Three clinical centers are now open for enrollment — Collaborative Neuroscience Network in California, USF Ataxia Research Center in Florida, and the Children’s Hospital of Philadelphia, in Pennsylvania — with plans for two additional centers to open soon. More information on contacts and locations can be found here.
RT001 is a stabilized version of linoleic acid, a natural and essential fat. It was designed to substitute natural fats, known as polyunsaturated fatty acids (PUFAs), in cell membranes in order to fortify cells against damage.
Oxidative stress in cells and in mitochondria, in particular, is suspected to be one of the primary sources of nerve cell death underlying several degenerative diseases, including Friedreich’s ataxia.
Patients were randomized to one of two oral doses of RT001 (1.8 or 9 grams/day) or an inactive placebo. Treatment continued for 28 days, after which researchers assessed the study’s primary goals of safety and tolerability.
Patients taking RT001 outperformed those on placebo, showing a higher peak workload (a measure of fitness capacity) in a cardiopulmonary exercise test (CPET) done on a cycle ergometer.
Although the short duration of the study (one month) was insufficient to detect significant changes in other measures of disease progression, there were positive trends toward improvements in Friedreich’s Ataxia Rating Scale-Neurological (FARS-Neuro) scores, which measures progression in FA patients, as well as peak oxygen consumption, and stride speed during exercise.
The treatment was safe and well-tolerated.
The current Phase 2/3 trial (NCT04102501) will further validate the effectiveness, and determine long term safety and tolerability of RT001 in adults with Friedreich’s ataxia.
The study expects to enroll 60 patients, who will be assigned randomly to either treatment with RT001 — nine capsules daily (8.64 g total dose) during the first month, followed by six capsules daily (5.76 g total dose) after the first month of treatment — or an inactive placebo.
The primary measure of RT001’s effectiveness is the change in peak workload, from study start to 11 months on treatment, measured on a CPET.
Secondary measures include distance walked during a one minute test and modified Friedreich’s ataxia rating scale (mFARS) scores, which is a physician-assessed measurement of activities such as speaking and swallowing, upper limb coordination, lower limb coordination, and standing and walking.
Patient-reported fatigue, as well as illness severity and therapeutic response as rated by a clinician, also will be measured.
“This Phase 2/3 clinical trial is an important milestone in the development pathway of RT001” Peter G. Milner, MD, of Retrotope, said in a press release.
“We believe the CPET is a very sensitive probe of the mitochondrial function and stamina of patients with this disease who suffer from profound fatigue due to mitochondrial neuropathy, myopathy and cardiomyopathy. FDA has agreed with us that CPET may be a primary endpoint in a marketing approval study, and will be evaluated for approval with other secondary, supportive efficacy measures and validated scales important to patient function,” he said.
RT001 was granted orphan drug designation for the treatment of Friedreich’s ataxia by the FDA in 2016.
Retrotope also is developing the therapy for infantile neuroaxonal dystrophy (INAD), another severe neurodegenerative disease.