A Phase 2, Multicenter, Open-label, Randomized, Controlled Study of LX2006 Gene Therapy in Participants With Friedreich Ataxia Cardiomyopathy (SUNRISE-FA 2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Percent change from baseline in left ventricular mass index by cardiac MRI
研究概览
简要总结
The purpose of Study LX2006-03, a multicenter, Phase 2, open-label, randomized, controlled study, is to evaluate the efficacy and safety of LX2006 gene therapy in participants with Friedreich ataxia (FA) cardiomyopathy (CM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Clinical outcomes of interest will be read with blinded assessors using standardized procedures. All post-baseline centrally read imaging and cardiac biomarker high-sensitivity troponin I will be blinded to the investigator, sponsor, and the reader (and the participant).
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age at least 6 years at the time of signing the informed consent (and assent, if applicable).
- •Diagnosis of FA, based on clinical phenotype and genotype (GAA expansion on the frataxin gene)
- •Onset of FA on or before 25 years of age
- •Confirmed left ventricular hypertrophy and abnormal left ventricular mass index
- •Left ventricular ejection fraction at least 30%
- •Anti-AAVrh.10 total antibody titer less than the protocol-specified maximum level
排除标准
- •Presence of other forms of cardiomyopathy that contribute to heart failure
- •Current use of inotrope infusion or presence of a ventricular assist device
- •Contraindication to cardiac MRI
- •Prior organ transplant
- •Previous gene transfer or cell therapy
- •Poorly controlled diabetes (hemoglobin A1c ≥8%)
- •Active hematologic or solid organ cancer
- •Other inclusion/exclusion criteria to be applied as per protocol.
研究组 & 干预措施
Usual Care
Cohort 1: Participants ≥16 years of age with FA-CM Participants will receive usual care for 26 weeks before receiving treatment with LX2006 (single crossover).
干预措施: Usual Care (Other)
LX2006
Cohort 1: Participants ≥16 years of age with FA-CM Cohort 2: Participants ≥6 to <16 years of age with FA-CM. As Cohort 2 will not be randomized, all participants will receive LX2006 upon enrollment. Participants in Cohort 2 will be enrolled after safety is assessed in a group of participants in Cohort 1.
干预措施: LX2006 (Genetic)
结局指标
主要结局
Percent change from baseline in left ventricular mass index by cardiac MRI
时间窗: At Week 26
Cohort 2: Change in clinical vital signs (oxygen saturation [%])
时间窗: Through Month 60
Cohort 2: Change in clinical 12-lead ECG findings (ECG machine automatically calculates the heart rate [beats per minute] and measures PR, QT, QT interval corrected using Fridericia's method intervals, and QRS complex [milliseconds])
时间窗: Through Month 60
Cohort 1: Percent change from baseline in left ventricular mass index by cardiac MRI
时间窗: At Week 26
Cohort 2: Incidence and severity of treatment-emergent adverse events
时间窗: Through Month 60
Cohort 2: Change in clinical routine safety laboratory tests as assessed by standardized clinical laboratory reference ranges
时间窗: Through Month 60
Cohort 2: Change in clinical vital signs (body temperature [°C])
时间窗: Through Month 60
Cohort 2: Change in clinical vital signs (systolic and diastolic blood pressure [mmHg])
时间窗: Through Month 60
Cohort 2: Change in clinical vital signs (heart rate [beats per minute])
时间窗: Through Month 60
Cohort 2: Change in clinical vital signs (respiratory rate [breaths per minute])
时间窗: Through Month 60
次要结局
- Change from baseline in high-sensitivity troponin I(At Week 26 and through Month 60)
- Change from baseline in left ventricular wall thickness and additional imaging outcomes(At Week 26 and through Month 60)
- Incidence and severity of treatment-emergent adverse events(Through Month 60)
- Change in clinical routine safety laboratory tests as assessed by standardized clinical laboratory reference ranges(Through Month 60)
- Change in clinical vital signs (body temperature [°C])(Through Month 60)
- Change in clinical vital signs (systolic and diastolic blood pressure [mmHg])(Through Month 60)
- Change in clinical vital signs (heart rate [beats per minute])(Through Month 60)
- Change in clinical vital signs (respiratory rate [breaths per minute])(Through Month 60)
- Change in clinical vital signs (oxygen saturation [%])(Through Month 60)
- Change from baseline in modified Friedreich's Ataxia Rating Scale(At Week 26 and through Month 60)
- Change from baseline in Kansas City Cardiomyopathy Questionnaire(Through Month 60)
- Healthcare resource use(Through Month 60)
- Cardiovascular events(Through Month 60)
- Patient Global Impressions scales(Through Month 60)
- Change in clinical 12-lead ECG findings(Through Month 60)
- Cohorts 1 and 2: Change from baseline in high-sensitivity troponin I(At Week 26)
- Cohort 1: Change from baseline in maximal wall thickness by cardiac MRI(At Week 26)
- Cohort 1: Number of the following cardiovascular events as collected from the participant by the study doctor during scheduled study visits(At Month 60)
- Cohort 1: Change from baseline in modified Friedreich's Ataxia Rating Scale(At Week 26, at Week 52, and through Month 60)
- Cohort 1: Change from baseline in Kansas City Cardiomyopathy Questionnaire(At Week 26, at Week 52, and through Month 60)
- Cohort 1: Incidence and severity of treatment-emergent adverse events(Through Month 60)
- Cohort 1: Change in clinical routine safety laboratory tests as assessed by standardized clinical laboratory reference ranges(Through Month 60)
- Cohort 1: Change in clinical vital signs (body temperature [°C])(Through Month 60)
- Cohort 1: Change in clinical vital signs (systolic and diastolic blood pressure [mmHg])(Through Month 60)
- Cohort 1: Change in clinical vital signs (heart rate [beats per minute])(Through Month 60)
- Cohort 1: Change in clinical vital signs (respiratory rate [breaths per minute])(Through Month 60)
- Cohort 1: Change in clinical vital signs (oxygen saturation [%])(Through Month 60)
- Cohort 1: Change in clinical 12-lead ECG findings(Through Month 60)
- Cohort 2: Percent change from baseline in left ventricular mass index by cardiac MRI (or by ECHO for participants aged ≥6 to <12 years who did not have the cardiac MRI at baseline)(At Week 26)
- Cohort 2: Change from baseline in maximal wall thickness by cardiac MRI (or by ECHO for participants aged ≥6 to <12 years who did not have the cardiac MRI at baseline)(At Week 26)