PrimeC for ALS

(PARADIGM Trial)

No longer recruiting at 6 trial locations

Overseen By Ferenc Tracik

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NeuroSense Therapeutics Ltd.

Must be taking: Riluzole, Edaravone

Must not be taking: NSAIDs, Celecoxib

Disqualifiers: Heart disease, Renal impairment, Epilepsy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PrimeC for people with ALS, a condition affecting nerve cells in the brain and spinal cord, leading to muscle weakness. The trial compares PrimeC to a placebo (a pill with no active ingredient) over six months to assess its safety and effectiveness. Those with ALS who have had symptoms for less than 30 months and experience muscle weakness may be suitable for this study. Participants will take four tablets a day and can continue using other ALS treatments if they have been stable on them for at least 60 days before joining. After six months, all participants will receive the actual treatment for another year to further evaluate its benefits. As a Phase 2 trial, this research measures how well PrimeC works in an initial, smaller group of people, offering participants a chance to contribute to important ALS treatment advancements.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain ALS treatments like riluzole, edaravone, sodium phenylbutyrate, and taurursodiol if they have been stable on them for at least 60 days before joining. However, if you are on chronic aspirin or NSAIDs and stopping them would be risky, you may not be eligible to participate.

Is there any evidence suggesting that PrimeC is likely to be safe for humans?

Research has shown that PrimeC has met safety and tolerability goals in studies. PrimeC combines two FDA-approved drugs: ciprofloxacin and celecoxib. Tests have assessed how well people can handle this combination. Studies found no major safety issues, and participants generally tolerated the treatment well.

Promising data also indicate that PrimeC positively affects certain biological markers, which could benefit people with ALS. These results support the short-term safety of PrimeC.

As further testing continues, researchers will closely monitor any new safety information. Prospective trial participants may find this background reassuring regarding the safety of PrimeC. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for ALS, like riluzole and edaravone, work by slowing the progression of the disease or reducing oxidative stress. But PrimeC works differently, targeting multiple pathways involved in ALS. It combines two active ingredients, ciprofloxacin and celecoxib, which aim to reduce inflammation and protect nerve cells. Researchers are excited about PrimeC's potential to offer a more comprehensive approach to managing ALS, possibly improving both survival and quality of life for patients.

What evidence suggests that PrimeC might be an effective treatment for ALS?

Research has shown that PrimeC, which participants in this trial may receive, may help slow the progression of ALS (amyotrophic lateral sclerosis). In one study, individuals taking PrimeC experienced a 36% slower progression of the disease compared to those who initially received a placebo (a non-active treatment) and then switched to PrimeC. Another study found a similar result, with a 32.8% reduction in the rate of disease progression. Additionally, lab tests on ALS models demonstrated that PrimeC improved the survival of motor neurons, the nerve cells affected by ALS. PrimeC also met important safety and effectiveness goals in earlier studies, showing benefits for both function and survival in people with ALS. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with ALS, who can understand and agree to the study terms. They must have an ALSFRS-R score ≥25, stable swallowing ability, a BMI between 18-30, disease duration less than 30 months from first symptom, and meet specific breathing capacity criteria. Women must meet reproductive standards. Exclusions include severe diabetes, heart issues, renal impairment, cognitive problems or other significant illnesses.

Inclusion Criteria

Your ALSFRS-R score at screening needs to be 25 or higher.

I can swallow without significant difficulty.

Your body mass index (BMI) is between 18 and 30.

Exclusion Criteria

My kidney function is impaired with high creatinine levels.

I use a tracheostomy or feeding tube.

I am a poor metabolizer for certain medications due to my CYP2C9 status.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the study drug or placebo twice daily for 6 months

6 months

Evaluations every 2 months for safety, tolerability, and efficacy

Open-label extension

Participants who complete the initial treatment phase switch to the active arm for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PrimeC

Trial Overview

The study tests PrimeC against a placebo in people with ALS. Participants are randomly assigned in a 2:1 ratio to either receive PrimeC or placebo twice daily for six months while continuing standard treatments like riluzole and edaravone. After six months of treatment, all participants will receive PrimeC during a year-long open label extension phase.

How Is the Trial Designed?

Group I: PrimeC Active Control 1 Intervention

2 tablets of PrimeC administered twice daily (4 tablets a day), at a daily dose of 1496 mg

Group II: Placebo Placebo Group 1 Intervention

2 tablets of Placebo administered twice daily (4 tablets a day). Placebo tablets are matched in size, color and taste.

Who Is Running the Clinical Trial?

NeuroSense Therapeutics Ltd.

Lead Sponsor

Trials

6

Recruited

150+

Citations

1.

neurology.org

neurology.org/doi/10.1212/WNL.0000000000211098

Shifting The PARADIGM: PrimeC, An Oral Candidate For ...

Results: At 12 months, PrimeC treatment attenuated disease progression (ALSFRS-R) by 36% compared to the placebo-to-PrimeC arm (Mean ...

2.

neurologylive.com

neurologylive.com/view/late-breaking-phase-2b-paradigm-data-support-continued-development-primec-als

Late-Breaking Phase 2b PARADIGM Data Support ...

Researchers also reported that PrimeC showed favorable safety and tolerability, slowing disease progression measured using the ALSFRS-R by 32.8% ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40283960/

Elucidating the Synergistic Effect of the PrimeC ...

Results: Motor neurons modeling ALS treated with the PrimeC combination exhibited better survival rates compared to treatment with either ...

4.

neurosense.investorroom.com

neurosense.investorroom.com/2024-12-04-NeuroSense-Announces-Completion-of-PARADIGM-Study-Highlighting-PrimeCs-Significant-Efficacy-and-Survival-Benefits-in-ALS

NeuroSense Announces Completion of PARADIGM Study ...

NeuroSense completed a Phase 2a clinical trial which met its safety and efficacy endpoints including reducing functional and respiratory ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05357950

Study Details | NCT05357950 | A Phase IIb, Multi-Center, ...

69 subjects with ALS will be enrolled in the study and randomized at a 2:1 ratio to receive the study drug or placebo tablets. Randomization sequences will ...

6.

neurosense.investorroom.com

neurosense.investorroom.com/2024-08-01-NeuroSense-Therapeutics-Announces-Positive-Biomarker-Data-from-ALS-Phase-2b-Clinical-Trial

NeuroSense Therapeutics Announces Positive Biomarker ...

12-month data demonstrated regulation of iron levels, which aligns with improved ALS survival and disease mitigation.

7.

als-mnd.org

als-mnd.org/support-for-pals-cals/drugs-in-development/neurosense-primcec/

NeuroSense – PrimeC

PrimeC is a combination therapy composed of two FDA approved drugs: ciprofloxacin and celecoxib. · PrimeC has shown promising data in preclinical models of ALS/ ...

8.

neurologylive.com

neurologylive.com/view/als-candidate-primec-meets-primary-safety-secondary-endpoints-phase-2b-paradigm-study

ALS Candidate PrimeC Meets Primary Safety and ...

PrimeC, NeuroSense's investigational amyotrophic lateral sclerosis (ALS) agent, achieved its primary safety and tolerability end points, along with secondary ...