Efficacy, Safety, Tolerability, and Biomarkers of Ibudilast (MN-166) in Patients Hospitalized With COVID-19 at Risk for ARDS

The goal of this study is to evaluate the effects of Ibudilast (MN-166) versus placebo in hospitalized patients infected with COVID-19 at risk for developing acute respiratory distress syndrome (ARDS) receiving standard of care (including anticoagulation therapy) by measuring the following outcomes: 1) the need for oxygen therapy at Days 7, 14, and 28, 2) clinical status as measured by the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale at Days 7, 14, and 28, and 3) safety (as measured by incidence of adverse events and clinical laboratory findings) and tolerability of Ibudilast.

This is a randomized (1:1) double-blind, placebo-controlled, parallel-group study evaluating the efficacy of Ibudilast to prevent ARDS in hospitalized patients infected with COVID-19 who are at risk for developing ARDS. The study will consist of a Screening Phase, Double-Blind Treatment Phase, and Follow-up Phase. Following the Screening Phase, if the participant meets eligibility criteria, they will be randomly assigned to Ibudilast or matching placebo. Participants will receive Ibudilast 100 mg/d (50 mg twice a day) or placebo every day for 7 days. Upon completion of the 7-day Treatment Phase, subject will be followed-up at Day 14 and at Day 28. Participants discharged prior to Day 7 will be given the remainder of their study medication (Ibudilast or placebo) to be taken at home twice daily until Day 7 and will be given a pulse oximeter to measure their oxygen levels once daily until Day 14.

The following screening assessments will be performed upon signing the Informed Consent Form (ICF): inclusion/exclusion criteria review, physical exam, vital signs and oxygen use, clinical status using the NIAID ordinal scale, 12-lead ECG, blood collection for plasma biomarkers. A complete blood count (CBC), comprehensive metabolic panel (CMP), D-dimer and coagulation tests will also be drawn. A serum pregnancy test will be given to pre-menopausal female participants. Concomitant medications taken within the last 7 days prior to study drug administration will be recorded.

During the Treatment Phase, hospitalized participants will be treated with Ibudilast or placebo for a 7-day period plus standard of care and anticoagulation therapy. During the Treatment Phase, participants will undergo study-related procedures including physical exam, ECG, oxygen use assessment, biomarkers and pharmacokinetic sample draws, CBC, CMP, D-dimer blood collection, clinical status using the NIAID scale, and information on adverse events and concomitant medications will be recorded.

On Study Day 14, conduct physical examination, clinical status, vital signs and oxygen use, ECG, CBC, CMP, D-dimer, and coagulation tests, biomarkers, AE and concomitant medications review. On Day 28, participant's clinical status and survival status will be recorded.

If the participant is discharged before Day 7, they will be given the remainder of their study drug to take at home for up to 7 days, and the Sponsor will supply a pulse oximeter to participants to measure their oxygen levels once daily until Day 14.

Eligibility Criteria:
Inclusion Criteria:

* SARS-CoV-2 infection confirmed with WHO criteria (including a positive PCR of any specimen, e.g., blood, respiratory, stool, urine, or any other body fluid)
* Chest imaging (radiograph, computerized tomography (CT) scan or lung ultrasound) with abnormalities consistent with COVID-19 pneumonia
* Oxygen saturation (SpO2) ≤92% on room air (RA), respiratory rate ≥24 breaths per min on RA, and/or requirement for supplemental oxygen
* At least 1 risk factor which may put patient at higher risk for more severe illness from COVID-19: Age \> 65, underlying serious heart disease, chronic lung disease, moderate to severe asthma, body mass index of ≥40, or diabetes

Exclusion Criteria:

* Suspected active bacterial, fungal, viral, or other cause of respiratory failure other than COVID-19
* Subject is already intubated and on ventilator support
* Known or suspected immunosuppression with immunosuppressant medications or chemotherapeutic agents
* Patient is receiving dialysis treatment
* On a home ventilator support or continuous domiciliary oxygen therapy for baseline lung disease
* Active tuberculosis infection