Evaluation of MN-166 (Ibudilast) for 12 Months Followed by an Open-label Extension for 6 Months in Patients With ALS
- Registration Number
- NCT04057898
- Lead Sponsor
- MediciNova
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 230
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo placebo Subjects will take up to 5 matching placebo capsules twice a day for 12 months. MN-166 MN-166 Subjects will take MN-166 10 mg capsules, up to 50 mg twice a day for 12 months.
- Primary Outcome Measures
Name Time Method Change from baseline in ALSFRS-R score at Month 12 (or last measurement before death in case of censoring) and survival time. 12 months 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.
- Secondary Outcome Measures
Name Time Method Mean change from baseline of functional activity measured by ALSFRS-R at Month 12 12 months 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.
Responders, measured in percent of subjects overall, whose ALSFRS-R total score was stable or improved 12 months Proportion of subjects in which ALSFRS-R total score was stable or improved.
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 12 months 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.
Changes from Baseline in Laboratory Values 12 months Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.
Mean change from baseline of muscle strength measured by hand-held dynamometry Baseline, Treatment Phase Week 6, Months 3, 6, 9 and12 time points. 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.
Time to survival 12 months Defined by death or permanent dependency to ventilator or tracheostomy.
Mean change from baseline on quality of life assessed by ALSAQ-5 at Month 12 12 months 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.
Trial Locations
- Locations (16)
University of California
🇺🇸Orange, California, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Indiana University IU Health Neuroscience Center
🇺🇸Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Hennepin Healthcare Research Institute
🇺🇸Minneapolis, Minnesota, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
McMaster University Medical Center
🇨🇦Hamilton, Ontario, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Montreal Neurological Institute and Hospital
🇨🇦Montreal, Quebec, Canada
University of Saskatchewan - Sastakoon Hospital
🇨🇦Saskatoon, Saskatchwean, Canada
Hopital de L'Enfant-Jesus, CHU de Quebec-Universite Laval
🇨🇦Quebec, Canada