Amyotrophic lateral sclerosis (ALS) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: PrimeC
Product Code: [N/A]
Pharmaceutical Form: Tablet
INN or Proposed INN: CIPROFLOXACINA CLORIDRATO
CAS Number: 8639-32-0
Current Sponsor code: NA
Other descriptive name: Cipro, Ciprof
Sponsors
NeuroSense Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to comprehend and willing to sign an informed consent form (ICF) 2. Males or females between the ages of 18 and 75 years of age, inclusive 3. 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) 4. Disease duration after first symptom (muscle weakness) less than 30 months prior to screening 5. Pre-enrollment ALSFRS-R slope from disease onset => 0.3 points per month 6. ALSFRS-R at screening = >25 7. Item 3 (swallowing) in ALSFRS-R => 3 8. 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 9. Upright slow vital capacity (SVC) = >60% of predicted for age, height, weight and sex at screening according to the GLI-2012 10. 18 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 69 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A past history of adverse reaction/hypersensitivity to either NSAIDs, celecoxib or fluoroquinolones, ciprofloxacin 2. Any known clinically significant abnormal gastric mucosal erosion, ulcer or tumor or/and GI disorder and/or bariatric surgery 3. Known history of clinically significant impairment of renal function (creatinine => 1.5) 4. 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 5. 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 6. Known or suspected diagnosis or family history of epilepsy in first degree relatives 7. Known predisposition to tendinitis 8. Known or suspected to be a poor CYP2C9 metabolizer 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 9. Tracheostomy or percutaneous gastrostomy use 10. 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: a. 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 b. NYHA Class II or greater congestive heart failure c. Chronic obstructive pulmonary disease or asthma requiring daily use of bronchodilator medications d. Poorly controlled or brittle diabetes mellitus e. 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 11. Subject who is treated with chronic aspirin or NSAIDs and is at risk if stopped. Clopidogrel is allowed and can replace Aspirin. 12. Any contraindication for ciprofloxacin and celecoxib according to the current prescribing information. 13. Female who is pregnant or breastfeeding or with intention of becoming pregnant during the course of the study 14. Any impairment or social circumstance that, in the opinion of the Investigator, would render the subject not suitable to participate in the study 15. Subject, or subject's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study 16. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the trial is to assess the safety and tolerability of PrimeC treatment versus placebo in subject with ALS and to assess the efficacy of PrimeC treatment versus placebo in subjects with ALS.;Secondary Objective: Change from baseline to 6 months in ALS functional rating scale-revised, change from baseline to 6 months in slow vital capacity, change from baseline to 6 months in quality of life ALSSQOL-SF, change from base to 6 months in PROMIS-10 quality of life questionnaire, overall survival defined as time to death from an cause 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 greater than or equal to 22h per day for greater than or equal to 10 consecutive days 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, Joint Assessment of Function and Survival after 6 months of treatment;Primary end point(s): Primary safety and tolerability endpoints: •Incidence and severity of treatment-emergent adverse events (TEAEs) •Number (%) of subjects who discontinued treatment prematurely •Number (%) of subjects who discontinued treatment prematurely due to AEs •Number (%) of subjects with clinically significant abnormal laboratory values following treatment Primary efficacy endpoints: •The mean difference between PrimeC and Placebo in serum concentration of NDE TDP-43 at month 6 •The mean difference between PrimeC and placebo in serum concentration of NDE PgJ2 at month 6 ;Timepoint(s) of evaluation of this end point: Primary outcomes, assessing biological activity, will be evaluated by analyzing the levels of two key neuron-derived exosom | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline to 6 months in ALS functional rating scale – revised (ALSFRS-R) - Change from baseline to 6 months in slow vital capacity (SVC) - Change from baseline to 6 months in quality-of-life ALSSQOL-SF - Change from baseline to 6 months in PROMIS-10 quality of life questionnaire - Overall Survival defined as time to death from any cause 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 - 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 ospitalization due to ALS- related complications at 6 months of treatment - Joint Assessment of Function and Survival after 6 months of treatment;Timepoint(s) of evaluation of this end point: The ALSFRS-R will be performed at each study visit . Pulmonary function assessment will be performed at each study visit The ALSSQOL-SF and the PROMIS-10 (PROMIS Scale v1.2 – Global Health) questionnaire will be performed at baseline and 6-month visits Overall survival defined as time to death from any cause at end of study. | — |
Countries
Israel, Italy, United States
Contacts
Public ContactDiana Shtossel
NeuroSense Therapeutics Ltd.
Outcome results
None listed