Open Label Study to Evaluate Ciprofloxacin/Celecoxib Combination in Patients With ALS

• ClinicalTrials.gov Identifier: NCT04165850
• Recruitment Status: Completed
• First Posted: November 18, 2019
• Last Update Posted: March 3, 2021
• Sponsor: NeuroSense Therapeutics Ltd.
• Information provided by (Responsible Party): NeuroSense Therapeutics Ltd.

Study Description

Brief Summary:

This is an open label, off label study, to provide interested ALS patients with Ciprofloxacin/Celecoxib fixed dose combination, while assessing safety and tolerability and routine disease progression measures (ALSFRS-R and Vital Capacity).

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis; ALS	Drug: Fixed dose combination Ciprofloxacin/Celecoxib	Phase 2

Detailed Description:

Patients will be prescribed a fixed dose combination of Ciprofloxacin and Celecoxib to be taken thrice daily, and will be monitored for safety and tolerability. Additionally, routine disease progression measures will be assessed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Ciprofloxacin/Celecoxib Combination in Patients With ALS
• Actual Study Start Date: November 25, 2019
• Actual Primary Completion Date: January 19, 2021
• Actual Study Completion Date: January 19, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fixed dose Ciprofloxacin and Celecoxib; Fixed dose Ciprofloxacin and Celecoxib capsule to be taken thrice daily, total dose 909mg/day	Drug: Fixed dose combination Ciprofloxacin/Celecoxib; Fixed dose Ciprofloxacin and Celecoxib capsule to be taken thrice daily, total dose 909mg/day; Other Name: PrimeC

Outcome Measures

Primary Outcome Measures :

1. Number of participants with one or more treatment-emergent adverse events [ Time Frame: 15 months ]
   Treatment emergent adverse event is any medical event associated with the drug
2. Number of patients who discontinued treatment prematurely [ Time Frame: 15 months ]
   Number of patients whose treatment is stopped prematurely for any reason
3. Number of patients who discontinued treatment prematurely due to adverse events [ Time Frame: 15 months ]
   Number of patients whose treatment is stopped prematurely specifically due to adverse events
4. Number of patients with significant abnormal laboratory values [ Time Frame: 15 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 World Federation of Neurology El Escorial criteria)
4. Disease duration after first symptom less than 3 years prior to baseline
5. Patients may be treated in parallel with Riluzole and/or Edaravone; 30 days of stable use prior to enrollment is required
6. Upright forced vital capacity (FVC) ≥ 50% of predicted for age, height, weight and sex at screening
7. Patient is able to swallow tablets/ capsules
8. A caregiver (if one is needed)
9. Female patients 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

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
3. Known history of clinically significant impairment of renal function (creatinine ≥ 1.5)
4. Known or suspected 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

7. Presence at screening of any medically significant cardiac, pulmonary, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety data, including, but not limited to:

   1. Mean systolic blood pressure >180 mm Hg; mean diastolic blood pressure >100 mm Hg (measurements taken after few min rest) that persist on 3 successive measurements taken at least 2 minutes apart
   2. NYHA Class II or greater congestive heart failure
   3. Chronic obstructive pulmonary disease or asthma requiring daily use of bronchodilator medications
   4. Poorly controlled or brittle diabetes mellitus
   5. Cognitive impairment, related to ALS or otherwise, sufficient to impair patient's ability to understand and/or comply with study procedures and provide informed consent
8. Patient who is treated with chronic aspirin or NSAIDs, and is at risk if stopped. Clopidogrel is allowed and can replace Aspirin.
9. Female who is pregnant or breastfeeding or with intention of becoming pregnant during the course of the study
10. Any impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study
11. Patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
12. Patient 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

Contacts and Locations

Locations

Israel

Sourasky Medical Center

Tel Aviv, Israel

Sponsors and Collaborators

NeuroSense Therapeutics Ltd.

Investigators

• Principal Investigator: Vivian Drory, MD; Sourasky Medical Center

More Information

• Responsible Party: NeuroSense Therapeutics Ltd.
• ClinicalTrials.gov Identifier: NCT04165850
• Other Study ID Numbers: NST002
• First Posted: November 18, 2019
• Last Update Posted: March 3, 2021
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Ciprofloxacin; Celecoxib; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents; Cytochrome P-450 CYP1A2 Inhibitors