The Use PUL-042 to Reduce the Infection Rate and Progression to COVID-19 in Adults Exposed to SARS-CoV-2

Study Overview
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Brief Summary
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Subjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.

Official Title
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A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation Solution in Reducing the Infection Rate and Progression to COVID-19 in Adults Exposed to SARS-CoV-2

Conditions
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COVID-19

Intervention / Treatment
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* Drug: PUL-042 Inhalation Solution
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have recent exposure to SARS-CoV-2 (such as repeated or extensive exposure to an infected individual(s) or cohabiting with a SARS-CoV-2 positive individual). Subjects must be 50 years or older if the exposure is due to cohabitation. Subjects must be free of clinical signs or symptoms of a potential COVID-19 diagnosis (Ordinal Scale of Clinical Improvement score of 0) with a SARS-CoV-2 infection symptom score (fever, cough, shortness of breath, and fatigue) of 0 in each category. Spirometry (forced expiratory volume in one second FEV1 and forced vital capacity [FVC]) ≥70% of predicted value. If female, the subject must be surgically sterile or ≥ 1 year postmenopausal. If of child-bearing potential (including being < 1years postmenopausal) and, if participating in sexual activity that may lead to pregnancy, the subject agrees to use an effective dual method of birth control (acceptable methods include intrauterine device, spermicide, barrier, male partner surgical sterilization, and hormonal contraception) during the study and through 30 days after completion of the study. If female, must not be pregnant, plan to become pregnant, or nurse a child during the study and through 30 days after completion of the study. A pregnancy test must be negative at the Screening Visit, prior to dosing on Day 1. If male, must be surgically sterile or, if not surgically sterile and if participating in sexual activities that may lead to pregnancy, be willing to practice two effective methods of birth control (acceptable methods include barrier, spermicide, or female partner surgical sterilization) during the study and through 30 days after completion of the study. Ability to understand and give informed consent. Exclusion Criteria: Previous infection with SARS-CoV-2. Receipt of any vaccine for the prevention of COVID-19 (single or multiple doses). A SARS-CoV-2 infection symptom score greater than 0 in any of the 4 catergories (fever, cough, shortness of breath or fatigue) at the time of screening (Ordinal Scale for Clinical Improvement score of 0). Known history of chronic pulmonary disease (e.g., asthma [including atopic asthma, exercise-induced asthma, or asthma triggered by respiratory infection], chronic pulmonary disease, pulmonary fibrosis, COPD), pulmonary hypertension, or heart failure. Any condition which, in the opinion of the Principal Investigator, would prevent full participation

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PUL-042 Inhalation Solution<br>PUL-042 Inhalation Solution given by nebulization on Study Days 1, 3, 6, and 10 | Drug: PUL-042 Inhalation Solution<br>* 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042) PUL-042 Inhalation Solution<br>|
| Placebo Comparator: Sterile saline for inhalation<br>Sterile saline for inhalation given by nebulization on Study Days 1, 3, 6, and 10 | Drug: Placebo<br>* Sterile saline for inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of COVID-19: Evaluation of the Severity of COVID-19 as Measured by the Maximum Difference From the Baseline Value in the OSCI Within 28 Days From the Start of Experimental Therapy. | To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement (OSCI) within 28 days from the start of experimental therapy. The OSCI to be used in this study is derived from a draft scale proposed by the World Health Organization for clinical improvement as presented below. The minimum score is 0, maximum is 8. Higher values represent a worse outcome. OSCI Scale: 0 (no evidence of infection), 1 (infected, no limitation of activities), 2 (limitation of activities), 3 (hospitalized), 4 (hospitalized & requiring oxygen), 5 (requiring high flow oxygen), 6 (requiring mechanical ventilation), 7 | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of SARS-CoV-2 Infections Through Day 29 | Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit. | 28 days | 
| Percentage of SARS-CoV-2 Infections Through Day 15 | Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit. | 14 days | 
| Severity of COVID-19: Evaluation of the Severity of COVID-19 as Measured by the Maximum Difference From the Baseline Value in the OSCI Within 14 Days From the Start of Experimental Therapy. | To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement (OSCI) within 14 days from the start of experimental therapy. The Ordinal Scale for Clinical Improvement (OSCI) to be used in this study is derived from a draft scale proposed by the World Health Organization for clinical improvement as presented below. Higher values represent a worse outcome. OSCI Scale: 0 (no evidence of infection), 1 (infected, no limitation of activities), 2 (limitation of activities), 3 (hospitalized), 4 (hospitalized & requiring oxygen), 5 (requiring high flow oxygen), 6 (requiring mechanical ventilation), 7 (requiring RRT, ECMO etc.), 8 (death). | 14 days | 
| Number of Participants With ICU Admission | The requirement for ICU admission within 28 days from the start of experimental therapy. | 28 days | 
| Number of Participants Requiring Mechanical Ventilation | The requirement for mechanical ventilation within 28 days from the start of experimental therapy. | 28 days | 
| Number of Participant Deaths | All cause mortality at 28 days from the start of experimental therapy. | 28 days |