NeuroSense taps machine learning to optimize PrimeC Phase 3 testing
PARADIGM trial is testing a long-acting formulation in 68 adults with ALS
NeuroSense Therapeutics is collaborating with PhaseV for insights into how to better design the protocol for the planned Phase 3 trial that will test PrimeC for amyotrophic lateral sclerosis (ALS).
A specialist in machine learning technology for clinical trials, PhaseV used data from the ongoing Phase 2b PARADIGM trial (NCT05357950) as input to a causal machine learning model. This is a form of artificial intelligence that can help unlock insights and identify features that may contribute to a treatment response.
As part of its independent analysis, the company found that PrimeC could work well in multiple subgroups of patients in the Phase 3 study, which should start in the coming months.
Being able to predict treatment outcomes in certain patients may help optimize the design of the upcoming trial by selecting the patients most likely to respond, while reducing costs.
ALS is a complex disease that manifests in unique ways in each patient. “Although there is an improved understanding of the underlying mechanisms of ALS, therapeutic options remain limited,” Raviv Pryluk, CEO and co-founder of PhaseV, said in a press release.
NeuroSense plans to submit an end-of-Phase 2 package for review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, the FDA’s European counterpart, and discuss the clinical protocol for the Phase 3 trial with the regulators.
“There remains a critical need for new innovative approaches to address this devastating neurodegenerative disease,” said Alon Ben-Noon, CEO of NeuroSense. “We plan to continue to collaborate with PhaseV as we develop our Phase 3 trial.”
Testing PrimeC in ALS
PrimeC contains fixed doses of two FDA-approved oral medications: the antibiotic ciprofloxacin and celecoxib, a pain killer that reduces inflammation. Both are expected to work together to slow or stop disease progression by blocking key mechanisms that lead up to ALS, such as inflammation, iron accumulation, and RNA processing.
PARADIGM is testing a long-acting formulation of PrimeC in 68 adults with ALS who started to see symptoms up to 2.5 years before enrolling. While continuing their standard ALS treatments, the participants were randomly assigned to PrimeC or a placebo, taken as two tablets twice daily for six months.
An analysis of PARADIGM’s per-protocol population — 62 adults with ALS who adhered well to the clinical protocol — showed a significant 37.4% reduction in functional decline, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
A subgroup of those patients who were at a higher risk for rapid disease progression had the most clinical benefit, with those treated with PrimeC for six months showing a significant, 43% reduction in functional decline over a placebo. High-risk patients made up about half the adults in the Phase 2b trial.
Another subgroup of newly diagnosed patients who’d had their first symptoms of ALS within a year of enrollment showed a 52% reduction in the rate of disease progression. This translated to a 7.76-point difference in favor of PrimeC on a maximum total of 48 points in the ALSFRS-R.
“Through our initial collaboration with PhaseV, we gained an even greater understanding of the effect of PrimeC across multiple patient subgroups,” Ben-Noon said. “We will apply these insights to optimize the design of our Phase 3 study with the aim of maximizing meaningful clinical results that will differentiate PrimeC in the market.”
“Through a unique combination of causal [machine learning], real-world data, and advanced statistical methods, we confirmed the potential clinical benefit of PrimeC,” Pryluk said. “Our analysis predicted a high rate of success for PrimeC in the Phase 3 clinical trial for multiple recommended subgroups.”
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