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

• ClinicalTrials.gov Identifier: NCT04313023
• Recruitment Status: Completed
• First Posted: March 18, 2020
• Results First Posted: May 17, 2023
• Last Update Posted: May 17, 2023
• Sponsor: Pulmotect, Inc.
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Pulmotect, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: PUL-042 Inhalation Solution; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: June 9, 2020
• Actual Primary Completion Date: July 31, 2021
• Actual Study Completion Date: July 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: PUL-042 Inhalation Solution; PUL-042 Inhalation Solution given by nebulization on Study Days 1, 3, 6, and 10	Drug: PUL-042 Inhalation Solution; 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042) PUL-042 Inhalation Solution
Placebo Comparator: Sterile saline for inhalation; Sterile saline for inhalation given by nebulization on Study Days 1, 3, 6, and 10	Drug: Placebo; Sterile saline for inhalation

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 28 days ]

   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

Secondary Outcome Measures :

1. Percentage of SARS-CoV-2 Infections Through Day 29 [ Time Frame: 28 days ]
   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.
2. Percentage of SARS-CoV-2 Infections Through Day 15 [ Time Frame: 14 days ]
   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.
3. 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. [ Time Frame: 14 days ]

   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).

4. Number of Participants With ICU Admission [ Time Frame: 28 days ]
   The requirement for ICU admission within 28 days from the start of experimental therapy.
5. Number of Participants Requiring Mechanical Ventilation [ Time Frame: 28 days ]
   The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
6. Number of Participant Deaths [ Time Frame: 28 days ]
   All cause mortality at 28 days from the start of experimental therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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).
2. Subjects must be 50 years or older if the exposure is due to cohabitation.
3. 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.
4. Spirometry (forced expiratory volume in one second FEV1 and forced vital capacity [FVC]) ≥70% of predicted value.
5. 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.
6. 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.
7. 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.
8. Ability to understand and give informed consent.

Exclusion Criteria:

1. Previous infection with SARS-CoV-2.
2. Receipt of any vaccine for the prevention of COVID-19 (single or multiple doses).
3. 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).
4. 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.
5. Any condition which, in the opinion of the Principal Investigator, would prevent full participation

Contacts and Locations

Locations

United States, California

University of California Irvine

Orange, California, United States, 92868

Premier Urgent Care of California

San Bernardino, California, United States, 92404

United States, Florida

Clinical Research of South Florida Alliance for Multispecialty Research

Coral Gables, Florida, United States, 33134

Invesclinic US LLC

Fort Lauderdale, Florida, United States, 33308

Luminous Cinical Research- South Florida Urgent Care

Miami, Florida, United States, 33136

Entrust Clinical Research

Miami, Florida, United States, 33156

DBC Research

Tamarac, Florida, United States, 33321

Affinity Clinical Research, LLC

Tampa, Florida, United States, 33612

United States, Georgia

Clinical Research Atlanta

Stockbridge, Georgia, United States, 30281

United States, Louisiana

Willis-Knighton Physcian Network

Bossier City, Louisiana, United States, 71111

United States, Oklahoma

Ascension St John

Bartlesville, Oklahoma, United States, 74006

Ascension St. John

Tulsa, Oklahoma, United States, 74104

United States, Texas

Invesclinic US LLC

Edinburg, Texas, United States, 78539

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Next Level Urgent Care

Houston, Texas, United States, 77057

Sponsors and Collaborators

Pulmotect, Inc.

United States Department of Defense

Investigators

• Study Director: Colin Broom, MD; Pulmotect, Inc.

  Study Documents (Full-Text)

Documents provided by Pulmotect, Inc.:

Study Protocol and Informed Consent Form  [PDF] January 29, 2021

Statistical Analysis Plan  [PDF] January 29, 2021

More Information

• Responsible Party: Pulmotect, Inc.
• ClinicalTrials.gov Identifier: NCT04313023
• Other Study ID Numbers: PUL-042-501
• First Posted: March 18, 2020
• Results First Posted: May 17, 2023
• Last Update Posted: May 17, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pam2CSK4 acetate and ODN M362 combination; Respiratory System Agents