks= (36/24)× is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or within 168 days before the start of study treatment for participants randomized and dosed.
Double-blind Period: Baseline, Week 13 through Week 48
Double-blind Period: Percentage of Participants Who Achieved Transfusion-Independence
大体时间：Double-blind Period: Baseline through Week 48

Transfusion-independence is defined as transfusion-free for ≥8 consecutive weeks through Week 48 in the double-blind period.
Double-blind Period: Baseline through Week 48
Double-blind Period: Change From Baseline in Iron Levels
大体时间：Double-blind Period: Baseline through Week 48

Iron metabolism was assessed based on Iron levels.
Double-blind Period: Baseline through Week 48
Double-blind Period: Change From Baseline in Serum Ferritin Levels
大体时间：Double-blind Period: Baseline through Week 48

Iron metabolism was assessed based on serum ferritin levels.
Double-blind Period: Baseline through Week 48
Double-blind Period: Change From Baseline in Total Iron Binding Capacity
大体时间：Double-blind Period: Baseline through Week 48

Iron metabolism was assessed based on total iron binding capacity.
Double-blind Period: Baseline through Week 48
Double-blind Period: Change From Baseline in Transferrin Saturation (TSAT) Levels
大体时间：Double-blind Period: Baseline through Week 48

Iron metabolism was assessed based on TSAT levels. Transferrin saturation is reported by dividing value of serum iron by total iron binding capacity.
Double-blind Period: Baseline through Week 48
Double-blind Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3
大体时间：Double-blind Period: From first dose of study drug up to week 48

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and includes both serious & non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.
Double-blind Period: From first dose of study drug up to week 48
Open-label Extension Period: Number of Participants With TEAEs, Serious TEAEs, Related TEAEs, Related TEAEs and TEAEs With Severity of Greater Than or Equal to 3
大体时间：Open-Label Extension Period: From Week 48 up to end of study (approximately 5 years)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and includes both serious & non-serious TEAEs. Severity of abnormalities was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE.
Open-Label Extension Period: From Week 48 up to end of study (approximately 5 years)
Double-blind Period: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of Mitapivat
大体时间：Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36

Area under the concentration-time curve from time zero to Tlast on dosing day, calculated using the linear-log trapezoidal rule.
Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36
Double-blind Period: Last Quantifiable Plasma Concentration (Clast) of Mitapivat
大体时间：Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36

Clast is the last quantifiable concentration after a single dose or within the dosing interval (tau) for multiple doses.
Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Agios Pharmaceuticals, Inc.

调查人员

  • 学习椅：Medical Affairs、Agios Pharmaceuticals, Inc.

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2021年11月30日

初级完成 (实际的)

2024年4月11日

研究完成 (估计的)

2029年6月1日

研究注册日期

首次提交

2021年2月18日

首先提交符合 QC 标准的

2021年2月22日

首次发布 (实际的)

2021年2月25日

研究记录更新

最后更新发布 (实际的)

2026年10月28日

上次提交的符合 QC 标准的更新

2026年10月27日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • AG348-C-018
  • 2021-000212-34 (EudraCT编号)
  • 2024-512747-23-00 (克蒂斯)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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