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

At a glance

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

Most Recent Events

01 Dec 2021 Results published in the Media Release
01 Sep 2021 Status changed from active, no longer recruiting to completed.
14 Jul 2021 Planned number of patients changed from 200 to 217.

Trial Overview

Purpose

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.

Primary Endpoints

Severity of COVID-19

description: 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 within 28 days from the start of experimental therapy.
time_frame: 28 days

Other Endpoints

Percentage of SARS-CoV-2 Infections Through Day 29

description: 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. time_frame: 28 days

Percentage of SARS-CoV-2 Infections Through Day 15

description: 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. time_frame: 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.

description: 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). time_frame: 14 days

Number of Participants With ICU Admission

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

Number of Participant Deaths

description: All cause mortality at 28 days from the start of experimental therapy. time_frame: 28 days^[1]

Diseases Treated

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

Subjects

Subject Type patients
Number
Planned: 217

Actual: 217
Sex male & female
Age Group ≥ 18 years; adult

Patient 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.

Patient 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

Trial Details

Identifiers

Identifier	Owner
NCT04313023	ClinicalTrials.gov: US National Institutes of Health
PUL042-501	-

Organisations

Sponsors Pulmotect
Affiliations Pulmotect

Trial Dates

Initiation Dates
Planned : 01 May 2020

Actual : 09 Jun 2020
Primary Completion Dates
Planned : 30 Jul 2021

Actual : 31 Jul 2021
End Dates
Planned : 30 Jul 2021

Actual : 31 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, 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)

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)

Results

Therapeutic efficacy

Treatment with ODN/Pam2 (PUL 042) inhalation solution, administered as a single dose on days 1, 3, 6, and 10, was effective against all SARS-CoV-2 variants and showed positive efficacy signals, in participants (n=217) with COVID-2019 infections, in a phase II trial. All three PUL 042 treated participants cleared virus by day 15 of the trial, compared with none of the three placebo treated participants. There was no statistically significant difference between treatment groups in the primary endpoint of change in Ordinal Scale for Clinical Improvement (OSCI) although in the prospectively defined subgroup of males were there was a significant difference in favour of PUL 042 (p=0.04)^[2].

Adverse events

Result from the phase II study showed that ODN/Pam2 was well tolerated, and AE differences between groups were not statistically significant. SAEs weren't present.

Treatment with ODN/Pam2 (PUL 042) inhalation solution, administered as a single dose on days 1, 3, 6, and 10, was safe and generally well tolerated, in participants (n=217) with COVID-2019 infections, in a phase II trial. The drug was well tolerated though 28 days of participant follow up, with a low incidence of adverse effects with no drug related serious adverse events reported in the trial and no deaths were reported^[2].

Pharmacodynamics

Result from the phase II trial showed that on both dosing days, ODN/Pam2 significantly and momentarily decreased predicted FEV1 and predicted FVC, but not PEF or FEV1/FVC. By 8 hours, lung function had returned to normal, and the effects of previous dosage days had not accumulated. On both dosing days, ODN/Pam2 resulted in a doubling of blood neutrophils at 4–8 hours after administration (P 0.001), which quickly recovered to baseline within 24 hours. ODN/Pam2 similarly induced a 25% increase at 6h on day -1 (P0.05), however it significantly reduced blood monocytes by 30% at 2h (P0.001, both dosing days). On both dosage days, ODN/Pam2 also displayed non-significant trends for reduced blood lymphocytes. Serum CRP was elevated by ODN/Pam2 by 100% at 8 hours on day 1 (P=0.011) and by 1-300% at 24 hours on day 1 and day 2 (P0.0001 & 0.001, respectively), before returning to baseline. Sputum viral load did not differ significantly between the PUL-042 and placebo groups on day 6, although nasal lavage virus load was lower in the ODN/Pam2 group (P=0.031). Following therapy, ODN/Pam2 demonstrated non-significant trends for transiently elevated levels of sputum and serum IL-6 as well as sputum total cells, neutrophils, lymphocytes, and monocytes. Measurement of the difference in LRS in the treatment group was not possible since there was no RV-induced LRS in the control group.

