Coronavirus Infection, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), COVID-19 Disease
Conditions
Keywords
DNA vaccine, Electroporation, Healthy, COVID-19
Brief summary
This is a Phase 2/3, randomized, placebo-controlled, multi-center trial to evaluate the safety, immunogenicity and efficacy of INO-4800 administered by intradermal (ID) injection followed by electroporation (EP) using CELLECTRA® 2000 device to prevent coronavirus disease 2019 (COVID-19) in participants at high risk of exposure to severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2). The Phase 2 segment will evaluate immunogenicity and safety in approximately 400 participants at two dose levels across three age groups. Safety and immunogenicity information from the Phase 2 segment will be used to determine the dose level for the Phase 3 efficacy segment of the study involving approximately 7116 participants.
Interventions
DRUGINO-4800
INO-4800 was administered ID on Day 0 and Day 28.
DEVICECELLECTRA® 2000
EP using the CELLECTRA® 2000 device was administered following ID delivery of INO-4800 on Day 0 and Day 28.
DRUGPlacebo
Sterile saline sodium citrate (SSC) buffer (SSC-0001) was administered ID on Day 0 and Day 28.
Sponsors
Advaccine (Suzhou) Biopharmaceuticals Co., Ltd.
Inovio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Working or residing in an environment with high risk of exposure to SARS-CoV-2 for whom exposure may be relatively prolonged or for whom personal protective equipment (PPE) may be inconsistently used, especially in confined settings. * Phase 2 only: Screening laboratory results within normal limits for testing laboratory or are deemed not clinically significant by the Investigator. * Be post-menopausal or be surgically sterile or have a partner who is sterile or use medically effective contraception with a failure rate of \< 1% per year when used consistently and correctly from Screening until 3 months following last dose (Phase 2) or until last dose (Phase 3). Key
Exclusion criteria
* Acute febrile illness with temperature higher than or equal to 100.4°F (38.0°C) or acute onset of upper or lower respiratory tract symptoms (e.g., cough, shortness of breath, sore throat). * Positive serologic or molecular (Reverse transcription polymerase chain reaction (RT-PCR)) test for SARS-CoV-2 at Screening (this criterion applies to all Phase 2 participants and only applies after approximately 402 participants positive for SARS-CoV-2 serologic test are randomized in the Phase 3 segment of the study). * Pregnant or breastfeeding or intending to become pregnant or intending to father children within the projected duration of the trial starting from the Screening visit until 3 months following the last dose (Phase 2) or until last dose (Phase 3). * Known history of uncontrolled human immunodeficiency virus (HIV) based on clusters of differentiation (CD4) count less than 200 cells per cubic millimeter (/mm\^3) or a detectable viral load within the past 3 months. * Is currently participating or has participated in a study with an investigational product within 30 days preceding Day 0. * Previous or planned receipt of an investigational (including Emergency Use Authorization (EUA) or local equivalent authorization) or licensed vaccine for prevention or treatment of COVID-19, middle east respiratory syndrome (MERS), or severe acute respiratory syndrome (SARS) (documented receipt of placebo in previous trial would be permissible for trial eligibility). * Respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease) requiring significant changes in therapy or hospitalization for worsening disease during the 6 weeks prior to enrolment. * Immunosuppression as a result of underlying illness or treatment. * Lack of acceptable sites available for ID injection and EP. * Blood donation or transfusion within 1 month prior to Day 0. * Reported alcohol or substance abuse or dependence, or illicit drug use (excluding marijuana use). * Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Baseline up to Week 6 | Whole blood and serum samples were collected for the cellular immunology assessment. The antigen-specific cellular immune response to INO-4800 was measured in spot-forming units per million peripheral blood mononuclear cells (SFU/10\^6, PBMC) using ELISpot. No samples collected after Week 6 were analyzed. |
| Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline up to Week 6 | The immune responses to INO-4800 were measured using assays that included a pseudovirus-based neutralization assay. Immunology blood samples were collected at serial timepoints. No samples collected after Week 6 were analyzed. |
| Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Virologically-confirmed COVID-19 Disease | From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126) | Participants were virologically-confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. Participants with no prior exposure to COVID-19 at baseline were considered for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35) | An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants were provided a diary to record the solicited systemic AEs. The solicited AEs were recorded for 7 days after each dose. |
| Phase 2 and 3: Percentage of Participants With Unsolicited AEs | From first dose of study drug up to Day 56 | An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AEs were recorded for up to 28 days after administration of dose 2. |
| Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126 | An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly or birth defect. |
| Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126 | An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. |
| Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Non-Severe COVID-19 Disease | From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126) | The efficacy of INO-4800 in the prevention of COVID-19 disease was evaluated according to the degrees of COVID-19 disease severity in participants. Participants were confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. The case definition of severe COVID-19 was participants with COVID-19 having clinical signs at rest indicative of severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to an intensive care unit, or death. The case definition for non-severe COVID-19 was participants with confirmed COVID-19, and which did not meet the case definition of severe COVID-19. |
| Phase 3: Number of Participants With Death From All Causes | Baseline up to Day 126 | — |
| Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Death From COVID-19 Disease | From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126) | — |
| Phase 3: Percentage of Participants (SARS-CoV-2 Seropositive at Baseline) With Virologically-Confirmed SARS-CoV-2 COVID-19 Disease | From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126) | Participants were virologically-confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. Participants with prior exposure to COVID-19 at baseline were considered for the analysis. |
| Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay | Baseline up to Day 126 | Whole blood and serum samples were collected for the cellular immunology assessment. The antigen-specific cellular immune response to INO-4800 were measured using ELISpot. |
| Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline up to Day 126 | The immune responses to INO-4800 were measured using assays that included a pseudovirus-based neutralization assay. |
| Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Severe COVID-19 Disease | From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126) | The efficacy of INO-4800 in the prevention of COVID-19 disease was evaluated according to the degrees of COVID-19 disease severity in participants. Participants were confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. The case definition of severe COVID-19 was participants with COVID-19 having clinical signs at rest indicative of severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to an intensive care unit, or death. |
| Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35) | Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration \[FDA\] Guidance for Industry, September 2007). Participants were provided a diary to record the solicited injection site reactions. Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were recorded. Injection site reactions were evaluated starting 30 minutes following the injection. The solicited injection site reactions were recorded for 7 days after each dose. |
| Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | From first dose of study drug up to Day 56 | Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' FDA Guidance for Industry, September 2007. Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were reported. Injection site reactions were evaluated starting 30 minutes following the injection. Unsolicited injection site reactions were recorded for up to 28 days after administration of dose 2. |
Countries
Colombia, Mexico, United States
Participant flow
Recruitment details
For the phase 2 segment, participants were enrolled at 16 study sites in the United States. For the Phase 3 segment, participants were enrolled at 11 study sites in Colombia and Mexico. They were enrolled between 30 November 2020 to 13 September 2022
Pre-assignment details
In the Phase 2 segment, 618 participants were screened, of which 401 participants were enrolled to receive INO-4800 or placebo. In the Phase 3 segment, 978 participants were screened, of which 906 participants were enrolled to receive INO-4800 or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Phase 2: INO-4800 Dose Group 1 Participants received one ID injection of 1.0 mg of INO-4800 followed by electroporation (EP) using the CELLECTRA® 2000 device on Day 0 and Day 28. | 151 |
| Phase 2: INO-4800 Dose Group 2 Participants received 2 ID injections of 1.0 mg (total 2.0 mg per dosing visit) of INO-4800 followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28. | 149 |
| Phase 2: Placebo Dose Group 1 Participants received one ID injection of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28. | 50 |
| Phase 2: Placebo Dose Group 2 Participants received 2 ID injections of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28. | 51 |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) Participants received two 1.0 mg ID injections of INO-4800, each followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28. | 603 |
| Phase 3: Placebo Dose Group Participants received 2 ID injections of placebo per dosing visit, each followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28. | 303 |
| Total | 1,307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 10 | 3 |
| Overall Study | Lost to Follow-up | 17 | 18 | 5 | 5 | 6 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 2 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Deviation | 0 | 0 | 0 | 0 | 1 | 3 |
| Overall Study | Reason Not Specified | 1 | 4 | 0 | 0 | 38 | 16 |
| Overall Study | Study Terminated | 0 | 0 | 0 | 0 | 484 | 250 |
| Overall Study | Withdrawal by Subject | 23 | 29 | 9 | 7 | 61 | 27 |
