Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With ALS (COMBAT-ALS)

A Phase 2b/3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 12 Month Clinical Trial to Evaluate the Efficacy and Safety of MN-166 (Ibudilast) Followed by Open-Label Extension Phase in Subjects With Amyotrophic Lateral Sclerosis

A Phase 2b/3 multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety and tolerability of MN-166 given to ALS participants for 12 months followed by a 6-month open-label extension phase.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: MN-166; Drug: placebo

Detailed Description

This is a Phase 2b/3 multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety and tolerability of MN-166 followed by an open-label extension phase compared to matching placebo in subjects diagnosed with ALS.

The study will consist of a screening phase (up to 30 days) followed by a double-blind phase (12 months). Following the screening phase, subjects who continue to meet entry criteria will be randomly assigned to one of two treatment groups: MN-166 or matching placebo in a 1:1 ratio. Upon completion of the double-blind phase, subjects will be given the option to continue to the Open-label Extension Phase for a period of six months.

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1J 1Z4
    • Hopital de L'Enfant-Jesus, CHU de Quebec-Universite Laval
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
  • Saskatchwean
    • Saskatoon, Saskatchwean, Canada, S7K 0M7
      • University of Saskatchewan - Sastakoon Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • University of California
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University IU Health Neuroscience Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare Research Institute
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

• Male or female subjects age 18 - 80 years, inclusive;
• Diagnosis of familial or sporadic ALS as defined by the El Escorial-Revised (2000) research diagnostic criteria for ALS [clinically definite, clinically probable, probable-laboratory-supported];
• ALS onset of ≤18 months from first clinical signs of weakness prior to screening;
• If currently using riluzole, subject must be on a stable dose for at least 30 days prior to initiation of study drug;
• If currently using edaravone, subject should have completed at least 14 days of their initial treatment cycle prior to initiation of study drug;
• Last documented pulmonary function test result (i.e., slow vital capacity or forced vital capacity) must be greater than or equal to 70% predicted;
• Able to swallow study medication capsules;
• No known allergies to the study drug or its excipients;
• Received pneumococcal vaccine within 6 years prior to starting clinical trial.

Major Exclusion Criteria:

• Confirmed hepatic insufficiency or abnormal liver function (AST and/or ALT >3 times upper limit of normal);
• Currently diagnosed with a clinically significant psychiatric disorder or dementia that would preclude evaluation of symptoms;
• Currently use or treated with parenteral (intramuscular or intravenous) high dose (>25 mg/week) Vitamin B12 within 30 days prior to study drug administration;
• Poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator;
• Currently participating, or has participated in a study with an investigational or marketed compound or device within 30 days or 5 half-lives, whichever is shorter, prior to signing the informed consent;
• Use of tracheostomy or >22/24-hour ventilatory support.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MN-166; Subjects will take MN-166 10 mg capsules, up to 50 mg twice a day for 12 months.	Drug: MN-166; Subjects will take MN-166 for 12 months followed by a 6-month open-label extension phase.; Other Names: ibudilast
Placebo Comparator: placebo; Subjects will take up to 5 matching placebo capsules twice a day for 12 months.	Drug: placebo; Subjects will take matching placebo for 12 months followed by a 6-month open-label extension phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ALSFRS-R score at Month 12 (or last measurement before death in case of censoring) and survival time.	The amyotrophic lateral sclerosis functional rating scale-revised, or ALSFRS-R, measures the functional status of subjects with ALS. It is based on 12 items, each of which is rated on a 5-point scale (0 to 4). The rate of total functional disability thus ranges from 0 (maximum disability) to 48 (normal function) points.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline of muscle strength measured by hand-held dynamometry	Hand-held dynamometry, or HHD, is used to measure the force generated by each muscle. The scale ranges from 0 (no visible movement of the part) to 10 (holds test position against strong pressure). Thus, the higher the total score, the higher muscle strength is observed.	Baseline, Treatment Phase Week 6, Months 3, 6, 9 and12 time points.
Mean change from baseline on quality of life assessed by ALSAQ-5 at Month 12	The Amyotrophic Lateral Sclerosis Assessment Questionnaire, or ALSAQ-5, is a patient self-report questionnaire specifically designed to measure 5 areas of health: physical mobility, activities of daily living and independence, eating and drinking, communication and emotional functioning. The subject is asked about 5 different areas of difficulties in their daily lives: ability to stand up, use of limbs, consuming solid food, level of speech coherence, and degree of hope about the future.Each question provides 5 choices from which to choose: Never, Rarely, Sometimes, Often, and Always or cannot do at all.	12 months
Mean change from baseline of functional activity measured by ALSFRS-R at Month 12	The ALSFRS-R assessment tool measures the functional status of subjects with ALS. It is based on 12 items, each of which is rated on a 5-point scale (0 to 4). The rate of total functional disability thus ranges from 0 (maximum disability) to 48 (normal function) points. In this context, the ALSFRS-R total score change (lower, same, higher) is documented.	12 months
Responders, measured in percent of subjects overall, whose ALSFRS-R total score was stable or improved	Proportion of subjects in which ALSFRS-R total score was stable or improved.	12 months
Time to survival	Defined by death or permanent dependency to ventilator or tracheostomy.	12 months
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0	The incidence of treatment-emergent adverse events (TEAEs), severity (mild, moderate, severe), as well as relationship to study treatment (not related, possibly related, probably related) and whether they are considered serious.	12 months
Changes from Baseline in Laboratory Values	Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.	12 months

Collaborators and Investigators

• Sponsor: MediciNova
• Investigators: Study Chair: Project Management Team, Medicinova Inc

Publications and helpful links

General Publications

• Oskarsson B, Maragakis N, Bedlack RS, Goyal N, Meyer JA, Genge A, Bodkin C, Maiser S, Staff N, Zinman L, Olney N, Turnbull J, Brooks BR, Klonowski E, Makhay M, Yasui S, Matsuda K. MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. Neurodegener Dis Manag. 2021 Dec;11(6):431-443. doi: 10.2217/nmt-2021-0042. Epub 2021 Nov 24.
• Trist BG, Fifita JA, Hogan A, Grima N, Smith B, Troakes C, Vance C, Shaw C, Al-Sarraj S, Blair IP, Double KL. Co-deposition of SOD1, TDP-43 and p62 proteinopathies in ALS: evidence for multifaceted pathways underlying neurodegeneration. Acta Neuropathol Commun. 2022 Aug 25;10(1):122. doi: 10.1186/s40478-022-01421-9.

Helpful Links

• This webinar explains the COMBAT-ALS study design and background of MN-166 (ibudilast) as a potential treatment for ALS.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2020
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ALS; amyotrophic lateral sclerosis; ibudilast; MN-166
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Substandard Drugs; Pharmaceutical Preparations; ibudilast
• Other Study ID Numbers: MN-166-ALS-2301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No