COVID-19
Conditions
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.
Interventions
20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042) PUL-042 Inhalation Solution
DRUGPlacebo
Sterile saline for inhalation
Sponsors
United States Department of Defense
Pulmotect, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of SARS-CoV-2 Infections Through Day 15 | 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. |
| 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. | 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). |
| Percentage of SARS-CoV-2 Infections Through Day 29 | 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. |
| Number of Participants Requiring Mechanical Ventilation | 28 days | The requirement for mechanical ventilation within 28 days from the start of experimental therapy. |
| Number of Participant Deaths | 28 days | All cause mortality at 28 days from the start of experimental therapy. |
| Number of Participants With ICU Admission | 28 days | The requirement for ICU admission within 28 days from the start of experimental therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PUL-042 Inhalation Solution PUL-042 Inhalation Solution given by nebulization on Study Days 1, 3, 6, and 10
PUL-042 Inhalation Solution: 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042) PUL-042 Inhalation Solution | 102 |
| Sterile Saline for Inhalation Sterile saline for inhalation given by nebulization on Study Days 1, 3, 6, and 10
Placebo: Sterile saline for inhalation | 108 |
| Total | 210 |
Baseline characteristics
| Characteristic | Total | PUL-042 Inhalation Solution | Sterile Saline for Inhalation |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 11 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 190 Participants | 91 Participants | 99 Participants |
| Age, Continuous | 47.1 years STANDARD_DEVIATION 14.09 | 48.6 years STANDARD_DEVIATION 13.64 | 45.6 years STANDARD_DEVIATION 14.4 |
| BMI | 29.15 kg/m^2 STANDARD_DEVIATION 5.347 | 29.29 kg/m^2 STANDARD_DEVIATION 5.619 | 29.02 kg/m^2 STANDARD_DEVIATION 5.099 |
| Duration of Exposure | 31.6 days STANDARD_DEVIATION 51.54 | 29.7 days STANDARD_DEVIATION 44.28 | 33.4 days STANDARD_DEVIATION 57.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 146 Participants | 68 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 34 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| percentage of predicted FEV1 | 94.93 Percent STANDARD_DEVIATION 17.832 | 94.86 Percent STANDARD_DEVIATION 18.277 | 94.99 Percent STANDARD_DEVIATION 17.487 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 16 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 175 Participants | 83 Participants | 92 Participants |
| Region of Enrollment United States | 210 participants | 102 participants | 108 participants |
| Sex: Female, Male Female | 120 Participants | 60 Participants | 60 Participants |
| Sex: Female, Male Male | 90 Participants | 42 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 108 |
| other Total, other adverse events | 28 / 102 | 10 / 108 |
| serious Total, serious adverse events | 0 / 102 | 0 / 108 |
Outcome results
Primary
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.
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
Time frame: 28 days
Population: The population analyzed is the ITT (Intent-to-Treat) population minus one participant on PUL-042 that was excluded due to an absent baseline measurement.~ITT total: 210; ITT placebo: 108; ITT PUL-042: 102
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PUL-042 Inhalation Solution | 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. | 0.028 score on a scale |
| Sterile Saline for Inhalation | 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. | 0.048 score on a scale |
Secondary
Number of Participant Deaths
All cause mortality at 28 days from the start of experimental therapy.
Time frame: 28 days
Population: A total of 217 participants were randomized to the study: 7 participants were randomized but not treated, 210 (96.8%) participants were included in the ITT (Intent-to-Treat) Population and Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PUL-042 Inhalation Solution | Number of Participant Deaths | 0 Participants |
| Sterile Saline for Inhalation | Number of Participant Deaths | 0 Participants |
Secondary
Number of Participants Requiring Mechanical Ventilation
The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
Time frame: 28 days
Population: A total of 217 participants were randomized to the study: 7 participants were randomized but not treated, 210 (96.8%) participants were included in the ITT (Intent-to-Treat) Population and Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PUL-042 Inhalation Solution | Number of Participants Requiring Mechanical Ventilation | 0 Participants |
| Sterile Saline for Inhalation | Number of Participants Requiring Mechanical Ventilation | 0 Participants |
Secondary
Number of Participants With ICU Admission
The requirement for ICU admission within 28 days from the start of experimental therapy.
Time frame: 28 days
Population: A total of 217 participants were randomized to the study: 7 participants were randomized but not treated, 210 (96.8%) participants were included in the ITT (Intent-to-Treat) Population and Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PUL-042 Inhalation Solution | Number of Participants With ICU Admission | 0 Participants |
| Sterile Saline for Inhalation | Number of Participants With ICU Admission | 0 Participants |
Secondary
Percentage of SARS-CoV-2 Infections Through Day 15
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
Population: Percentage of participants who had a positive result from the SARS-CoV-2 test within 14 days from the first dose of study drug was assessed using the modified ITT Set.~Participants who had a missing test result or a result of Indeterminate at Day 29 and did not have a positive test result at Day 15 were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PUL-042 Inhalation Solution | Percentage of SARS-CoV-2 Infections Through Day 15 | 2.17 percentage of participants |
| Sterile Saline for Inhalation | Percentage of SARS-CoV-2 Infections Through Day 15 | 2.13 percentage of participants |
Secondary
Percentage of SARS-CoV-2 Infections Through Day 29
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
Population: Percentage of participants who had a positive result from the SARS-CoV-2 test within 28 days from the first dose of study drug was assessed using the modified ITT Set.~Participants who had a missing test result or a result of Indeterminate at Day 29 and did not have a positive test result at Day 15 were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PUL-042 Inhalation Solution | Percentage of SARS-CoV-2 Infections Through Day 29 | 3.37 percentage of participants |
| Sterile Saline for Inhalation | Percentage of SARS-CoV-2 Infections Through Day 29 | 3.23 percentage of participants |
Secondary
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.
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
Population: The population analyzed is the ITT (Intent-to-Treat) population minus one participant on PUL-042 that was excluded due to an absent baseline measurement.~ITT total: 210; ITT placebo: 108; ITT PUL-042: 102
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PUL-042 Inhalation Solution | 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. | 0.018 score on a scale |
| Sterile Saline for Inhalation | 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. | 0.048 score on a scale |