PrimeC for ALS Shows Safety, Good Profile as Extended-release Tablet

Phase 1 work supports formulation being used in Phase 2b PARADIGM trial

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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An extended-release formulation of PrimeC, an investigational combination therapy for amyotrophic lateral sclerosis (ALS), demonstrated a favorable pharmacokinetic profile in healthy adults in a Phase 1 trial, helping with an ongoing Phase 2b study and work into a potential pivotal trial in ALS patients.

A pharmacokinetic (PK) study aims to learn more about how the body handles a treatment by measuring its movement into, through, and out of the body over time. Such studies can help in developing the most appropriate dosing strategy for a given medication.

Results from this PK study (NCT05436678) continue to support the medication’s safety, PrimeC’s developer, NeuroSense Therapeutics, said in a company press release. They also support the extended-release tablet formulation that’s being used in the ongoing Phase 2b PARADIGM trial (NCT05357950), it added.

Data from both these trials ultimately will help in designing a larger and pivotal Phase 3 study of PrimeC in ALS patients.

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“With this additional multi-dose PK study, we have achieved another important milestone in our PrimeC ALS development plan,” Ferenc Tracik, MD, chief medical officer at NeuroSense, said in a company press release.

Prime C is a fixed-dose combination of two approved medications, celecoxib and ciprofloxacin. Celecoxib is an anti-inflammatory treatment while ciprofloxacin is an antibiotic. Together, the two medications are expected to ease inflammation and prevent other processes involved in ALS progression.

PARADIGM trial testing extended-release PrimeC against a placebo

The combo therapy has earned orphan drug status in the U.S. and Europe, a designation given to potential treatments for rare diseases to help speed and support their development and potential regulatory review, including a period of market exclusivity if approved.

An initial, open-label Phase 2a trial (NCT04165850) evaluated PrimeC, taken orally three times a day (909 mg total daily dose) for a year, in 15 ALS patients. Results showed the therapy was safe and lowered disease biomarkers, and they also suggested it could slow disease progression.

The Phase 2b PARADIGM trial is testing an upgraded, extended-release formulation of the medication at an optimized total daily dose of 1,496 mg. The extended-release formulation, releasing its two compounds in a slow and controlled manner, is expected to “maximize the synergism between the compounds over a longer period of time,” NeuroSense stated.

A six-month study, PARADIGM is comparing PrimeC against a placebo in up to 69 adults, ages 18 to 75, recently diagnosed with ALS (first symptoms within 30 months, about 2.5 years, before enrollment). Participants are randomly assigned to two Prime C tablets taken every 12 hours or to placebo tablets on a similar schedule. All enrolled can continue with their standard ALS therapies.

The trial is recruiting eligible patients at a single site in Israel. Additional locations in the U.S. and Italy may also open, NeuroSense has reported.

PARADIGM’s main goals are to assess the treatment’s safety and effects on key ALS biomarkers. Changes in functional disability, quality of life, lung function, survival, and additional disease biomarkers will also be measured.

Those who complete the Phase 2b study may choose to enter its open-label extension phase, during which all will receive PrimeC for a year.

The PK study evaluated Prime C in an extended-release formulation against its individual components. Twenty adults were initially given either two PrimeC tablets (total of 748 mg) or a 750 mg ciprofloxacin tablet with a 200 mg celecoxib tablet twice daily for 6.5 days (13 total administrations). Doses were taken after a meal.

Conditions were then switched, meaning that people originally taking PrimeC were given the individual treatments, and vice versa, for 6.5 more days.

Blood samples were collected to measure concentrations of the medications in the bloodstream throughout treatment.

Results indicated that PrimeC has a favorable PK profile, with drug concentrations consistently in a therapeutic range for an extended period of time. They also further supported the extended-release formulation and dosing regimen being used in PARADIGM, the company reported.

“The results confirm the favorable safety and improved PK profile of PrimeC in this unique formulation,” Tracik said.