This is a Phase 1 open label trial investigating the safety, tolerability, and preliminary efficacy of ASP2016 in adults with Friedreich’s ataxia who are affected by cardiomyopathy. ASP2016 is a gene therapy designed to deliver a healthy copy of the FXN gene through an intravenous (IV) infusion.
Anyone considering participating in a clinical trial should discuss the matter with their physician. FARA does not endorse or recommend any particular studies.
Study Details:
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.
Key Inclusion Criteria:
- Participant has a diagnosis of FA with documentation of genetic testing that shows two GAA repeat expansions or one GAA repeat expansion with a pathogenic mutation (such as a point mutation)
- Participant has a resting LVEF between 40-55% as measured by echocardiogram
- Participant has a body mass index between 17-33 kg/m2
Key Exclusion Criteria:
- Participant has late onset FA (symptom onset after the age of 25 years)
- Participant is unable to complete cardiopulmonary exercise testing
- Participant cannot undergo cardiac MRI with contrast
- Participant has an elevated titer of anti-AAV8 total antibodies
- Participant has significant cardiac fibrosis
Criteria Pertaining to Omaveloxolone (Skyclarys)
- Participants who are not taking omaveloxolone agree not to begin omaveloxolone treatment during the 52-week period after receiving the dose of ASP2016
- Participants who are taking omaveloxolone
- Need to have been taking it for a minimum of three months
- Must have liver function test levels that pass diagnostic assessment exclusion criteria
- Must stop taking omaveloxolone until 52 weeks post treatment if there is a liver function test elevation after treatment with ASP2016
- Participants who have discontinued omaveloxolone prior to enrolling in this trial must have taken their last dose of omaveloxolone at least three weeks prior and pass liver function tests
Additional inclusion and exclusion criteria may apply and will be evaluated by a study doctor.
Length of Study Commitment: 5 years