Cardiomyopathy, Friedreich Ataxia
Conditions
Keywords
ASP2016, Friedreich Ataxia Cardiomyopathy, Frataxin, Friedreichs Ataxia, Heart, Gene Therapy
Brief 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.
Interventions
GENETICASP2016
Intravenous (IV) infusion
DRUGPrednisolone
Oral
Sponsors
Astellas Gene Therapies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Participant has both a clinical diagnosis of Friedreich ataxia (FA) and a documented history of genetic diagnosis of FA with either a guanine-adenine-adenine (GAA) trinucleotide repeat (TNR) expansion in intron 1 of both gene for frataxin (FXN) alleles or a GAA TNR expansion of intron 1 of one FXN allele and a pathogenic variant in the other FXN allele. * Participant has a resting LVEF ≥ 40% and \< 55% as measured at screening by ECHO. * Participant has a body mass index range of 17.0 to 30.0 kg/m2. * Participant agrees not to begin omaveloxolone treatment during the 52-week period after receiving study intervention. * Participants on omaveloxolone, who opt to discontinue omaveloxolone, may enroll if they stop omaveloxolone for 3 weeks and pass study screening, including LFTs. * Participants on omaveloxolone, who opt to stay on omaveloxolone will need to have been on it for a minimum of 3 months, with LFTs that pass diagnostic assessments
Exclusion criteria
at screening and prior to dosing with ASP2016. Prior elevation(s) in AST/ALT associated with omaveloxolone use must be discussed with the sponsor medical monitor. If there is a liver function test (LFT) elevation after treatment, participant agrees to stop omaveloxolone treatment until 52 weeks. * Participants on omaveloxolone will need to discontinue strong or moderate cytochrome P450 3A4 (CYP3A4) inducers and inhibitors. * Woman of Child Bearing Potential (WOCBP) on omaveloxolone must use a nonhormonal, highly effective methods of contraception (e.g., nonhormonal intrauterine device system), as omaveloxolone may interfere with hormonal methods of contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | Up to month 60 | 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. |
| Number of Participants with Serious Adverse Events (SAEs) | Up to month 60 | 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. |
| Number of participants with laboratory value abnormalities and/or AEs | Up to month 60 | Number of participants with potentially clinically significant laboratory values. |
| Number of participants with electrocardiogram (ECG) abnormalities and/or AEs | Up to month 60 | Number of participants with potentially clinically significant ECG values. |
| Number of participants with physical exam value abnormalities and/or AEs | Up to month 60 | Number of participants with potentially clinically significant physical exam values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of left ventricular mass index (LVMI) | Baseline, week 24 and week 52 | LVMI will be measured by ECHO. |
| Change from baseline of longitudinal cardiac strain | Baseline, week 24 and week 52 | Longitudinal cardiac strain will be measured by ECHO. |
| Change from baseline of vector copy number (VCN) | Baseline, week 24 and week 52 | VCN will be recorded from endomyocardial biopsies collected by cardiac catheterization. |
| Change from baseline of frataxin protein level in cardiac tissue | Baseline, week 24 and week 52 | Frataxin protein level in cardiac tissue will be recorded from endomyocardial biopsies collected by cardiac catheterization. |
| Change from baseline of neutralizing antibody (NAb) to AAV8 | Baseline and up to week 52 | NAb to AAV8 will be recorded from serum samples collected. |
| Change from baseline of TAb to frataxin | Baseline and up to week 52 | TAb to frataxin will be recorded from serum samples collected. |
| Change from baseline of total antibody (TAb) to adeno-associated virus 8 (AAV8) | Baseline and up to week 52 | TAb to AAV8 will be recorded from serum samples collected. |
| Change from baseline of peak rate of oxygen consumption (VO2peak) | Baseline, week 24 and week 52 | VO2peak will be measured by upper extremity cardiopulmonary exercise testing (CPET). |
| Change from baseline of ventilatory anaerobic threshold (AT) | Baseline, week 24 and week 52 | AT will be measured by upper extremity CPET. |
| Change from baseline of ventilation (VE)/volume of exhaled carbon dioxide (VCO2) slope | Baseline, week 24 and week 52 | VE/VCO2 slope will be measured by upper extremity CPET. |
| Change from baseline of left ventricular ejection fraction (LVEF) | Baseline, week 24 and week 52 | LVEF will be measured by echocardiogram (ECHO). |
Outcome results
None listed