Clinical trial NCT04057898: Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
MN-166
ibudilast
amyotrophic lateral sclerosis
Lead sponsor: MediciNova
Sponsor class: INDUSTRY
First posted: 2019-08-15
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in ALSFRS-R score at Month 12 (or last measurement before death in case of censoring) and survival time.
timeFrame: 12 months
Secondary outcomes:
measure: Mean change from baseline of muscle strength measured by hand-held dynamometry
timeFrame: Baseline, Treatment Phase Week 6, Months 3, 6, 9 and12 time points.
measure: Mean change from baseline on quality of life assessed by ALSAQ-5 at Month 12
timeFrame: 12 months
measure: Mean change from baseline of functional activity measured by ALSFRS-R at Month 12
timeFrame: 12 months
measure: Responders, measured in percent of subjects overall, whose ALSFRS-R total score was stable or improved
timeFrame: 12 months
measure: Time to survival
timeFrame: 12 months
measure: Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: 12 months
measure: Changes from Baseline in Laboratory Values
timeFrame: 12 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University IU Health Neuroscience Center
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: Hennepin Healthcare Research Institute
state: Minnesota
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan - Sastakoon Hospital
state: Saskatchwean
city: Quebec
country: Canada
facility: Hopital de L'Enfant-Jesus, CHU de Quebec-Universite Laval
Study officials:
affiliation: Medicinova Inc
name: Project Management Team
role: STUDY_CHAIR
References:
citation: 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.