The Use of PUL-042 Inhalation Solution to Reduce the Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection

Study Overview
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Brief Summary
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Adults who have tested positive for SARS-CoV-2 infection and who may require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome

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 Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection

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 a positive test for SARS-CoV-2. COVID-19 signs and symptoms such as (fever, cough, shortness of breath or fatigue) with onset within the 7 days prior to Screening Subjects should be Ordinal Scale for Clinical Improvement score of 4 or less. Subjects receiving oxygen should have pulse oximetry ≥ 93% on 3 liters per minute of oxygen or less delivered by nasal prongs. Subjects can be receiving standard of care (SOC) for COVID-19, this includes marketed therapies or therapies with Emergency Use Authorization (EUA) for COVID-19 treatment. Subject's spirometry (FEV1 and forced vital capacity [FVC]) must be ≥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. Must have the ability to understand and give informed consent. Exclusion Criteria: No documented infection with SARS-CoV-2. Patients who are in respiratory distress or require high flow oxygen, non-invasive ventilation or mechanical ventilation (Ordinal Scale for Clinical Improvement >4) or with pulse oximetry less than 93% on oxygen with a flow rate of 3 liters per minute or less by nasal prongs at the time of screening. 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. Exposure to any investigational therapy (defined as any agent not currently marketed or without EUA) at the time of or within 30 days prior to the Screening Visit. Any condition which, in the opinion of the Principal Investigator, would prevent full participation in this trial or would interfere with the evaluation of trial endpoints

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
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 and 6 | Drug: PUL-042 Inhalation Solution<br>* 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042)<br>|
| Placebo Comparator: Sterile saline for inhalation<br>Sterile saline for Inhalation given by nebulization on Study Days 1, 3 and 6 | 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 |
| --- | --- | --- |
| Number of Participants With Worsening of COVID-19 Within 28 Days | To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection, and 2) if receiving oxygen, should have pulse oximetry ≥ 93% on 3 liters per minute of oxygen or less delivered by nasal prongs (Ordinal Scale for Clinical Improvement 4 or less) at the time of enrollment. The primary endpoint analysis is the evaluation of the number of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI used in this study is derived from a draft scale proposed by the World Health Organization for clinical improvement. Higher values represent a worse outcome. The OSCI is a nine-point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive SARS-CoV-2 Test Results at the End of Study | SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy. | 28 days | 
| Number of Participants With Worsening of COVID-19 Over 14 Days | To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is a nine-point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death. | 14 days | 
| Time to COVID-19 Symptom Improvement: Respiratory Symptoms | To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening. The time to respiratory symptom improvement is measured in days. Time to improvement of symptoms was prospectively defined as the time from an initial symptom score of ≥1 to a reduction of ≥1 point. The time to improvement of symptoms was evaluated for each individual symptom listed above. | 28 days | 
| Time to Resolution of COVID-19 Symptoms | The time to resolution of COVID-19 symptoms during the study was measured by the SARS-CoV-2 Symptom Score: The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening. The time to the first occurrence of resolution of symptoms (in days) was defined as the time from the first symptom score of ≥1 to a symptom score of 0. | 28 days | 
| Number of Participants Requiring ICU Admission | The requirement for ICU admission within 28 days from the start of the experimental therapy. | 28 days | 
| Number of Participants Requiring Mechanical Ventilation | The requirement for mechanical ventilation within 28 days from the start of the experimental therapy. | 28 days | 
| Number of Participant Death | All-cause mortality at 28 days from the start of experimental therapy. | 28 days |