NCT04770753进行中（未招募）3 期
A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 194
- 试验地点
- 103
- 主要终点
- Double-Blind Period: Percentage of Participants Who Achieved Hemoglobin (Hb) Response From Week 12 Through Week 24 Compared With Baseline
研究概览
简要总结
The primary purpose of this study was to compare the effect of mitapivat versus placebo on hemolytic anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT).
详细描述
The mitapivat group included 130 participants whereas the placebo group had 64 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Hb electrophoresis, Hb high-performance liquid chromatography (HPLC)), and/or deoxyribonucleic acid (DNA) analysis;
- •Hb concentration ≤10.0 grams per deciliter (g/dL) (100.0 grams per liter [g/L]), based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period;
- •Non-transfusion-dependent, defined as ≤5 red blood cell (RBC) units during the 24-week period before randomization; and no RBC transfusions ≤8 weeks before providing informed consent and no RBC transfusions during the Screening Period;
- •If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization;
- •Women of child-bearing potential (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, 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.
排除标准
- •Pregnant, breastfeeding, or parturient
- •Documented history of homozygous or heterozygous sickle hemoglobin (HbS) or hemoglobin C (HbC);
- •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 ≥18 weeks before randomization;
- •Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization;
- •History of malignancy, (active or treated) ≤5 years before providing informed consent;
- •History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;
- •Hepatobiliary disorders;
- •Estimated glomerular filtration rate <45 milliliters per minute (mL/min)/1.73 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) ≤16 weeks 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 ≥10 weeks before randomization;
- •Known allergy 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)
研究组 & 干预措施
Mitapivat
Experimental
Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind (DB) period and for up to 5 years in open label extension (OLE) period.
干预措施: Mitapivat (Drug)
Placebo
Placebo Comparator
Placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period.
干预措施: Mitapivat (Drug)
Placebo
Placebo Comparator
Placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period.
干预措施: Placebo Matching Mitapivat (Drug)
结局指标
主要结局
Double-Blind Period: Percentage of Participants Who Achieved Hemoglobin (Hb) Response From Week 12 Through Week 24 Compared With Baseline
时间窗: Double-Blind Period: Baseline up to Week 12 through Week 24
Hb response is defined as ≥10 grams/ liter (g/L) (1.0 gram per deciliter) (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline. Hb response was tested using the Mantel-Haenszel stratum weighted method adjusting for randomization stratification factors. Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed.
次要结局
- Double-Blind Period: Change From Baseline in Average Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue Subscale Score From Week 12 Through Week 24(Double-Blind Period: Baseline, Week 12 through Week 24)
- Double-Blind Period: Change From Baseline in Average Hb Concentration From Week 12 Through Week 24(Double-Blind Period: Baseline, Week 12 through Week 24)
- Double-Blind Period: Percentage of Participants Who Achieved Hb 1.5+ Response From Week 12 Through Week 24 Compared With Baseline(Double-Blind Period: Baseline up to Week 12 through Week 24)
- Double-Blind Period: Change From Baseline in Indirect Bilirubin at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Haptoglobin at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Reticulocytes at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Erythropoietin at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Percentage of Participants Who Achieved Patient Global Impression of Severity (PGIS)- Fatigue Response at Weeks 12, 16, 20, and 24(Double-Blind Period: At Weeks 12, 16, 20, and 24)
- Double-Blind Period: Percentage of Participants Who Achieved the Patient Global Impression of Change (PGIC)- Fatigue Response at Weeks 12, 16, 20, and 24(Double-Blind Period: At Weeks 12, 16, 20, and 24)
- Double-Blind Period: Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Serum Ferritin at Week 24(Double-Blind Period: Baseline, Week 24)
- Double-Blind Period: Change From Baseline in Transferrin Saturation (TSAT) at Week 24(Double-Blind Period: Baseline, Week 24)
- 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(Double-Blind Period: From the time of signing informed consent to Week 24)
- Double-Blind Period: Plasma Concentration of Mitapivat(Double-Blind Period: Pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of Mitapivat(Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Time of Last Quantifiable Concentration (Tlast) of Mitapivat(Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Maximum Observed Plasma Concentration (Cmax) of Mitapivat(Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat(Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Last Quantifiable Plasma Concentration (Clast) of Mitapivat(Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Blood Concentration of Adenosine Triphosphate (ATP)(Double-Blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Double-Blind Period: Blood Concentration of 2,3 - Diphosphoglycerate (2,3-DPG)(Double-Blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20)
- Open-Label Extension Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity of Greater Than or Equal to Grade 3(Open-Label Extension Period: From week 24 up to end of study (approximately 5 years))
研究者
研究点 (103)
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