A Phase IIb, Multi-Center, Multinational, Double-Blind, Placebo-Controlled Study, With an Open Label Extension, to Evaluate Safety, Tolerability and Efficacy of PrimeC in Subjects With ALS

NCT05357950 | Completed Phase 2 FDA Drug

• 1 other identifier: NST003
• Study Type: interventional
• Target: 69
• Locations: 3 countries
• Sites: 4

Brief Summary

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 be in random block sizes and stratified for ENCALS risk category \[high risk ≥ -4.5 vs. low risk \< -4.5\], and for background ALS treatment (riluzole and/or edaravone and/or sodium phenylbutyrate and/or taurursodiol) vs. no background ALS treatment. All subjects will be administered the drug/placebo twice daily (BID), two tablets each time, for 6 months. Subjects will be allowed to receive standard of care (SOC) treatment of approved products (i.e., riluzole and edaravone). Additionally, subjects will be allowed to receive treatment with off-label sodium phenylbutyrate and taurursodiol, which are accepted for ALS treatment. Subjects will be evaluated every 2 months for safety, tolerability (adverse events, safety laboratory, vital signs, ECG, withdrawal rates and reasons) and efficacy (e.g. biomarkers, clinical outcomes (ALSFRS-R and SVC, quality of life and survival). All subjects who complete the 6 months dosing will be switched to the active arm for a 12-month open label extension (OLE).

Conditions

Amyotrophic Lateral Sclerosis; ALS

Outcome Measures

Primary Outcomes (6)

• Incidence and severity of treatment-emergent adverse events (TEAEs)

  Treatment emergent adverse event is any medical event associated with the drug

  6 months

• Number of subjects who discontinued treatment prematurely

  Number of subjects whose treatment is stopped prematurely for any reason

  6 months

• Number of patients who discontinued treatment prematurely due to adverse events

  Number of patients whose treatment is stopped prematurely specifically due to adverse events

  6 months

• Number of patients with clinically significant abnormal laboratory values

  6 months

• The mean difference between PrimeC and Placebo in serum concentration of NDE TDP-43 at month 6

  6 months

• The mean difference between PrimeC and placebo in serum concentration of NDE PgJ2 at month 6

  6 months

Secondary Outcomes (8)

• Change from baseline to 6 months in ALS functional rating scale - revised (ALSFRS-R)

  6 months

• Change from baseline to 6 months in slow vital capacity (SVC)

  6 months

• Change from baseline to 6 months in quality of life ALSSQOL-SF

  6 months

• Change from baseline to 6 months in PROMIS-10 quality of life questionnaire

  6 months

• Survival at 6 months of treatment

  6 months

Other Outcomes (3)

• Change from baseline to 6 months in the following serum biomarkers: serum ferritin, transferrin, iron, neurofilaments and exosomal LC3, Dicer, and other biomarkers evaluating the effect of PrimeC on pathophysiological mechanisms in ALS

  6 months

• Effect of PrimeC versus placebo on the time to reach advanced disease stages (King's/MiToS)

  6 months

• Change from baseline to 6 months in Patient-ranked order of function (PROOF)

  6 months

Study Arms (2)

PrimeC

ACTIVE COMPARATOR

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

Drug: PrimeC

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

PrimeC DRUG

Ciprofloxacin and celecoxib combination extended release formulation

PrimeC

Placebo DRUG

Placebo matches active drug in size, color and taste

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to comprehend and willing to sign an informed consent form (ICF)
• Males or females between the ages of 18 and 75 years of age, inclusive
• Diagnosis of familial or sporadic ALS (defined as meeting the laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the Gold Coast criteria)
• Disease duration after first symptom (muscle weakness) less than 30 months prior to screening
• Pre-enrollment ALSFRS-R slope from disease onset ≥ 0.3 points per month
• ALSFRS-R at screening ≥ 25
• Item 3 (swallowing) in ALSFRS-R ≥ 3
• Subjects may be treated in parallel with riluzole and/or edaravone and/or sodium phenylbutyrate and/or taurursodiol; 60 days of stable use prior to enrollment is required
• Upright slow vital capacity (SVC) ≥ 60% of predicted for age, height, weight and sex at screening according to the GLI-2012
• \< BMI \< 30
• A caregiver (if one is needed)
• Female subjects must be post-menopausal (≥ 1 year) OR sterilized, OR if of childbearing potential (i.e., females who have had their first period unless they are anatomically or physiologically incapable to become pregnant), must have a negative pregnancy test, and agree to use contraceptive drugs or devices (e.g., diaphragm plus spermicide, or oral contraceptives) for the duration of the study and 10 weeks after the last treatment dose AND require male partners to use a condom during sexual intercourse

You may not qualify if:

• A past history of adverse reaction/hypersensitivity to either NSAIDs, celecoxib or fluoroquinolones, ciprofloxacin
• Any known clinically significant abnormal gastric mucosal erosion, ulcer or tumor or/and GI disorder and/or bariatric surgery
• Known history of clinically significant impairment of renal function (creatinine ≥ 1.5)
• Known or suspected symptomatic congestive heart and/or coronary heart disease, previous history of myocardial infarction, uncontrolled arterial hypertension, or rhythm abnormalities requiring permanent treatment
• Known history of QT/QTc prolongation, Torsade de pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT syndrome) and the use of concomitant medications that prolong the QT/QTc interval
• Known or suspected diagnosis or family history of epilepsy in first degree relatives
• Known predisposition to tendinitis
• Known or suspected to be a poor CYP2C9 metabolizers who also uses pharmacologic agents (prescription or over-the-counter) or herbal products known or suspected to induce or inhibit CYP2C9 within 30 days before enrollment
• Tracheostomy or percutaneous gastrostomy use
• Presence at screening of any medically significant cardiac, pulmonary, musculoskeletal, or psychiatric illness that might interfere with the subject's ability to comply with study procedures or that might confound the interpretation of clinical safety data, including, but not limited to:
• Mean systolic blood pressure \>160 mm Hg and/or mean diastolic blood pressure \>100 mm Hg (measurements taken after a few minutes rest) that persist on 3 successive measurements taken at least 2 minutes apart
• NYHA Class II or greater congestive heart failure
• Chronic obstructive pulmonary disease or asthma requiring daily use of bronchodilator medications
• Poorly controlled or brittle diabetes mellitus
• Cognitive impairment, related to ALS or otherwise, sufficient to impair subject's ability to understand and/or comply with study procedures and provide informed consent

Sponsors & Collaborators

• NeuroSense Therapeutics Ltd.: lead

Study Sites (4)

Lawson Health Research Institute

London, Ontario, Canada

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

IRCCS Istituti clinici Maugeri

Milan, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino

Torino, Italy

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: May 31, 2022
• Primary Completion: November 2, 2023
• Study Completion: November 4, 2024
• Last Updated: September 5, 2025

Record last verified: 2025-07

Locations

CA (1); IT (2); IL (1)