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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: MN-166
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, MN-166, ibudilast, amyotrophic lateral sclerosis