PARADIGM trial of PrimeC for ALS now fully enrolled with 69 adults

NeuroSense looking for safety, efficacy to exceed earlier results

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by Andrea Lobo |

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A Phase 2b trial of PrimeC for people with amyotrophic lateral sclerosis (ALS) has completed patient enrollment, according to NeuroSense Therapeutics, the therapy’s developer.

Called PARADIGM (NCT05357950), the study enrolled 69 adults diagnosed with ALS, ages 18-75, at sites in Israel, Italy, and Canada. The company anticipates top-line results late this year.

The trial is testing an extended-release formulation of PrimeC, designed to require less frequent dosing for patients.

“Based on the new formulation, we are aiming for efficacy and safety results that will meet and exceed the results achieved in the Phase 2a study,” Vivian Drory, MD, principal investigator of the PARADIGM trial at Tel Aviv Sourasky Medical Center, in Israel, said in a company press release.

Results from this study will inform the design of a future pivotal Phase 3 clinical trial of PrimeC, the company said.

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PrimeC is an oral, fixed-dose combination of two medications approved in the U.S. that both have well-established safety profiles. One, ciprofloxacin, is an antibiotic, while the other, celecoxib, is an anti-inflammatory agent.

The combination is thought to potentially inhibit disease progression by targeting key mechanisms in ALS motor degeneration. Specifically, the therapy aims to block inflammation, iron accumulation, and impaired RNA processing.

An initial formulation of PrimeC was found to be safe and well tolerated, and showed some promising trends toward less functional and respiratory decline, in a previous Phase 2a trial (NCT04165850). That trial involved 15 ALS patients.

The PARADIGM trial was designed to test a longer-acting formulation of PrimeC, which may be administered less frequently because it releases the two medications over an extended period of time.

The trial enrolled ALS patients whose symptoms of muscle weakness began less then 30 months (about 2.5 years) before screening. All participants were randomly assigned to receive Prime C, at a total daily dose of 1,496 mg — two tablets twice daily — or a placebo, for six months. All patients maintained their standard ALS medication regimen during the trial.

The study primarily aims to evaluate the treatment’s safety and tolerability, as well as changes in ALS biomarkers associated with PrimeC treatment. Secondary measures include changes in patients’ functional disability, lung function, quality of life, and survival.

“PARADIGM is tracking 17 different outcome measures while the primary endpoint remains focused on biomarkers,“ said Ferenc Tracik, MD, chief medical officer at NeuroSense.

“This wealth of outcome data will not only be used to optimize the design of a future pivotal Phase 3 study for PrimeC, but we believe it will provide greater insight into the mechanisms of ALS for the scientific community as we advance toward a day when ALS will become a highly treatable disease,” Tracik said.

After completing the trial’s randomized phase, patients will have the option to enter an open-label extension phase, during which all participants will receive PrimeC for one year. To date, 26 participants completed the randomized phase, and 25 chose to continue into the extension part.

“It is highly encouraging that nearly all participants who completed the study have elected to continue in the [open label extension] phase with the treatment of PrimeC,” Drory said.

“We look forward to seeing the topline data from this study,” Drory added, noting the trial is testing the “optimized formulation of PrimeC.”

PrimeC has been granted orphan drug status in both the U.S. and the European Union. This designation is awarded to therapies that aim to treat rare diseases.

“We are pleased to share this milestone for the PARADIGM clinical trial,” said Alon Ben-Noon, CEO of NeuroSense, adding, “We are grateful to the participants living with ALS, their families, and the study investigators for their commitment to the PARADIGM trial and for taking part in our mission to develop an effective therapy for ALS.”