PARADIGM trial of PrimeC in treating ALS nears full enrollment

Study into safety, potential efficacy of therapy as extended-release tablet

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by Andrea Lobo |

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A Phase 2b trial that’s testing PrimeC in people with amyotrophic lateral sclerosis (ALS) has reached 80% enrollment and is on track to complete patient recruitment by June, NeuroSense Therapeutics announced in a quarterly update.

Called PARADIGM (NCT05357950), the study began enrolling ALS patients in mid-2022, and it plans to include up to 69 adults recently diagnosed with ALS, ages 18-75, at sites in Israel, Italy, Germany, and Canada. Top-line results are expected later this year. For those interested in possibly taking part, contact information is available.

“We are … well on our way to completing patient enrollment in our Phase 2b ALS study,” Alon Ben-Noon, CEO of NeuroSense Therapeutics, said in a company press release.

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PrimeC is fixed-dose combination of an antibiotic and anti-inflammatory

PrimeC is composed of a fixed-dose combination ciprofloxacin, an antibiotic, and celecoxib, an anti-inflammatory agent. Both medications are individually approved in the U.S. and have an established safety profile.

The combination is thought to lower inflammation in the nervous system, improve RNA processing, and normalize iron accumulation. Problems in these areas help to drive disease progression.

In an ALS fish model, PrimeC was reported to significantly outperform standard ALS treatments, improving motor abilities and the function of motor neurons, the cells damaged in ALS. It also helped restore neuromuscular junctions, the regions where nerves and muscles communicate.

In a previous Phase 2a trial (NCT04165850) in 15 ALS patients, oral PrimeC was found to be safe and well tolerated, and to lower disease biomarkers. Findings also suggested a slowing of disease progression compared with an historical group of patients.

The PARADIGM trial now is testing an extended-release formulation of PrimeC in ALS patients with disease onset less than 30 months, about 2.5 years, before a screening for the study.

Participants are being randomly assigned to PrimeC — given as two extended-release tablets twice daily, for a total daily 1,496 mg dose — or to placebo tablets for six months, while continuing on their standard ALS medications.

The study’s primary goals are to determine treatment safety, and changes in ALS biomarkers with treatment. Secondary measures include changes in functional disability, lung function, and quality of life.

After completing the trial’s randomized phase, patients will have the option to join an open-label extension phase, in which all will be treated with PrimeC for up to one year.

Of note, patients in the U.S. were expected to enroll in PARADIGM, but the company decided against opening sites there after the U.S. Food and Drug Administration requested more data to support the trial’s duration.

Should PARADIGM conclude successfully, NeuroSense plans to meet with the regulatory agency to include U.S. sites in a pivotal Phase 3 trial.

Under a collaboration with researchers at Massachusetts General Hospital, the company also aims to study PrimeC’s effects on key ALS processes. Particularly, it is looking into the buildup of TDP-43, a protein that’s abnormal in most disease cases; cellular recycling; and oxidative stress, the imbalance between the production of oxygen-containing molecules and the body’s ability to clear them.

“We continue to form collaborations with leading institutions and innovative companies to advance the science of biomarkers in the diagnosis and treatment of neurological diseases,” Ben-Noon said.

PrimeC has received orphan drug status from the FDA and European Medicines Agency (EMA), a designation meant to support and accelerate the development of potentially life-saving treatments for rare diseases.