A Phase 2, Open-label, Multicenter Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Subjects With Non-transfusion-dependent Thalassemia

Agios Pharmaceuticals, Inc.7 个研究点分布在 3 个国家目标入组 20 人2019年3月20日

适应症Thalassemia

干预措施AG-348

概览

阶段: 2 期
干预措施: AG-348
疾病 / 适应症: Thalassemia
发起方: Agios Pharmaceuticals, Inc.
入组人数: 20
试验地点: 7
主要终点: Percentage of Participants Achieving a Hemoglobin Response (HR)
状态: 进行中（未招募）
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

Study AG348-C-010 is a multicenter study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of treatment with AG-348 in adult participants with non-transfusion-dependent thalassemia (NTDT). This study includes a core period (up to 24 weeks) followed by an extension period (up to 10 years) for eligible participants. 20 participants with NTDT were enrolled. The initial dose of AG-348 was 50 milligrams (mg) twice daily (BID) with one potential dose-level increase to 100 mg BID at the Week 6 visit based on the participant's safety and hemoglobin (Hb) concentrations.

注册库

clinicaltrials.gov

开始日期

2019年3月20日

结束日期

2030年9月30日

最后更新

上个月

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

Agios Pharmaceuticals, Inc.

责任方

Sponsor

入排标准

入选标准

•Informed consent;
•Known medical history of thalassemia, including β-thalassemia intermedia, Hb E β-thalassemia, α-thalassemia (Hb H disease), or β-thalassemia with mutations of 1 or more α genes;
•Documented clinical laboratory confirmation of thalassemia by Hb electrophoresis/high-performance liquid chromatography (HPLC) or deoxyribonucleic acid (DNA) analysis, either from medical records or during the screening period;
•Hb concentration ≤10.0 grams per deciliter (g/dL), regardless of sex, based on an average of at least 2 Hb measurements (separated by a minimum of 7 days) during the screening period;
•Considered non-transfusion-dependent, defined as having no more than 5 units of red blood cells (RBCs) transfused during the 24-week period up to the first day of study drug and no RBC transfusions in the 8 weeks prior to the first day of study drug;
•Adequate organ function;
•For women of reproductive potential: negative serum pregnancy test during the screening period and a negative serum or urine pregnancy test on Day 1;
•For women of reproductive potential as well as men with partners who are women of reproductive potential: be abstinent as part of their usual lifestyle, or agreement to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men;
•Willingness to comply with all study procedures for the duration of the study;

排除标准

•Known history of diagnosis of Hb S or Hb C forms of thalassemia;
•Significant medical condition that confers an unacceptable risk to participating in the study, and/or could confound the interpretation of the study data;
•Splenectomy scheduled during the study treatment period or having undergone splenectomy within 12 months prior to signing informed consent;
•Currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo;
•Exposure to any investigational drug, device, or procedure within 3 months prior to the first day of study drug;
•Prior exposure to sotatercept (ACE-011), luspatercept (ACE-536), ruxolitinib, or gene therapy;
•Prior bone marrow or stem cell transplant;
•Currently pregnant or breastfeeding;
•History of major surgery within 6 months of signing informed consent;
•Currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first day of study drug;

研究组 & 干预措施

AG-348

Participants with alpha or beta thalassemia received AG-348 50 mg twice daily (BID), orally up to Week 6. Following Week 6, depending on the participants' safety and hemoglobin (Hb) concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.

干预措施: AG-348

结局指标

主要结局

Percentage of Participants Achieving a Hemoglobin Response (HR)

时间窗: Up to 12 weeks

HR was defined as a ≥1.0 gram per deciliter (g/dL) increase in Hb concentration from Baseline at 1 or more assessments between Week 4 and Week 12 (inclusive). A participant's Baseline Hb concentration was defined as the average of all the participant's available Hb concentrations during the screening period up to the first dose of study drug.

次要结局

Average Change From Baseline in Hb Concentrations From Week 12 to Week 24(Baseline, Week 12 to Week 24)
Percentage of Participants Achieving a Sustained Hb Response (sHR)(Week 12 to Week 24)
Percentage of Participants Achieving a Delayed Hb Response(Week 12 to Week 24)
Change From Baseline in Bilirubin(Up to approximately 10.5 years)
Change From Baseline in Lactate Dehydrogenase (LDH)(Up to approximately 10.5 years)
Change From Baseline in Haptoglobin(Up to approximately 10.5 years)
Change From Baseline in Hb Concentration Over the Duration of the Extension Period(Baseline up to approximately 10.5 years)
Time to First ≥1.0 g/dL Increase in Hb Concentration(Up to Week 24)
Change From Baseline in Reticulocyte Count(Up to approximately 10.5 years)
Change From Baseline in Nucleated Red Blood Cells (NRBCs)(Up to approximately 10.5 years)
Change From Baseline in Erythropoietin (EPO)(Up to approximately 10.5 years)
Change From Baseline in Soluble Transferrin Receptor(Up to approximately 10.5 years)
Drug Concentrations Over Time for AG-348(Predose (60 minutes) and 0.00 hour, 0.50 hour, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
AUC0-8h: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours of AG-348(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of AG-348(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
Ctrough: Observed Plasma Concentration at the End of a Dosing Interval of AG-348(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
Cmax: Maximum Observed Plasma Concentration of AG-348(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
Tlast: Time of the Last Quantifiable Concentration of AG-348(Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation(From signing the inform consent form up to data cut-off date: 20 August 2020 (Up to approximately 19 months))