First ALS Patient Enrolled in Phase 2b Study of NeuroSense’s PrimeC
PARADIGM (NCT05357950) is the company’s next step following the completion of a Phase 2a trial (NCT04165850) wherein the therapy effectively slowed disease progression when taken as an oral capsule three times daily for a year.
The six-month Phase 2b study will test an upgraded formulation of PrimeC versus a placebo in up to 69 adults with ALS. This is an extended-release formulation, meaning the medication is released in a controlled manner over a longer period. It will be available as oral tablets to be taken twice daily (two tablets at a time).
PARADIGM is recruiting participants at a single site in Israel, with additional locations in the U.S. and Italy to open in the future. Full enrollment is expected by year’s end, and top-line data are anticipated between April and June 2023.
“As PrimeC enters this advanced stage trial, we are hopeful that our enhanced formulation will further improve on the promising results we observed from our combination therapy in our Phase IIa ALS study,” Alon Ben-Noon, CEO of NeuroSense, said in a press release.
PrimeC is a fixed-dose combination of ciprofloxacin and celecoxib, two medications approved by the U.S. Food and Drug Administration for other indications. Ciprofloxacin is an antibiotic used to treat bacterial infections and celecoxib is an anti-inflammatory medication to relieve pain and inflammation.
Used together, they are expected to help slow or prevent ALS progression by targeting three mechanisms thought to contribute to ALS-associated neurodegeneration: brain inflammation, impaired microRNA regulation, and iron accumulation. MicroRNAs are small RNA molecules that control the activity of other genes.
In the previous Phase 2a trial involving 15 adults with ALS, one year of treatment with a total daily dose of 909 milligrams of PrimeC was found to be generally safe and well tolerated. It also slowed lung function decline and disability progression, as assessed with the ALS Functional Rating Scale Revised (ALSFRS-R).
The Phase 2b study will evaluate the safety and effectiveness of an optimized dose and improved formulation that’s expected to maximize the synergistic effect between the two medications, or how they work together to increase the effect of one another.
Participants, ages 18 to 75 and diagnosed up to 30 months before screening, will be randomly assigned to receive four daily capsules of either PrimeC (1,496 mg per day) or a placebo for six months. The placebo tablets will match those of PrimeC in size, color, and taste.
During the study, patients will be allowed to continue treatment with the approved ALS therapies riluzole (sold as Rilutek and other brand names) and Radicava (edaravone), as well as with sodium phenylbutyrate and taurursodiol — which are sometimes used off-label to treat ALS and were recently approved in combination under the brand name Albrioza.
In PARADIGM, scientists will look not only at side effects and discontinuation rates and reasons, but also at changes in functional disability (based on ALSFRS-R), lung function, quality of life, survival, and blood levels of ALS biomarkers.
Those completing the six-month period may choose to enter the study’s open-label extension portion, wherein all will receive the therapy for one year.
“In this well-designed, patient-centric study, we are working in collaboration with cutting-edge technology partners on an extensive panel of biomarkers to elucidate PrimeC’s mechanism of action, as we believe this could enable patient stratification and increase likelihood of success in a pivotal [trial],” Ben-Noon said. “Targeting multiple [disease-associated] pathways in ALS, synergistically, is a paradigm shift in ALS therapy.”
NeuroSense also is collaborating with Massachusetts General Hospital to study PrimeC’s effect on relevant targets in the brain by collecting and examining nerve cell-derived exosomes — tiny fatty vesicles filled with molecules that act as messengers to regulate several cellular processes. Findings are expected in the coming months.