Treatment and Prevention of Acute Lung Injury (ALI) in Patients With COVID-19 Infection

Study Overview
=================
Brief Summary
-----------------
The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

Detailed Description
-----------------
This is a randomized, double-blind, placebo-controlled study intended to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Efficacy will be assessed during the 28 days following a single administration of VIB7734. Safety will be assessed for 10 weeks following dosing. The pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of VIB7734 in patients with confirmed SARS-CoV-2 infections will also be assessed.

Official Title
-----------------
A Proof of Concept Study of the Safety and Efficacy of VIB7734 for the Treatment and Prevention of Acute Lung Injury (ALI) in Patients With SARS-CoV-2 Infection

Conditions
-----------------
Acute Lung Injury

Intervention / Treatment
-----------------
* Drug: VIB7734
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Hospitalized with coronavirus disease 2019 (COVID-19) pneumonia confirmed by World Health Organization criteria. Oxygen saturation ≤ 94% at room air or arterial partial pressure of oxygen/fraction of inspired oxygen < 300 mm Hg and > 200 mm Hg. Negative influenza test. Lymphocyte counts < 10^3/μL and the presence of at least one of the following markers of hyperinflammation within 1 day prior to VIB7734 administration: Elevated high sensitivity C-reactive protein (hsCRP) > 50 mg/L Ferritin > 500 ng/mL Lactate dehydrogenase (LDH) > 300 U/L D-dimers > 500 ng/mL NOTE: Other protocol defined inclusion criteria apply Key Exclusion Criteria: Respiratory failure requiring mechanical ventilation. In the opinion of the Investigator, progression to mechanical ventilation or death is imminent and inevitable within the next 24 hours. Valid Do Not Intubate (DNI) or Do Not Resuscitate (DNR) order. Anticipated duration of hospital stay < 72 hours. History of allergy or hypersensitivity reaction to any component of the IP. Participation in another clinical study with an IP within 4 weeks prior to Day 1 or within 5 half-lives of the IP, whichever is longer. (Participation in COVID-19 antiviral or antimalarial trials may be permitted after discussion with the Medical Monitor). Liver cirrhosis or liver failure. Known human immunodeficiency virus infection. Known hepatitis B or known hepatitis C infection in the absence of a history of curative therapy. Known or suspect active or latent tuberculosis infection. Active bacterial, fungal, viral, or other infection (besides COVID-19). Clinically significant cardiac disease within 6 months. History of severely impaired respiratory function at baseline (not related to COVID-19) based on requirement for home oxygen of > 4 L/min or based on other medical history known to the Investigator. History of cancer within 12 months of enrollment. Receipt of chemotherapy, biologic immunomodulators (including JAK inhibitors), or immunosuppressive therapies within 8 weeks of enrollment, or receipt of rituximab or other B cell-depleting mAb therapy within 6 months. NOTE: Other protocol defined exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIB7734 Dose<br>Participants will receive a single subcutaneous dose of VIB7734. | Drug: VIB7734<br>* Single subcutaneous dose<br>|
| Placebo Comparator: Placebo<br>Participants will receive a single subcutaneous dose of placebo (saline) matched to single dose of VIB7734. | Drug: Placebo<br>* Intravenous single dose matched to VIB7734.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients who achieve treatment success through Day 28, defined as avoidance of death and critical illness | Critical illness is defined by respiratory failure (requiring any of the following: endotracheal intubation, oxygen delivered by high flow nasal cannula, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation or clinical diagnosis of respiratory failure) or shock (systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg, or requiring vasopressors) | Day 1 (Baseline) through Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent fatal and life-threatening SAEs, Treatment-emergent Serious Adverse Events | Defined as measure of safety | Day 1 (Baseline) through Day 70 | 
| Change in safety laboratory parameters | Safety evaluation via review of labs (white blood cell (WBC) with differential counts, hemoglobin, platelet count, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin levels), serum chemistry, cardiac troponin coagulation markers (prothrombin time [PT], partial thromboplastin time [PTT], D dimer, fibrinogen), and urinalysis) | Day 1 (Baseline) through Day 70 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pneumonia, COVID-19, SARS-Cov-2, acute respiratory disease