2024-515025-28-00招募中3 期
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Subjects With Pyruvate Kinase Deficiency Who Are Not Regularly Transfused, Followed by a 5-Year Open-label Extension Period
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 14
- 试验地点
- 7
- 主要终点
- Hb response, defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 12, 16, and 20 during the Double-blind Period. The individual subject’s baseline Hb concentration is defined as the average of all available Hb concentrations collected for that subject during the Screening Period up to the first dose of study drug
研究概览
简要总结
To determine the efficacy of treatment with mitapivat compared with placebo, as assessed by the increase in hemoglobin (Hb) concentrations in pediatric subjects with pyruvate kinase deficiency (PK deficiency) who are not regularly transfused.
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Written informed consent from the subject, or the subject’s legally authorized representative, parent(s), or legal guardian, and the subject’s assent, where applicable (informed consent/assent) 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. Subjects between 12 and 24 months of age must weigh a minimum of 7 kg.
- •Clinical laboratory confirmation of PK deficiency, defined as documented presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation, as determined per the genotyping performed by the study central genotyping laboratory
- •No more than 5 red blood cell (RBC) transfusions in the 52-week period before providing informed consent/assent and no RBC transfusions ≤12 weeks before administration of the first dose of study drug
- •Hemoglobin concentration ≤10 g/dL for subjects 12 to <18 years of age or ≤9 g/dL for subjects 1 to <12 years of age during the Screening Period. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
- •Receiving folic acid supplementation as part of routine clinical care for at least 21 days before administration of the first dose of study drug, to be continued during study participation
- •Female subjects who have attained menarche and/or breast development in Tanner Stage 2 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 (including the time required to dose taper). The second form of contraception can include an acceptable barrier method.
排除标准
- •Pregnant or breastfeeding
- •Subjects with known HIV infection
- •History of major surgery (including splenectomy) ≤6 months before providing informed consent/assent and/or planning on undergoing a major surgical procedure during the Screening or Double-blind Period
- •Current enrollment or past participation (within 90 days before the first dose of study drug or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational study drug or device
- •Prior exposure to gene therapy, or bone marrow or stem cell transplantation
- •Currently receiving hematopoietic stimulating agents; the last dose must have been administered at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before randomization
- •Receiving products that are strong inhibitors of cytochrome P450 (CYP)3A4/5 that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of CYP3A4 that have not been stopped for ≥28 days or a time frame equivalent to 5 half-lives (whichever is longer), before randomization
- •Receiving anabolic steroids, including testosterone preparations that have not been stopped for at least 28 days before randomization
- •Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD&C Blue #2], Opadry® II White [hypromellose, titanium dioxide, lactose monohydrate, and triacetin], and magnesium stearate)
- •Any medical, hematologic, 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 included 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)
- •Receiving a pyruvate kinase activator that has not been stopped for ≥52 weeks before providing informed consent/assent
- •Homozygous for the R479H mutation or have 2 nonmissense mutations, without the presence of another missense mutation, in the PKLR gene as determined per the genotyping performed by the study central genotyping laboratory
- •History of malignancy
- •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 of cirrhosis or severe fibrosis b. Clinically symptomatic cholelithiasis or cholecystitis (subjects with prior cholecystectomy are eligible) c. History of drug-induced cholestatic hepatitis d. Aspartate aminotransferase >2.5× the upper limit of normal (ULN) (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase >2.5×ULN (unless due to hepatic iron deposition)
- •Renal dysfunction as defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 (bedside Schwartz equation)
- •Nonfasting triglycerides >440 mg/dL (5 mmol/L)
- •Active uncontrolled infection requiring systemic antimicrobial therapy
- •Subjects with known active hepatitis B or hepatitis C virus infection
结局指标
主要结局
Hb response, defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 12, 16, and 20 during the Double-blind Period. The individual subject’s baseline Hb concentration is defined as the average of all available Hb concentrations collected for that subject during the Screening Period up to the first dose of study drug
Hb response, defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 12, 16, and 20 during the Double-blind Period. The individual subject’s baseline Hb concentration is defined as the average of all available Hb concentrations collected for that subject during the Screening Period up to the first dose of study drug
次要结局
未报告次要终点
研究者
Joshua Pham
Scientific
Agios Pharmaceuticals Inc.
研究点 (7)
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