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

• ClinicalTrials.gov Identifier: NCT04312997
• Recruitment Status: Completed
• First Posted: March 18, 2020
• Results First Posted: April 18, 2023
• Last Update Posted: April 18, 2023
• Sponsor: Pulmotect, Inc.
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Pulmotect, Inc.

Study Description

Brief Summary:

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

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: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: June 16, 2020
• Actual Primary Completion Date: July 2, 2021
• Actual Study Completion Date: July 2, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Worsening of COVID-19 Within 28 Days [ Time Frame: 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.

Secondary Outcome Measures :

1. Number of Participants With Positive SARS-CoV-2 Test Results at the End of Study [ Time Frame: 28 days ]
   SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy.
2. Number of Participants With Worsening of COVID-19 Over 14 Days [ Time Frame: 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.

3. Time to COVID-19 Symptom Improvement: Respiratory Symptoms [ Time Frame: 28 days ]

   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.

4. Time to Resolution of COVID-19 Symptoms [ Time Frame: 28 days ]

   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.

5. Number of Participants Requiring ICU Admission [ Time Frame: 28 days ]
   The requirement for ICU admission within 28 days from the start of the experimental therapy.
6. Number of Participants Requiring Mechanical Ventilation [ Time Frame: 28 days ]
   The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.
7. Number of Participant Death [ 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 a positive test for SARS-CoV-2.
2. COVID-19 signs and symptoms such as (fever, cough, shortness of breath or fatigue) with onset within the 7 days prior to Screening
3. Subjects should be Ordinal Scale for Clinical Improvement score of 4 or less.
4. Subjects receiving oxygen should have pulse oximetry ≥ 93% on 3 liters per minute of oxygen or less delivered by nasal prongs.
5. 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.
6. Subject's spirometry (FEV1 and forced vital capacity [FVC]) must be ≥70% of predicted value.
7. 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.
8. 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.
9. 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.
10. Must have the ability to understand and give informed consent.

Exclusion Criteria:

1. No documented infection with SARS-CoV-2.
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.
3. 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.
4. 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.
5. 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

Contacts and Locations

Locations

United States, California

University of California Irvine

Orange, California, United States, 92868

Premeir 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

DBC Research Corp.

Tamarac, Florida, United States, 33321

Affinity Clinical Research, LLC

Tampa, Florida, United States, 33612

United States, Kentucky

St. Elizabeth Healthcare

Edgewood, Kentucky, United States, 41017

United States, Oklahoma

Ascension St. John

Bartlesville, Oklahoma, United States, 74006

Ascension St. John

Tulsa, Oklahoma, United States, 74104

United States, Texas

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: NCT04312997
• Other Study ID Numbers: PUL-042-502
• First Posted: March 18, 2020
• Results First Posted: April 18, 2023
• Last Update Posted: April 18, 2023
• Last Verified: March 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