PRX002/RG7935 (PRX002), an anti-α-synuclein monoclonal antibody, has demonstrated acceptable safety and tolerability in patients with Parkinson disease, according to a study published in JAMA Neurology.
This randomized double-blind multiple ascending-dose trial included 80 participants randomly assigned to receive intravenous PRX002 at 0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 10 mg/kg, 30 mg/kg, or 60 mg/kg, or a placebo dose. Study participants were administered 3 doses each month and monitored for 6 months. The treatment-emergent adverse events that occurred included 5 cases of constipation, 4 cases of infusion reaction, and 3 cases each of diarrhea, headache, peripheral edema, post-lumbar puncture syndrome, and infection of the upper respiratory tract. No serious or severe treatment-emergent adverse events occurred. Antibodies developing against the drug were not detected.
The serum levels of PRX002 increased as expected, and mean terminal elimination half-life was 10.2 days across different doses. A 97% reduction in free serum α-synuclein levels was observed after a single dose of PRX002 at the highest concentration (F 78,284=1.66; P =.002), with comparable reductions after 2 more doses. In each group, the concentration of PRX002 in the cerebrospinal fluid increased with dose to approximately 0.3% relative to serum.
Of the 80 participants in this study, 78 were white and 64 were men, with a median age of 58±8.4 years. The study was performed at 8 study centers in the United States between July 2014 and September 2016 and enrolled participants with idiopathic Parkinson disease of mild to moderate severity. The researchers assessed safety and tolerability through neurological and physical exams, vital signs, laboratory tests, and adverse events.
The researchers conclude that “[single] and multiple doses of PRX002 were generally safe and well tolerated and resulted in robust binding of peripheral α-synuclein and dose-dependent increases of PRX002 in cerebrospinal fluid, reaching cerebrospinal fluid concentrations that may be expected to engage extracellular aggregated α-synuclein in the brain. Findings support the design of an ongoing phase 2 clinical study (Clinicaltrials.gov identifier: NCT03100149).”
This study was sponsored by Prothena Biosciences Limited and F. Hoffmann-La Roche Ltd. Please refer to reference for a complete list of authors’ disclosures.
Jankovic J, Goodman I, Safirstein B, et al. Safety and tolerability of multiple ascending doses of PRX002/RG7935, an anti-α-synuclein monoclonal antibody, in patients with Parkinson disease: A randomized clinical trial [published online June 18, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.1487