PrimeC Demonstrates Positive Results on End Points in ALS Trial

PrimeC (ciprofloxacin and celecoxib extended release; NeuroSense Therapeutics, Cambridge, MA) was safe and generally well tolerated in people with amyotrophic lateral sclerosis (ALS), according to peer-reviewed results from the phase 2b PARADIGM randomized clinical trial (NCT05357950) published in JAMA Neurology. Although the study was not powered to establish clinical efficacy, investigators reported exploratory functional, complication-free survival, and biomarker findings supporting further study. Practical Neurology previously reported extended survival findings from PARADIGM; the peer-reviewed publication provides additional safety, functional, and biomarker context from the randomized phase 2b trial.

PARADIGM was a randomized, double-blind, placebo-controlled phase 2b trial conducted at 4 ALS referral centers in Italy, Canada, and Israel from May 2022 to November 2023. Adults with definite or probable ALS and disease duration of 30 months or less were eligible. Of 73 screened participants, 69 were randomized and 68 were included in the intent-to-treat population. Participants were randomly assigned 2:1 to receive PrimeC tablets or placebo for 6 months, followed by a 12-month open-label extension in which all participants received PrimeC.

The primary end point was safety and tolerability. The prespecified primary biomarker outcome was plasma neuron-derived exosomal TAR DNA-binding protein 43 or prostaglandin J2, but those analyses remain under development and will be reported separately. Secondary outcomes included change in ALS Functional Rating Scale–Revised (ALSFRS-R) score, survival, and time-to-composite events.

Inside the PARADIGM Results

• Treatment-emergent adverse events occurred in 66.7% of participants receiving PrimeC and 65.2% receiving placebo during the double-blind period.
• Drug-related adverse events were more frequent with PrimeC than placebo (20.0% vs 4.3%) and were mostly mild to moderate and transient.
• At month 6, the mean ALSFRS-R difference between PrimeC and placebo was 2.23 points, but this did not reach statistical significance (95% CI, −0.61 to 5.07; P=.12).
• At month 18, participants originally randomized to PrimeC had a 7.92-point ALSFRS-R difference compared with those initially assigned to placebo (95% CI, 2.25 to 13.60; P=.007).
• Continuous PrimeC treatment was associated with a lower risk of ALS-related complications, including hospitalization, respiratory failure, or death (hazard ratio, 0.36; 95% CI, 0.15 to 0.85; P=.02).

Exploratory biomarker analyses showed preservation of transferrin levels with PrimeC during the double-blind period and downregulation of several ALS-associated microRNAs, including miR-199a-3p, miR-199a-5p, miR-181a-5p, and miR-181b-5p. Neurofilament light levels did not differ significantly between treatment groups.

The authors noted several limitations, including the phase 2 sample size, lack of power for definitive efficacy or survival conclusions, absence of multiplicity adjustment for secondary and exploratory end points, and the trial design in which all participants received active treatment after 6 months. They state that the safety, functional, and biomarker findings support confirmatory evaluation of PrimeC in ALS.

Source

Cudkowicz M, Drory VE, Chio A, et al. Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial. JAMA Neurol. 2026;83(5):471–480. doi:10.1001/jamaneurol.2026.0230