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

Amyotrophic Lateral Sclerosis Clinical Trial

— COMBAT-ALS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04057898
• Other study ID #: MN-166-ALS-2301
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 28, 2020
• Est. completion date: December 2026

Study information

• Verified date: June 2024
• Source: MediciNova
• Contact: Project Management Team
• Phone: 858-373-1500
• Email: clinicaltrialinfo[@]medicinova.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• MN-166
Subjects will take MN-166 for 12 months followed by a 6-month open-label extension phase.
• placebo
Subjects will take matching placebo for 12 months followed by a 6-month open-label extension phase.

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	McMaster University Medical Center	Hamilton	Ontario
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Hopital de L'Enfant-Jesus, CHU de Quebec-Universite Laval	Quebec
Canada	University of Saskatchewan - Sastakoon Hospital	Saskatoon	Saskatchwean
Canada	Clinique Maladies Neuromusculaire	Sherbrooke	Quebec
Canada	Sunnybrook Research Institute	Toronto	Ontario
United States	Lehigh Valley Health Network	Allentown	Pennsylvania
United States	Augusta University	Augusta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Duke University	Durham	North Carolina
United States	Indiana University IU Health Neuroscience Center	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	Hennepin Healthcare Research Institute	Minneapolis	Minnesota
United States	University of California	Orange	California
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
MediciNova

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to survival	Defined by death or permanent dependency to ventilator or tracheostomy.	12 months
Secondary	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
Secondary	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

External Links

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