Cardiomyopathy, Secondary, Friedreich Ataxia
Conditions
Keywords
Friedreich Ataxia Cardiomyopathy, FA-CM, Friedreich Ataxia, Friedreich's Ataxia, FA, FRDA, Cardiomyopathy, Genetic Cardiomyopathy, Mitochondrial Cardiomyopathy, Cardiac Disease, Left Ventricular Hypertrophy, Hypertrophic Cardiomyopathy (Non-Obstructive), HCM, Gene Therapy, FXN Gene, FXN, Frataxin Gene, LX2006, SUNRISE-FA 2, SUNRISE-FA, CLARITY
Brief summary
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).
Interventions
GENETICLX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
OTHERUsual 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).
Sponsors
Lexeo Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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).
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 2: Change in clinical routine safety laboratory tests as assessed by standardized clinical laboratory reference ranges | Through Month 60 |
| Cohort 2: Change in clinical vital signs (body temperature [°C]) | Through Month 60 |
| Cohort 2: Change in clinical vital signs (systolic and diastolic blood pressure [mmHg]) | Through Month 60 |
| Cohort 1: Percent change from baseline in left ventricular mass index by cardiac MRI | At Week 26 |
| Cohort 2: Change in clinical vital signs (oxygen saturation [%]) | 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]) | Through Month 60 |
| Cohort 2: Change in clinical vital signs (heart rate [beats per minute]) | Through Month 60 |
| Cohort 2: Change in clinical vital signs (respiratory rate [breaths per minute]) | Through Month 60 |
| Cohort 2: Incidence and severity of treatment-emergent adverse events | Through Month 60 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 \[milliseconds\] |
| 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 | — |
| 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 | * Death due to any cause * Hospitalization for heart failure * Non-fatal stroke * Non-fatal heart attack * Non-fatal life-threatening rapid or irregular heartbeat * Heart transplant * Insertion of a left ventricular assist device (pump) in the heart |
| Cohort 1: Change from baseline in modified Friedreich's Ataxia Rating Scale | At Week 26, at Week 52, and through Month 60 | A neurological assessment tool for Friedreich ataxia that is measured on a scale of 0 to 93 with high scores indicating greater physical impairment |
| Cohort 1: Change from baseline in Kansas City Cardiomyopathy Questionnaire | At Week 26, at Week 52, and through Month 60 | A cardiac assessment tool scored from 0 to 100, with higher scores indicating better health status and lower scores reflecting more severe heart failure symptoms and functional limitations |
| 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 | — |
Countries
United States
Contacts
CONTACTLexeo Clinical Trials
STUDY_DIRECTORLexeo Clinical Trials
Lexeo Therapeutics, Inc.
Outcome results
None listed