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

Sponsor

MediciNova (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04429555

Collaborator

(none)

Enrollment

Locations

Arms

22.6

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aims to evaluate MN-166 (ibudilast) in patients with COVID-19 who are at risk of developing acute respiratory distress syndrome. Subjects will be screened, randomly assigned to MN-166 or placebo groups, receive study drug on Days 1-7, and followed up on Day 14 and Day 28.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Viral	Drug: Ibudilast Drug: Placebo	Phase 2

Detailed Description

This is a randomized (1:1) double-blind, placebo-controlled, parallel-group study of ibudilast in hospitalized COVID-19 subjects at risk for developing ARDS receiving standard of care including anticoagulation. The study will consist of a Screening Phase followed by a Treatment and Follow-up Phase. Following the Screening Phase, if the subject meets eligibility criteria, subject will be administered treatment with MN-166 (ibudilast) or placebo. Subjects will receive ibudilast 100 mg/d (50 mg b.i.d) 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 post baseline. Subjects discharged prior to Day 7 will be given the remainder of their study medication to be taken at home twice daily 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 ICF:

inclusion/exclusion criteria review, physical exam, assess vital signs and O2 use, clinical status using the National Institute of Allergy and Infectious Diseases scale, 12-lead ECG, draw blood for plasma biomarkers that include: migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNFα), and C-reactive protein (CRP). A complete blood count (CBC), comprehensive metabolic panel (CMP), D-dimer and coagulation tests will also be drawn. A serum pregnancy test will be done in pre-menopausal females. Prior concomitant medications taken within the last 7 days prior to study drug administration will be recorded.

During the Treatment Phase, hospitalized subjects will be treated with MN-166 or placebo for a 7-day period. During the Treatment Phase, subjects will undergo study-related procedures including physical exam, ECG, Oxygen use assessment, biomarkers and pharmacokinetic samples draw, CBC, CMP, D-dimer blood collection, clinical assessment 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, subject's clinical status and survival status will be recorded.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlled, parallel-group study.Randomized, double-blind, placebo-controlled, parallel-group study.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, Tolerability, Biomarkers and Pharmacokinetics of Ibudilast (MN-166) in COVID-19 Subjects at Risk for Developing Acute Respiratory Distress Syndrome

Actual Study Start Date :

Jan 11, 2021

Actual Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MN-166 (ibudilast) MN-166 capsules, 50 mg twice daily, for 7 days.	Drug: Ibudilast Ibudilast orally administered, 50 mg twice daily for 7 days. Other Names: MN-166
Placebo Comparator: Placebo Placebo capsules, 50 mg twice daily, for 7 days.	Drug: Placebo Placebo orally administered, 50 mg twice daily for 7 days.

Arm

Intervention/Treatment

Experimental: MN-166 (ibudilast)

MN-166 capsules, 50 mg twice daily, for 7 days.

Drug: Ibudilast

Ibudilast orally administered, 50 mg twice daily for 7 days.

Other Names:

MN-166

Placebo Comparator: Placebo

Placebo capsules, 50 mg twice daily, for 7 days.

Drug: Placebo

Placebo orally administered, 50 mg twice daily for 7 days.

Outcome Measures

Primary Outcome Measures

Proportion of subjects free from respiratory failure [7 days]
Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7
Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7 [7 days]
Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Percentage of patients with improvement in clinical status [7 days]
Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.
Change in cytokine levels from baseline [7 days]
Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.

Secondary Outcome Measures

Adverse event Incidence, severity, relationship to study drug, and study discontinuations [Days 7, 14]
Incidence, frequency, and severity of adverse events at Day 7 and Day 14
Changes in laboratory values from baseline [7 days]
Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.
Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14 [14 days]
Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14
Mean change from baseline in clinical status [Days 14, 28]
Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28
Incidence of mechanical ventilation or intubation [Days 7, 14]
Proportion of subjects receiving mechanical ventilation or intubation.
Intensive care unit admission [7 days]
Proportion of subjects requiring submission to the intensive care unit
Plasma concentrations of Ibudilast [7 days]
Blood sample collection to determine plasma concentrations of ibudilast.
All cause mortality [Days 7, 14, 28]
Number of deaths from any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, CT scan or lung ultrasound) with abnormalities consistent with COVID-19 pneumonia
SpO2 ≤ 92% on room air (RA), RR ≥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
Subject is on dialysis
On home ventilator support or continuous domiciliary O2 therapy for baseline lung disease
Active tuberculosis (TB) infection