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

Pneumonia, Viral Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04429555
• Other study ID #: MN-166-COVID-19-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 11, 2021
• Est. completion date: December 1, 2023

Study information

• Verified date: May 2023
• Source: MediciNova
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 1, 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• Pneumonia, Viral
• Respiratory Distress Syndrome

Intervention

Drug:
• Ibudilast
Ibudilast orally administered, 50 mg twice daily for 7 days.
• Placebo
Placebo orally administered, 50 mg twice daily for 7 days.

Locations

Country	Name	City	State
United States	Denver Health and Hospital Authority	Denver	Colorado
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
MediciNova

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects free from respiratory failure at Day 7	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. The scale is as follows: 1 = Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5=Hospitalized, Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8=Death.	Day 7
Primary	Proportion of subjects with at least a 1-point improvement in clinical status using the National Institute on Allergy and Infectious Disease 8-point ordinal scale and discharge record at Day 7	Percentage of subjects who improved at least by 1 point in the National Institute of Allergy and Infectious Diseases 8-point scale and discharge record at Day 7. The scale is as follows: 1 = Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5=Hospitalized, Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8=Death.	Day 7
Secondary	Adverse event incidence and severity	Incidence, frequency, and severity of adverse events	Days 7, 14, 28 and 60 (Day 60 applies to intubated subjects only)
Secondary	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 Days 14, 28, and 60	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 Days 14, 28, and 60 (Day 60 applies to intubated subjects only). The scale is as follows: 1 = Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5=Hospitalized, Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8=Death.	Days 14, 28, and 60 (Day 60 applies to intubated subjects only)
Secondary	Mean change from baseline in clinical status at Days 7, 14, 28, and 60	Mean change from baseline in clinical status at Days 7,14, 28, and 60 using the National Institute on Allergy and Infectious Disease 8-point ordinal scale and discharge record at Days 7, 14, 28, and 60 (Day 60 applies to intubated subjects only). The scale is as follows: 1 = Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5=Hospitalized, Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8=Death.	Days 7, 14, 28, and 60 (Day 60 applies to intubated subjects only)
Secondary	Incidence of mechanical ventilation or intubation at Day 7, 14, 28, and 60	Proportion of subjects receiving mechanical ventilation or intubation at Days 7, 14, 28, and 60	Days 7, 14, 28, and 60 (Day 60 applies to intubated subjects only)
Secondary	Proportion of subjects with at least a 1-point improvement in clinical status at Days 14, 28, and 60	Proportion of subjects with at least a 1-point improvement in clinical status at Days 14, 28, and 60 using the National Institute on Allergy and Infectious Disease 8-point ordinal scale and discharge record at Days 7, 14, and 60. The scale is as follows: 1 = Not hospitalized, no limitations on activities; 2=Not hospitalized, limitation on activities and/or requiring home oxygen; 3=Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4=Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 5=Hospitalized, Hospitalized, requiring supplemental oxygen; 6=Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7=Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8=Death.	Days 14, 28, and 60 (Day 60 applies to intubated subjects only)
Secondary	All-cause mortality at Days 7,14, 28, and 60	Number of deaths from any cause	Days 7, 14, 28, and 60 (Day 60 applies to intubated subjects only)
Secondary	Proportion of subjects discharged from hospital at Days 7,14, 28, and 60	Proportion of subjects discharged from hospital at Days 7,14, 28, and 60 (Day 60 applies to intubated subjects only)	Days 7, 14, 28, and 60