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Amyotrophic Lateral SclerosisPhase 2PARADIGMNCT05357950

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

A Phase 2 study testing PrimeC in people with Amyotrophic Lateral Sclerosis and ALS, run by NeuroSense Therapeutics Ltd. at 4 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Amyotrophic Lateral Sclerosis, ALS
What is being tested?
PrimeC
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
69 participants
Where
4 sitesin 3 countries
Study dates
31 May 2022to 4 Nov 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 18 < 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

Who cannot join

  • 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
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  • 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
  • Subject who is treated with chronic aspirin or NSAIDs and is at risk if stopped. Clopidogrel is allowed and can replace Aspirin.
  • Any contraindication for ciprofloxacin and celecoxib according to the current prescribing information.
  • Female who is pregnant or breastfeeding or with intention of becoming pregnant during the course of the study.
  • Any impairment or social circumstance that, in the opinion of the Investigator, would render the subject not suitable to participate in the study.
  • Subject, or subject's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
  • Subject is participating in (or plans to participate in) any other investigational drug trial, or plans to be exposed to any other investigational agent, device and/or procedure, from 30 days prior to Screening through study completion.

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

Italy2 sites

  • IRCCS Istituti clinici Maugeri

    Milan

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

    Torino

Other trials in Italy

Canada1 site

  • Lawson Health Research Institute

    London, Ontario

Other trials in Canada

Israel1 site

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

About this study

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

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.

Read more

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).

Being tested
PrimeC, Placebo
Medical subject headings
Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrimeCDrug

    Ciprofloxacin and celecoxib combination extended release formulation

  • PlaceboDrug

    Placebo matches active drug in size, color and taste

Study groups in NCT05357950
Study groupRoleWhat they receive
PrimeCActive comparator2 tablets of PrimeC administered twice daily (4 tablets a day), at a daily dose of 1496 mg
Receives: Drug: PrimeC
PlaceboPlacebo comparator2 tablets of Placebo administered twice daily (4 tablets a day). Placebo tablets are matched in size, color and taste.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 6 months

  2. Number of subjects who discontinued treatment prematurely

    Number of subjects whose treatment is stopped prematurely for any reason

    Measured: 6 months

  3. Number of patients who discontinued treatment prematurely due to adverse events

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

    Measured: 6 months

  4. Number of patients with clinically significant abnormal laboratory values

    Measured: 6 months

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

    Measured: 6 months

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

    Measured: 6 months

Secondary outcomes (8)

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

    Measured: 6 months

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

    Measured: 6 months

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

    Measured: 6 months

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

    Measured: 6 months

  5. Survival at 6 months of treatment

    Overall Survival defined as time to death from any cause at 6 months of treatment

    Measured: 6 months

  6. Composite survival at 6 months of treatment

    Composite of overall survival, defined as time to death from any cause, or respiratory insufficiency (defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days) at 6 months of treatment

    Measured: 6 months

  7. Composite survival at 6 months of treatment

    Composite of overall survival, defined as time to death from any cause, or respiratory insufficiency (defined as tracheostomy or the use of non-invasive ventilation for ≥22 h per day for ≥10 consecutive days), or time to hospitalization due to ALS-related complications at 6 months of treatment

    Measured: 6 months

  8. Joint Assessment of Function and Survival after 6 months of treatment

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2022
  2. Study start31 May 2022
  3. Primary completion2 Nov 2023
  4. Study completion4 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05357950
Sponsor's protocol ID
NST003
Acronym
PARADIGM
Status last verified
Jul 2025
First submitted
27 Apr 2022
Last updated
5 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Cudkowicz M, Drory VE, Chio A, Lunetta C, Shoesmith C, van Eijk RPA, Salomon-Zimri S, Shtossel D, Kerem N, Shapira G, Shomron N, Russek-Blum N, Tracik F, Rosenfeld J, Shefner J. Safety and Efficacy of PrimeC in Amyotrophic Lateral Sclerosis: The PARADIGM Randomized Clinical Trial. JAMA Neurol. 2026 May 1;83(5):471-480. doi: 10.1001/jamaneurol.2026.0230.

    PubMed 41837970

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PrimeC in people with Amyotrophic Lateral Sclerosis and ALS, run by NeuroSense Therapeutics Ltd. at 4 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy, Canada, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of treatment-emergent adverse events (TEAEs) (time frame: 6 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05357950, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2025.

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