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

At a glance

Drugs ODN/Pam2 (Primary)
Indications COVID 2019 infections; SARS-CoV-2 acute respiratory disease
Focus Therapeutic Use
Sponsors Pulmotect

Most Recent Events

01 Dec 2021 Results published in the Media Release
24 Sep 2021 Primary endpoint has been met. (Severity of COVID-19) as per Pulmotect media release
24 Sep 2021 Results published in the Pulmotect Media Release

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

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

Primary Endpoints

Met on 24 Oct 2021

Severity of COVID-19

description: 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 is the difference in the proportion 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.
The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
time_frame: 28 days^[1]

Other Endpoints

Number of Participants With Positive SARS-CoV-2 Test Results at the End of Study

description: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy. time_frame: 28 days

Number of Participants With Worsening of COVID-19 Over 14 Days

description: 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. time_frame: 14 days

Time to COVID-19 Symptom Improvement: Respiratory Symptoms

description: 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. time_frame: 28 days

Time to Resolution of COVID-19 Symptoms

description: 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. time_frame: 28 days

Number of Participants Requiring ICU Admission

description: The requirement for ICU admission within 28 days from the start of the experimental therapy. time_frame: 28 days

Number of Participants Requiring Mechanical Ventilation

description: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy. time_frame: 28 days

Number of Participant Death

description: All-cause mortality at 28 days from the start of experimental therapy. time_frame: 28 days^[2]

Diseases Treated

Indication	Qualifiers	Patient Segments
COVID 2019 infections	treatment	-
SARS-CoV-2 acute respiratory disease	treatment	-

Subjects

Subject Type patients
Number
Planned: 100

Actual: 101
Sex male & female
Age Group ≥ 18 years; adult

Patient 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.

Patient 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

Trial Details

Identifiers

Identifier	Owner
NCT04312997	ClinicalTrials.gov: US National Institutes of Health
PUL042-502	-

Organisations

Sponsors Pulmotect
Affiliations Pulmotect

Trial Dates

Initiation Dates
Planned : 01 May 2020

Actual : 16 Jun 2020
Primary Completion Dates
Planned : 02 Jul 2021

Actual : 02 Jul 2021
End Dates
Planned : 01 Aug 2021

Actual : 02 Jul 2021

Other Details

Design double-blind; multicentre; parallel; prospective; randomised
Phase of Trial Phase II
Location USA
Focus Therapeutic Use

Drug Name	Highest Phase	Originator
ODN/Pam2 - Pulmotect	Phase II	Pulmotect

Interventions

Drugs	Route	Formulation
ODN/Pam2Primary Drug	Inhalation	Solution

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))

Sterile saline for inhalation

Sterile saline for Inhalation given by nebulization on Study Days 1, 3 and 6
Drug: Placebo (Sterile saline for inhalation)

Results

Therapeutic efficacy

Updated results of the double-blind, randomised, phase II trial in adults positive for SARS-CoV-2 infection demonstrated that statistically significant reduction in the time to improvement of the combined respiratory symptoms of cough and shortness of breath with ODN/Pam2 (PUL 042) inhalation treatment, delivered by PARI's LC Sprint reusable nebulizer. PUL 042 inhalation solution reduced the severity of COVID-2019 infection (n = 101), in a prospectively defined endpoints and analyses included evaluation of the cardinal symptoms of COVID-2019 infection, including cough, shortness of breath, respiratory symptoms (cough and shortness of breath) and fatigue. Each individual symptom was scored as 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). There was a statistically significant difference in time to improvement of respiratory symptoms (p=0.0227) using a log-rank comparison of time to symptom improvement. The median time to improvement of respiratory symptoms was six days for PUL 042 and nine days for placebo. The time to complete resolution of respiratory symptoms also trended in favor of PUL 042. There was also a positive effect on time to improvement of cough (p=0.0547). The median time to improvement of cough was seven days for PUL 042 and 11 days for placebo^[3]^[1].

Adverse events

In a phase II trial of PUL 042 inhalation solution in reducing the severity of COVID-19 infection with positive SARS-CoV-2 infection (n=101), PUL 042 was well tolerated when administered as a single dose on Day 1, Day 3 and Day 6 of the trial with 28 days of patient follow up. The drug was well tolerated with a low incidence of adverse effects with no drug related serious adverse events reported in the trial. Two patients were hospitalised with a deterioration from pre-treatment of 2 or more points on the Ordinal Scale for Clinical Improvement, a nine-point scale proposed by the World Health Organization, one in each of the treatment arms. In total, three patients were hospitalised for progression of COVID-19, two in the placebo arm who both required intensive care treatment for 5 days and 9 days and one patient in the PUL 042 arm who was hospitalised for four days having received a single dose of PUL 042 and did not require intensive care^[1].

Publications

Pulmotect. Pulmotect Reports Positive Topline Results from Randomized, Placebo Controlled Phase-2 Trial of PUL-042 against COVID-19. Media-Rel 2021;.
Media Release
Pulmotect. Pulmotect's Positive Topline Results for Inhaled PUL-042 against COVID-19 Delivered by PARI Nebulizer. Media-Rel 2021;.
Media Release
Pulmotect. Pulmotect Provides Results from Two Randomized, Placebo Controlled Phase-2 Trials of PUL-042 Against COVID-19. Media-Rel 2021;.
Media Release

Authors

Author	Total Publications	First Author	Last Author
Pulmotect	3	3	3

Trial Centres

Investigators

Download Data (CSV)

