2025-524706-15-00招募中3 期
A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy, Pharmacokinetics, and Safety of Mitapivat in Pediatric Subjects With α- or β-Non–Transfusion-Dependent Thalassemia (ENERGIZEKids)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Hb response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline
研究概览
简要总结
To compare the effect of mitapivat versus placebo on anemia in subjects with α- or β-non–transfusion-dependent thalassemia
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Written informed consent/assent from the subject (or their legally authorized representative, parent(s), or legal guardian) must be obtained before any study-related procedures are conducted, and subjects must be willing to comply with all study procedures for the duration of the study.
- •Aged 1 to <18 years and weighing at least 7 kg at the time of providing informed consent/assent.
- •Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, HbE/β-thalassemia, or α-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 α- and β-globin genotyping performed by the study central laboratory can be used.
- •Hb concentration ≤10.0 g/dL (100.0 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 transfusion episodes (also referred to as “transfusion events”) during the 24-week period before randomization and no RBC transfusions ≤8 weeks before providing informed consent/assent and no RBC transfusions during the Screening Period.
- •If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization.
- •Female subjects who have attained menarche must be abstinent of sexual activities that may induce 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 informed consent/assent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can include an acceptable barrier method
排除标准
- •Pregnant or breastfeeding.
- •Renal dysfunction as defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2
- •Nonfasting triglycerides >215 mg/dL (5 mmol/L).
- •Active infection requiring systemic antimicrobial therapy at the time of providing informed consent/assent. 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.
- •Subjects with known active hepatitis B or hepatitis C virus infection.
- •Subjects with known HIV infection.
- •History of major surgery (including splenectomy) ≤16 weeks before providing informed consent/assent and/or a major surgical procedure planned during the study.
- •Current enrollment or past participation (within ≤12 weeks or a timeframe equivalent to 5 half-lives of the investigational study drug before administration of the first dose of 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 CYP3A4/5 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, magnesium stearate, and the Opadry filmcoat [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD&C Blue #2]).
- •Documented history of homozygous or heterozygous HbS or HbC.
- •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: • Subjects who are institutionalized by regulatory or court order • Subjects 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)
- •Prior exposure to gene therapy or prior bone marrow or stem cell transplantation, including any prior exposure to myeloablative chemotherapy.
- •Any conditions other than thalassemia expected to affect sexual maturation.
- •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/assent, 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 or clinically relevant QT prolongation within 6 months before providing informed consent/assent.
- •Hepatobiliary disorders, including but not limited to: a. Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis b. Clinically symptomatic cholelithiasis or cholecystitis (prior cholecystectomy is not exclusionary) c. History of drug-induced cholestatic hepatitis d. Aspartate aminotransferase >2.5×ULN (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase >2.5×ULN (unless due to hepatic iron deposition)
研究组 & 干预措施
Placebo matching Mitapivat, Placebo matching Mitapivat
Placebo
干预措施: Placebo matching Mitapivat (Drug)
MITAPIVAT, MITAPIVAT
Test
干预措施: MITAPIVAT (Drug)
结局指标
主要结局
Hb response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline
Hb response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline
次要结局
- 1.Change from baseline in average Hb concentration from Week 12 through Week 24
- 2. 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
- 3. Change from baseline in indirect bilirubin, lactate dehydrogenase, and haptoglobin at Week 24
- 4. Change from baseline in reticulocytes and erythropoietin at Week 24
- 5. Changes from baseline in sex hormones, sexual maturity rating with Tanner stage, and ovarian cysts (female subjects only) through Week 24 for patients in Cohort 1
- 6. Changes over time in height-for-age z-score, weight-for-age z-score, and body mass index-for-age z-score
- 7. Changes from baseline in bone mineral density through Week 24
- 8. Type, severity, and relationship of AEs and SAEs
- 9. Change from baseline through Week 24 on patient reported fatigue and other symptoms of thalassemia to assess the impact of these symptoms on HRQOL including physical and school function as measured by the PedsQL Multidimensional Fatigue Scale and PedsQL 4.0 Generic Core Scales
- 10. Change from baseline in markers of iron metabolism (serum iron, total iron-binding capacity, transferrin, transferrin saturation) and indicators of iron overload (serum ferritin) at Week 24
- 11. Plasma concentrations and pharmacokinetic parameters of mitapivat at Week 4.
研究者
Scientific Communications
Scientific
Agios Pharmaceuticals Inc.
研究点 (2)
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