Enoxacin for Amyotrophic Lateral Sclerosis (ALS)

NCT04840823 | Completed Phase 1

• 1 other identifier: REALS-1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the safety of the drug enoxacin at specific dose levels in adults with ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Enoxacin

Outcome Measures

Primary Outcomes (6)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  The incidence of adverse events (new or worsened from baseline (where baseline refers to those AEs recorded prior to dosing on day 1 of dosing)) will be summarized by primary system organ class and preferred term as frequency count and percentage of participants with AEs.

  From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

• Incidence of abnormalities in clinical laboratory assessments

  Clinical laboratory data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

• Incidence of abnormalities in vital signs

  Vital sign data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

• Incidence of abnormalities in physical and neurological examinations

  Physical and neurological examinations will be characterized by abnormalities and in changes from baseline, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

• Incidence of abnormalities in electrocardiograms (ECGs)

  ECG data will be characterized by abnormalities in values and in changes from baseline values, where baseline refers to measurements taken prior to dosing on day 1 of dosing.

  From baseline (prior to dosing on day 1 of dosing) to 14 day +/- 2 day follow up visit

• Ability of participants to remain on their assigned dose for the full 30 day treatment period

  The ability of participants to remain on each dose level will be measured by the mean number of missed doses.

  From the beginning (day 1) to the end (day 30) of the 30 day treatment period

Secondary Outcomes (10)

• Maximum plasma concentration (Cmax) of enoxacin after administration on day 1 and 30

  Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

• Time of maximum plasma concentration (Tmax) of enoxacin after administration on day 1 and 30

  Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

• Area under the plasma concentration-time curve from time zero until the time corresponding with the last observed quantifiable concentration (AUC 0-last) of enoxacin after administration on day 1 and 30

  Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

• Area under the plasma concentration-time curve extrapolated to infinity (AUC 0-inf) of enoxacin after administration on day 1 and 30

  Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

• Terminal half-life (t1/2) of enoxacin after administration on day 1 and 30

  Prior to dosing and at 1, 2, 4, 6, 8 and 24 hours post morning dosing on days 1 and 30 of dosing.

Other Outcomes (1)

• Ability of enoxacin to modulate the expression of one or more miRNA species in cerebrospinal fluid (CSF) and/or plasma

  Blood: prior to morning dosing on days 1, 7 (+/- 2 days), 14 (+/- 2 days), 21 (+/- 2 days) and 30, and at the 14 day +/- 2 day follow-up visit. CSF: prior to dosing on day 1, and 2 hours (+/-1 hour) post dosing on day 30.

Study Arms (3)

Enoxacin 200mg twice daily

EXPERIMENTAL

Enoxacin 200mg twice daily (one dose in the morning and one dose in the evening) for 30 days, except day 1 and day 30 when only the morning dose will be taken. Participants will take 1 active 200mg enoxacin tablet and 2 placebo tablets per dose.

Drug: Enoxacin; Drug: Placebo

Enoxacin 400mg twice daily

EXPERIMENTAL

Enoxacin 400mg twice daily (one dose in the morning and one dose in the evening) for 30 days, except day 1 and day 30 when only the morning dose will be taken. Participants will take 2 active 200mg enoxacin tablets and 1 placebo tablet per dose.

Drug: Enoxacin; Drug: Placebo

Enoxacin 600mg twice daily

EXPERIMENTAL

Enoxacin 600mg twice daily (one dose in the morning and one dose in the evening) for 30 days, except day 1 and day 30 when only the morning dose will be taken. Participants will take 3 active 200mg enoxacin tablets per dose.

Drug: Enoxacin

Interventions

Enoxacin DRUG

Oral 200mg tablet

Enoxacin 200mg twice daily; Enoxacin 400mg twice daily; Enoxacin 600mg twice daily

Placebo DRUG

Oral tablet

Enoxacin 200mg twice daily; Enoxacin 400mg twice daily

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of familial or sporadic ALS
• FVC of ≥ 50 percent predicted
• If female, is not breastfeeding and is not pregnant
• Has been on a stable dose of riluzole, or has not taken riluzole, for at least 30 days prior to screening
• If taking concomitant edaravone at study entry, must have completed at least one cycle of edaravone therapy prior to screening
• Not currently taking and has not taken for at least 30 days prior to screening any Theophylline containing medications, clozapine, or duloxetine
• No active infection in the 30 days prior to randomization
• Has not taken any fluoroquinolone antibiotics for at least 30 days prior to screening

You may not qualify if:

• Hypersensitivity/allergy to fluoroquinolones
• Diagnosed with another neurodegenerative disease
• Significant pulmonary disorder not attributed to ALS, central nervous system disorder associated with seizures, myasthenia gravis, active rheumatologic disease, tendinopathy, or any severe uncontrolled medical condition (other than ALS)
• Severe renal impairment or impaired liver function
• Baseline prolongation of QT interval/corrected QT interval (QTc) at screening, treatment with any agent that may prolong Qt/QTc interval, or history of any other at-risk other cardiac condition
• Currently enrolled in another clinical trial involving an experimental drug or device

Sponsors & Collaborators

• McGill University: lead
• Weizmann Institute of Science: collaborator
• Apotex Inc.: collaborator

Study Sites (1)

Montreal Neurological Institute-Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Related Publications (3)

• Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills AM, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R Jr, Chen A, Hornstein E. miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13111-6. doi: 10.1073/pnas.1006151107. Epub 2010 Jun 29.

  PMID: 20616011 BACKGROUND

• Emde A, Eitan C, Liou LL, Libby RT, Rivkin N, Magen I, Reichenstein I, Oppenheim H, Eilam R, Silvestroni A, Alajajian B, Ben-Dov IZ, Aebischer J, Savidor A, Levin Y, Sons R, Hammond SM, Ravits JM, Moller T, Hornstein E. Dysregulated miRNA biogenesis downstream of cellular stress and ALS-causing mutations: a new mechanism for ALS. EMBO J. 2015 Nov 3;34(21):2633-51. doi: 10.15252/embj.201490493. Epub 2015 Sep 1.

  PMID: 26330466 BACKGROUND

• Reichenstein I, Eitan C, Diaz-Garcia S, Haim G, Magen I, Siany A, Hoye ML, Rivkin N, Olender T, Toth B, Ravid R, Mandelbaum AD, Yanowski E, Liang J, Rymer JK, Levy R, Beck G, Ainbinder E, Farhan SMK, Lennox KA, Bode NM, Behlke MA, Moller T, Saxena S, Moreno CAM, Costaguta G, van Eijk KR, Phatnani H, Al-Chalabi A, Basak AN, van den Berg LH, Hardiman O, Landers JE, Mora JS, Morrison KE, Shaw PJ, Veldink JH, Pfaff SL, Yizhar O, Gross C, Brown RH Jr, Ravits JM, Harms MB, Miller TM, Hornstein E. Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology. Sci Transl Med. 2019 Dec 18;11(523):eaav5264. doi: 10.1126/scitranslmed.aav5264.

  PMID: 31852800 BACKGROUND

Related Links

• Clinical Research Unit at The Montreal Neurological Institute-Hospital, McGill University

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Enoxacin

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Angela Genge, MD, FRCP

  McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurologist, Neurology and Neurosurgery

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 12, 2021
• Study Start: March 26, 2021
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)