INB03 for the Treatment of Pulmonary Complications From COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.

Detailed Description
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The trial is a Phase 2, double-blind, randomized, placebo-controlled clinical trial of INB03 in participants with pulmonary complications due to COVID-19 infection. Patients with COVID-19 infection and low blood oxygen levels with at least one high risk factor (see below) are eligible to participate in a 40-day study to determine whether INB03 can prevent the progression of pulmonary complications. Eligible participants will be randomized (1:1) to receive either INB03 + standard of care (SOC) or Placebo + SOC. Participants randomized to INB03 + SOC will receive a 1mg/kg injection of INB03 after randomization. Patients that remain in the hospital 7 days after the first dose will receive a second dose. A final safety visit will occur on Day 70.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of INB03 in the Treatment of Participants With Pulmonary Complications From Coronavirus Disease (COVID-19)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: INB03
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have one or more of the following comorbidities: Age ≥ 65 years; Obesity (BMI ≥ 30); Hypertension (on one or more drugs for treatment of hypertension); Diabetes (on one or more drugs for Type I or Type II diabetes); Cardiovascular disease (on one or more drugs for treatment of cardiovascular disease, other than aspirin); History of congestive heart failure (CHF) or myocardial infarction (MI); Black or African-American race (at least one parent identifies as Black or African-American); Hispanic or Latino ethnicity. Have a positive COVID-19 test in the last 28 days; Have room air SaO2 < 96%, or SpO2 < 96% on room air at sea level, or PaO2/FiO2 < 300; Have abnormal chest X-ray, MRI or CT scan consistent with pulmonary complications from COVID-19; Provide written informed consent prior to any study related procedures being performed. Exclusion Criteria: Participants will be excluded from the study if 1 or more of the following criteria are applicable at Screening: Age < 18 years; Require immediate intubation due to advanced respiratory failure - including continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BIPAP); Require immediate admission to an Intensive Care Unit (ICU) for any reason; On therapy with approved TNF inhibitor (eg: infliximab, etanercept, adalimumab, certolizumab pegol, golimumab, thalidomide, etc) in the last 6 months; Being treated with dexamethasone (IV or PO) at a dose of >15mg per day or solumedrol or equivalent corticosteroid at a dose of >75mg per day; Taking any medication known to be CCR5 receptor antagonist (eg: leronlimab, aplaviroc, vicriviroc or maraviroc) in the last 6 months; Taking any medication known to inhibit the cytokine pathway (eg: anakinra, tocilizumab, siltuximab, etc) in the last 6 months; Known to be pregnant; Has known HIV, HCV or HBV infection; Has known Mycobacterium tuberculosis infection or evidence of infection on chest X-ray; Significant hepatic disease (ALT/AST> 4 times the ULN); On therapy for cancer in the last 6 months; On therapy for organ transplant in the last 6 months or on a waiting list for organ transplant, including patients on renal replacement therapy for any reason; Known hypersensitivity to investigational product or its excipients; Participating in an investigational drug or device trial; Congestive heart failure (CHF) or myocardial infarction (MI) diagnosed in the last 2 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo + Standard of Care vs. INB03 + Standard of Care
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Standard of Care<br>Patients will receive placebo + standard medical care | Drug: Placebo<br>* Patients will receive up to two once per week subcutaneous injections of Placebo<br>|
| Experimental: INB03 + Standard of Care<br>Patients will receive INB03 + standard medical care | Drug: INB03<br>* Patients will receive up to two once per week subcutaneous injections of 1mg/kg INB03<br>* Other names: DN-TNF, XPro1595, XENP345, Quellor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with disease progression from randomization to 28 days post-randomization | Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with all-cause mortality |  | 28 days | 
| Proportion of participants who transfer to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is < 4); |  | 28 days | 
| Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28; |  | 28 days | 
| Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28; |  | 28 days | 
| Proportion of participants with a new onset embolus or thrombus by Day 28; |  | 28 days | 
| Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28; |  | 28 days | 
| Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study; |  | 28 days | 
| Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first; |  | 28 days | 
| Change from baseline in inflammation markers over time. |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XPro1595, TNF, DN-TNF, cytokine storm, Quellor, Anti-TNF, Anti-TNF therapy, TNF inhibitor, INB03