NeuroSense Therapeutics is working with PhaseV to gain insight into how to better design protocols for a planned Phase 3 trial testing PrimeC against amyotrophic lateral sclerosis (ALS).
PhaseV, an expert in machine learning technology for clinical trials, used data from the ongoing Phase 2b PARADIGM trial (NCT05357950) as input to a causal machine learning model. This is a type of artificial intelligence that helps unlock insights and identify characteristics that may contribute to treatment response.
As part of an independent analysis, the company found that PrimeC may perform well in multiple patient subgroups in a Phase 3 trial expected to begin in the coming months.
Being able to predict treatment outcomes for specific patients could help optimize the design of future clinical trials by selecting patients most likely to respond while reducing costs.
ALS is a complex disease with symptoms that vary from patient to patient. “Despite advances in understanding the mechanisms underlying ALS, treatment options remain limited,” Raviv Pryluk, CEO and co-founder of PhaseV, said in a press release.
Neurosense will submit the end-of-Phase 2 study package to the U.S. Food and Drug Administration (FDA) and the FDA's European counterpart, the European Medicines Agency, and will discuss clinical protocols for the Phase 3 study with regulators. It's a schedule.
“New and innovative approaches to addressing this devastating neurodegenerative disease remain critically needed,” said Alon Ben Noon, CEO of NeuroSense. “We will continue to collaborate with Phase V as we develop the Phase 3 trial.”
Testing PrimeC in ALS
PrimeC contains fixed doses of two FDA-approved oral medications: the antibiotic ciprofloxacin and the anti-inflammatory painkiller celecoxib. Together, both are expected to slow or stop disease progression by blocking key mechanisms that lead to ALS, including inflammation, iron accumulation, and RNA processing.
PARADIGM is testing its long-acting PrimeC formulation in 68 adults with ALS whose symptoms began 2.5 years before enrollment. Participants were randomly assigned to PrimeC or a placebo, two tablets twice a day, for six months while continuing their standard ALS treatment.
Analysis of the PARADIGM per-protocol population (62 adults with ALS who adhered to the clinical protocol) demonstrated a significant 37.4% reduction in functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). I did.
The subgroup of patients at high risk of rapid disease progression saw the greatest clinical benefit, with patients treated with PrimeC for six months showing a significant 43% reduction in functional decline compared to placebo. High-risk patients represented approximately half of the adults in the Phase 2b trial.
Another subgroup of newly diagnosed patients who developed their first symptoms of ALS within a year of enrollment showed a 52% reduction in the rate of disease progression. This results in a maximum total of 48 points for ALSFRS-R, which is a 7.76 point lead over PrimeC.
“Through our initial collaboration with PhaseV, we were able to further understand the effects of PrimeC across multiple patient subgroups,” said Ben-Noon. “We will apply these insights to optimize the design of the Phase 3 trial and aim to maximize the meaningful clinical results that differentiate his PrimeC in the market.”
“Through a unique combination of causal relationships, [machine learning], real-world data, and advanced statistical techniques to confirm the potential clinical benefits of PrimeC,” said Priluk. “Our analysis predicted high success rates for PrimeC in Phase 3 clinical trials across multiple recommended subgroups.”
