Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. The nerves lose the ability to trigger specific muscles, which causes the muscles to become weak. As a result, ALS affects voluntary movement and patients in the later stages of the disease may become totally paralyzed. Life expectancy of an ALS patient is usually 2-5 years. According to the ALS Association, there are approximately 20,000 ALS patients in the U.S. and approximately 6,000 people in the U.S. are diagnosed with ALS each year. Riluzole is the only pharmaceutical treatment approved for ALS, but it has limited efficacy.
Completed Clinical Trial of MN-166 in ALS
In August 2014, MediciNova announced FDA approval to initiate a clinical trial of MN-166 (ibudilast) in amyotrophic lateral sclerosis (ALS). The trial was a randomized, double-blind, placebo-controlled study which included a six-month treatment period followed by a six-month open-label extension. The study evaluated several efficacy endpoints including functional activity (ALSFRS-R), respiratory function, muscle strength, and non-invasive ventilation (NIV) utilization in addition to monitoring the safety and tolerability of MN-166 60 mg/day versus placebo when administered in combination with riluzole in subjects with ALS. Subject enrollment in this trial began in early October 2014 and top-line results were announced in December 2017. This clinical trial is completed and there will be no additional enrollment of patients.
The principal investigator of the study was Benjamin Rix Brooks, MD, Director, Carolinas Neuromuscular/ALS-MDA Center at Carolinas HealthCare System Neurosciences Institute in Charlotte, NC. The study was funded by MediciNova with the support of Carolinas HealthCare System. Dr. Benjamin Rix Brooks, principal investigator, commented, “We are excited to initiate this study of ibudilast which targets a disease with limited treatment options. Ibudilast has demonstrated attenuating effects on activated glia cells which are considered to play a key role in disease progression in ALS patients.”
In October 2014, MediciNova announced that the U.S. CDC’s National ALS Registry Research Committee voted to approve support of patient recruitment for MediciNova’s clinical trial of MN-166 (ibudilast) in amyotrophic lateral sclerosis (ALS). CDC has notified ALS patients who are registered with the CDC’s National ALS Registry and who also met the inclusion criteria about the initiation of MediciNova’s clinical trial of MN-166 (ibudilast) in ALS.
About the ALS Trial
This was a single center, randomized, double-blind, placebo-controlled, 6-month study designed to evaluate the safety, tolerability and clinical endpoint responsiveness of MN-166 (60 mg/day) when administered as an adjunct to riluzole (100 mg/day) in subjects with amyotrophic lateral sclerosis (ALS). This study consisted of two treatment arms, MN-166 and matching placebo, and randomization was in a 2:1 ratio (MN-166: placebo). To be eligible, subjects must have had a diagnosis of sporadic or familial ALS with onset of less than 3 years from first clinical weakness prior to screening and must be on a stable dose of riluzole for at least 1 month prior to study drug treatment.
Upon completion of the Double-blind Phase, subjects randomized to the placebo arm continued for an additional 6 months and received open-label MN-166. As there were no safety or tolerability concerns in the MN-166 treated group, a decision was made to extend participation to the MN-166 treated group into the Open-Label Extension (OLE) Phase.
The primary objective was to evaluate the safety and tolerability of MN-166 60 mg/day versus placebo when administered for 6 months with riluzole in subjects with ALS. The secondary objective is to evaluate the clinical endpoint responsiveness of MN-166 60 mg/day versus placebo when administered with riluzole in subjects with amyotrophic lateral sclerosis as measured by the following assessments:
- Functional activity as assessed by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R)
- Respiratory function as measured by slow vital capacity (SVC), Maximum Inspiratory Pressure (MIP) also known as Negative Inspiratory Force (NIF) and Forced Expiratory Volume in 1 second (FEV1) measured under SVC protocol
- Muscle strength measured by manual muscle testing (MMT) and instrumented hand grip dynamometry
- Non-invasive ventilation (NIV) utilization measured by clinically indicated prescription for NIV intervention and time to clinically indicated prescription for NIV intervention in each group
For more information on the MN-166 (ibudilast) clinical trial in ALS, please visit https://clinicaltrials.gov/ct2/show/NCT02238626?intr=ibudilast&rank=9.