A Study of ASP2016 in Adults Who Have Heart Disease Associated With Friedreich Ataxia
NCT Number: NCT06483802
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Friedreich Ataxia|Cardiomyopathy
Interventions: GENETIC: ASP2016|DRUG: Prednisolone
Sponsor: Astellas Gene Therapies
Sex: ALL
Age: ADULT
Enrollment: 14
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-31
Completion Date: 2031-01-31
Locations: University of California - Los Angeles, Los Angeles, California, 90095, United States|University of Florida, Gainesville, Florida, 32608, United States|Boston Children's Hospital, Boston, Massachusetts, 02115, United States|Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229, United States|University of Texas - Houston, Houston, Texas, 77030, United States

Summary:
Friedreich Ataxia is a rare condition that causes damage to the nervous system and muscles. People with Friedreich Ataxia have difficulty walking, lose sensation in their arms and legs, and have slurred speech. It can also affect the heart and many people with Friedrich Ataxia develop serious heart problems. Friedreich Ataxia is a genetic condition which means a faulty gene is passed down through families. This type of gene therapy treats a genetic condition by providing a healthy copy of the gene.

At the time this study started, there was no approved treatment for heart problems in people with Friedreich Ataxia.

In this study, ASP2016 is being tested in humans for the first time. The people taking part are adults with Friedreich Ataxia who have heart problems.

The main aims of the study are to check the safety of ASP2016 and how people cope with (tolerate) ASP2016. ASP2016 is given as a slow injection into a vein. This is called an infusion. People will also take tablets of a medicine called prednisolone. This is taken to stop the immune system interfering with ASP2016.

Each person in the study will be given 1 single infusion of ASP2016. Different small groups will receive lower or higher doses of ASP2016. Each person will stay overnight in the clinic for at least 1 night after their infusion.

For the first few months, people will visit the clinic regularly. There may be the option of home visits by a study nurse at some visits. At the 6-month and 12-month visits extra tests, procedures, and scans will be done. One of these is an ECHO (echocardiogram) scan. This is like an ultrasound scan for the heart. Another is an endomyocardial biopsy. A tiny piece of their heart tissue is removed (biopsy). A flexible hollow tube (catheter) goes into the blood vessels up to the heart. Then, a small device on the end of the catheter takes a tiny piece of heart tissue (about the size of a pencil tip). Another is a cardiac MRI. This takes pictures of the inside of the heart using a powerful magnet. Another is a cardiopulmonary exercise test (CPET). This involves moving a specially designed set of bicycle pedals using hands and arms. This will check how the lungs, heart and muscles are affected during exercise.

After the 12-month visit, people will visit the clinic every few months for up to a few years.

Primary Outcome Measures: Number of Participants with Treatment Emergent Adverse Events (TEAEs), A TEAE is defined as an AE observed after starting administration of the study intervention.

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Note: an AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures., Up to month 60|Number of Participants with Serious Adverse Events (SAEs), An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important events., Up to month 60|Number of participants with laboratory value abnormalities and/or AEs, Number of participants with potentially clinically significant laboratory values., Up to month 60|Number of participants with electrocardiogram (ECG) abnormalities and/or AEs, Number of participants with potentially clinically significant ECG values., Up to month 60|Number of participants with physical exam value abnormalities and/or AEs, Number of participants with potentially clinically significant physical exam values., Up to month 60
Secondary Outcome Measures: Change from baseline of frataxin protein level in cardiac tissue, Frataxin protein level in cardiac tissue will be recorded from endomyocardial biopsies collected by cardiac catheterization., Baseline, week 24 and week 52|Change from baseline of peak rate of oxygen consumption (VO2peak), VO2peak will be measured by upper extremity cardiopulmonary exercise testing (CPET)., Baseline, week 24 and week 52|Change from baseline of ventilatory anaerobic threshold (AT), AT will be measured by upper extremity CPET., Baseline, week 24 and week 52|Change from baseline of ventilation (VE)/volume of exhaled carbon dioxide (VCO2) slope, VE/VCO2 slope will be measured by upper extremity CPET., Baseline, week 24 and week 52|Change from baseline of left ventricular ejection fraction (LVEF), LVEF will be measured by echocardiogram (ECHO)., Baseline, week 24 and week 52|Change from baseline of left ventricular mass index (LVMI), LVMI will be measured by ECHO., Baseline, week 24 and week 52|Change from baseline of longitudinal cardiac strain, Longitudinal cardiac strain will be measured by ECHO., Baseline, week 24 and week 52|Change from baseline of vector copy number (VCN), VCN will be recorded from endomyocardial biopsies collected by cardiac catheterization., Baseline, week 24 and week 52|Change from baseline of total antibody (TAb) to adeno-associated virus 8 (AAV8), TAb to AAV8 will be recorded from serum samples collected., Baseline and up to week 52|Change from baseline of neutralizing antibody (NAb) to AAV8, NAb to AAV8 will be recorded from serum samples collected., Baseline and up to week 52|Change from baseline of TAb to frataxin, TAb to frataxin will be recorded from serum samples collected., Baseline and up to week 52