Publications

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	1	1	1

Trial Centres

Investigators

Download Data (CSV)

Investigator	Centre Name	Trial Centre Country
Aldofo Cueli, MD	Entrust Clinical Research	USA
Alpesh Amin, MD	University of California Irvine	USA
Anuj Malik, MD	Ascension St John, Ascension St. John	USA
Ausberto Hidalgo, MD	Luminous Cinical Research- South Florida Urgent Care	USA
Bernard Garcia, MD	Invesclinic US LLC	USA
Brenton Scott, Ph D 713-579-9226 clincaltrials@pulmotect.com show details		-
Clint Wilson, MD	Willis-Knighton Physcian Network	USA
Colin Broom, MD 832-315-4807 cbroom@pulmotect.com show details	Pulmotect, Inc.	-
David Johnson, MD	Premier Urgent Care of California	USA
German Alvarez, MD	Affinity Clinical Research, LLC	USA
Kevin Bender, MD	DBC Research	USA
Monzer Yazi, MD	Invesclinic US LLC	USA
Nathan Segall, MD	Clinical Research Atlanta	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 Atlanta	Stockbridge, Georgia	USA
Clinical Research of South Florida Alliance for Multispecialty Research	Coral Gables, Florida	USA
DBC Research	Tamarac, Florida	USA
Englewood Health	Englewood, New Jersey	USA
Entrust Clinical Research	Miami, Florida	USA
Invesclinic US LLC	Edinburg, Texas	USA
Invesclinic US LLC	Fort Lauderdale, Florida	USA
Luminous Cinical Research- South Florida Urgent Care	Miami, Florida	USA
MD Anderson Cancer Center	Houston, Texas	USA
Next Level Urgent Care	Houston, Texas	USA
Premier Urgent Care of California	San Bernardino, California	USA
Pulmotect, Inc.	-	-
United States Department of Defense	-	-
University of California Irvine	Orange, California	USA
Willis-Knighton Physcian Network	Bossier City, Louisiana	USA

Trial History

Event Date	Event Type	Comment
19 May 2023	Other trial event	Last checked against Clinicaltrials.gov record. ClinicalTrials.gov: US National Institutes of Health Updated 19 May 2023
01 Dec 2021	Results	Results published in the Media Release Updated 10 Dec 2021
01 Sep 2021	Status change - completed	Status changed from active, no longer recruiting to completed. ClinicalTrials.gov: US National Institutes of Health Updated 06 Sep 2021
14 Jul 2021	Other trial event	Planned number of patients changed from 200 to 217. ClinicalTrials.gov: US National Institutes of Health Updated 19 Jul 2021
14 Jul 2021	Completion date	Planned End Date changed from 1 Jun 2021 to 30 Jul 2021. ClinicalTrials.gov: US National Institutes of Health Updated 19 Jul 2021
14 Jul 2021	Other trial event	Planned primary completion date changed from 1 May 2021 to 30 Jul 2021. ClinicalTrials.gov: US National Institutes of Health Updated 19 Jul 2021
14 Jul 2021	Status change - active, no longer recruiting	Status changed from recruiting to active, no longer recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 19 Jul 2021
22 Feb 2021	Completion date	Planned End Date changed from 1 May 2021 to 1 Jun 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 Apr 2021 to 1 May 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 May 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 Apr 2021. ClinicalTrials.gov: US National Institutes of Health Updated 14 Jan 2021
16 Oct 2020	Completion date	Planned End Date changed from 1 Nov 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 Nov 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
02 Jun 2020	Status change - recruiting	Status changed from not yet recruiting to recruiting. ClinicalTrials.gov: US National Institutes of Health Updated 05 Jun 2020
19 May 2020	Other trial event	According to a Pulmotect media release, he trial is active and will be conducted at up to 10 clinical sites throughout the country, starting with St. Elizabeth in Northern Kentucky, the first hospital site in the world to be able to start dosing patients. Updated 26 May 2020
19 May 2020	Other trial event	According to a Pulmotect media release, St. Elizabeth Healthcare has been selected as the first site of this study in partnership in partnership with CTI - Clinical Trial and Consulting Services (CTI), a global full-service contract research organization. Updated 26 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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