On Jul. 1, 2020, MediciNova announced that the Investigational New Drug Application (IND) for MN-166 (ibudilast) for prevention of Acute Respiratory Distress Syndrome (ARDS) has been accepted and is now open with the U.S. Food and Drug Administration (FDA). MediciNova was informed by the FDA that the proposed clinical investigation of MN-166 (ibudilast) for the prevention of ARDS in patients with COVID-19 may proceed.

Based on review and discussion with FDA, the design of the Phase 2 clinical trial includes the following elements:

• Randomized (1:1), double-blind, placebo-controlled, parallel group study in hospitalized COVID-19 patients at risk for developing ARDS and receiving standard-of-care including anticoagulation therapy.
• Subjects will be randomly assigned to receive up to 100 mg/day MN-166 or matching placebo for 7 days;
  • Patients will be followed up at Days 14 and 28;
  • The co-primary objectives include the proportion of subjects free of respiratory failure, subjects’ change in clinical status measured by NIAID scale, and plasma cytokine levels after 7 days of treatment;
  • Secondary objectives include safety, tolerability, and the proportion of subjects free of respiratory failure on Day 14.

Major inclusion criteria for trial eligibility will include confirmed SARS-CoV-2 infection, oxygen saturation (SpO₂) ≤92% on room air, chest imaging with abnormalities consistent with COVID-19 pneumonia, and has at least one risk factor that poses a higher risk for more severe illness from COVID-19.

Acute respiratory distress syndrome (ARDS) is a frequently lethal lung condition caused by excessive inflammation for which there are no effective therapies beyond supportive care. Normally, the lung exchanges oxygen for carbon dioxide in small airway sacs called alveoli. In ARDS, there is extensive inflammation and tissue injury in the alveoli of the lungs, and loss of the surfactant, a substance necessary for keeping alveoli open. These changes prevent the lungs from filling properly with air and providing the body with enough oxygen, causing life-threatening difficulty breathing. ARDS may develop over a few days, or it can get worse very quickly. The first symptom of ARDS is usually shortness of breath. Other signs and symptoms of ARDS are low blood oxygen, shallow, and/or rapid breathing. Infections are the most common cause of ARDS. These infections may include the flu, coronavirus, other viruses, and sepsis. The rate of death in the hospital is approximately 40% for ARDS patients.

MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterases (PDE) 4 and 10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in substance use disorders, neurodegenerative diseases (e.g., ALS and progressive MS), and chronic neuropathic pain.  MediciNova is developing MN-166 for various neurological conditions such as progressive MS, ALS and substance abuse/addiction.