Investigator	Centre Name	Trial Centre Country
Alpesh Amin, MD	University of California Irvine	USA
Anuj Malik, MD	Ascension St. John	USA
Bernard Garcia, MD	Invesclinic US LLC	USA
Brenton Scott, Ph D 713-579-9226 clinicaltrials@pulmotect.com show details		-
Chai Mandapakala, MD	St. Elizabeth Healthcare	USA
Colin Broom, MD 832-315-4807 cbroom@pulmotect.com show details	Pulmotect, Inc.	-
David Johnson, MD	Premeir Urgent Care of California	USA
German Alvarez, MD	Affinity Clinical Research, LLC	USA
Jeffrey B Rosen, MD	Clinical Research of South Florida Alliance for Multispecialty Research	USA
Kevin Bender, MD	DBC Research Corp.	USA
Tapan Kadia, MD	MD Anderson Cancer Center	USA
Terrance M Chang, MD	Next Level Urgent Care	USA

Centres

Download Data (CSV)

Centre Name	Location	Trial Centre Country
-	-	-
Affinity Clinical Research, LLC	Tampa, Florida	USA
Ascension St. John	Bartlesville, Oklahoma	USA
Ascension St. John	Tulsa, Oklahoma	USA
Clinical Research of South Florida Alliance for Multispecialty Research	Coral Gables, Florida	USA
DBC Research Corp.	Tamarac, Florida	USA
Invesclinic US LLC	Fort Lauderdale, Florida	USA
MD Anderson Cancer Center	Houston, Texas	USA
Next Level Urgent Care	Houston, Texas	USA
Premeir Urgent Care of California	San Bernardino, California	USA
Pulmotect, Inc.	-	-
St. Elizabeth Healthcare	Edgewood, Kentucky	USA
United States Department of Defense	-	-
University of California Irvine	Orange, California	USA

Trial History

Event Date	Event Type	Comment
20 Apr 2023	Other trial event	Last checked against Clinicaltrials.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 20 Apr 2023
01 Dec 2021	Results	Results published in the Media Release Updated 10 Dec 2021
29 Sep 2021	Results	Topline results presented in a Pulmotect media release. Updated 05 Jan 2022
24 Sep 2021	Endpoint met	Primary endpoint has been met. (Severity of COVID-19) as per Pulmotect media release Updated 05 Oct 2021
24 Sep 2021	Results	Results published in the Pulmotect Media Release Updated 05 Oct 2021
14 Jul 2021	Status change - completed	Status changed from active, no longer recruiting to completed. ClinicalTrials.gov: US National Institutes of Health Updated 19 Jul 2021
15 Jun 2021	Completion date	Planned End Date changed from 1 Jul 2021 to 1 Aug 2021. ClinicalTrials.gov: US National Institutes of Health Updated 21 Jun 2021
15 Jun 2021	Other trial event	Planned primary completion date changed from 1 Jun 2021 to 2 Jul 2021. ClinicalTrials.gov: US National Institutes of Health Updated 21 Jun 2021
15 Jun 2021	Status change - active, no longer recruiting	Status changed from recruiting to active, no longer recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 21 Jun 2021
28 May 2021	Completion date	Planned End Date changed from 1 May 2021 to 1 Jul 2021. ClinicalTrials.gov: US National Institutes of Health Updated 07 Jun 2021
28 May 2021	Other trial event	Planned primary completion date changed from 1 Apr 2021 to 1 Jun 2021. ClinicalTrials.gov: US National Institutes of Health Updated 07 Jun 2021
22 Feb 2021	Completion date	Planned End Date changed from 1 Apr 2021 to 1 May 2021. ClinicalTrials.gov: US National Institutes of Health Updated 25 Feb 2021
22 Feb 2021	Other trial event	Planned primary completion date changed from 1 Mar 2021 to 1 Apr 2021. ClinicalTrials.gov: US National Institutes of Health Updated 25 Feb 2021
12 Jan 2021	Completion date	Planned End Date changed from 1 Mar 2021 to 1 Apr 2021. ClinicalTrials.gov: US National Institutes of Health Updated 14 Jan 2021
12 Jan 2021	Other trial event	Planned primary completion date changed from 1 Jan 2021 to 1 Mar 2021. ClinicalTrials.gov: US National Institutes of Health Updated 14 Jan 2021
16 Oct 2020	Completion date	Planned End Date changed from 1 Dec 2020 to 1 Mar 2021. ClinicalTrials.gov: US National Institutes of Health Updated 22 Oct 2020
16 Oct 2020	Other trial event	Planned primary completion date changed from 1 Oct 2020 to 1 Jan 2021. ClinicalTrials.gov: US National Institutes of Health Updated 22 Oct 2020
03 Sep 2020	Completion date	Planned End Date changed from 1 Oct 2020 to 1 Dec 2020. ClinicalTrials.gov: US National Institutes of Health Updated 07 Sep 2020
03 Sep 2020	Other trial event	Planned primary completion date changed from 1 Sep 2020 to 1 Oct 2020. ClinicalTrials.gov: US National Institutes of Health Updated 07 Sep 2020
11 May 2020	Status change - recruiting	Status changed from not yet recruiting to recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 13 May 2020
07 May 2020	Other trial event	According to a Pulmotect media release , the company informed that in this week the first patient is enrolling in this study. Updated 11 May 2020
05 May 2020	Other trial event	According to a Pulmotect media release, the company has received approval from the U.S. Food & Drug Administration (FDA) to initiate this study. Updated 26 May 2020
04 May 2020	Other trial event	Planned initiation date changed from 1 Apr 2020 to 1 May 2020. ClinicalTrials.gov: US National Institutes of Health Updated 07 May 2020
23 Mar 2020	New trial record	New trial record ClinicalTrials.gov: US National Institutes of Health Updated 23 Mar 2020

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