Baseline characteristics
| Characteristic | Phase 2: INO-4800 Dose Group 1 | Phase 2: INO-4800 Dose Group 2 | Phase 2: Placebo Dose Group 1 | Phase 2: Placebo Dose Group 2 | Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 3: Placebo Dose Group | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized Age 18-50 years | 98 Participants | 97 Participants | 32 Participants | 34 Participants | 533 Participants | 267 Participants | 1061 Participants |
| Age, Customized Age 51-64 years | 41 Participants | 40 Participants | 14 Participants | 13 Participants | 63 Participants | 29 Participants | 200 Participants |
| Age, Customized Age >=65 years | 12 Participants | 12 Participants | 4 Participants | 4 Participants | 7 Participants | 7 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 14 Participants | 7 Participants | 9 Participants | 601 Participants | 300 Participants | 960 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 122 Participants | 134 Participants | 43 Participants | 42 Participants | 1 Participants | 3 Participants | 345 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants | 2 Participants | 314 Participants | 171 Participants | 491 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 8 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 16 Participants | 5 Participants | 2 Participants | 2 Participants | 2 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 267 Participants | 123 Participants | 394 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 127 Participants | 121 Participants | 45 Participants | 44 Participants | 20 Participants | 7 Participants | 364 Participants |
| Sex: Female, Male Female | 76 Participants | 77 Participants | 28 Participants | 30 Participants | 245 Participants | 120 Participants | 576 Participants |
| Sex: Female, Male Male | 75 Participants | 72 Participants | 22 Participants | 21 Participants | 358 Participants | 183 Participants | 731 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 151 | 0 / 147 | 1 / 50 | 0 / 51 | 2 / 601 | 2 / 302 |
| other Total, other adverse events | 115 / 151 | 127 / 147 | 42 / 50 | 38 / 51 | 279 / 601 | 140 / 302 |
| serious Total, serious adverse events | 4 / 151 | 2 / 147 | 3 / 50 | 2 / 51 | 4 / 601 | 4 / 302 |
Outcome results
Primary
Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay
Whole blood and serum samples were collected for the cellular immunology assessment. The antigen-specific cellular immune response to INO-4800 was measured in spot-forming units per million peripheral blood mononuclear cells (SFU/10\^6, PBMC) using ELISpot. No samples collected after Week 6 were analyzed.
Time frame: Baseline up to Week 6
Population: PP population included all participants who received all doses of the trial intervention and had no key protocol violations. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' denotes the number of participants available at individual timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Baseline | 0.00 SFU/10^6, PBMC |
| Phase 2: INO-4800 Dose Group 1 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Change From Baseline at Week 6 | 6.70 SFU/10^6, PBMC |
| Phase 2: INO-4800 Dose Group 2 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Change From Baseline at Week 6 | 13.30 SFU/10^6, PBMC |
| Phase 2: INO-4800 Dose Group 2 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Baseline | 2.20 SFU/10^6, PBMC |
| Phase 2: Placebo Dose Group 1 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Baseline | 0.00 SFU/10^6, PBMC |
| Phase 2: Placebo Dose Group 1 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Change From Baseline at Week 6 | 0.00 SFU/10^6, PBMC |
| Phase 2: Placebo Dose Group 2 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Baseline | 0.00 SFU/10^6, PBMC |
| Phase 2: Placebo Dose Group 2 | Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay | Change From Baseline at Week 6 | 0.00 SFU/10^6, PBMC |
95% CI: [-10, 0]
95% CI: [0, 6.7]
95% CI: [3.3, 17.8]
Primary
Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay
The immune responses to INO-4800 were measured using assays that included a pseudovirus-based neutralization assay. Immunology blood samples were collected at serial timepoints. No samples collected after Week 6 were analyzed.
Time frame: Baseline up to Week 6
Population: PP population included all participants who received all doses of the trial intervention and had no key protocol violations. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' denotes the number of participants available at individual timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline | 34.8 inhibition dilution 50 (ID50) | Standard Deviation 0.42 |
| Phase 2: INO-4800 Dose Group 1 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Change From Baseline at Week 6 | 3.1 inhibition dilution 50 (ID50) | Standard Deviation 0.49 |
| Phase 2: INO-4800 Dose Group 2 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Change From Baseline at Week 6 | 4.6 inhibition dilution 50 (ID50) | Standard Deviation 0.52 |
| Phase 2: INO-4800 Dose Group 2 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline | 40.6 inhibition dilution 50 (ID50) | Standard Deviation 0.52 |
| Phase 2: Placebo Dose Group 1 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline | 30.2 inhibition dilution 50 (ID50) | Standard Deviation 0.4 |
| Phase 2: Placebo Dose Group 1 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Change From Baseline at Week 6 | 1.2 inhibition dilution 50 (ID50) | Standard Deviation 0.39 |
| Phase 2: Placebo Dose Group 2 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Baseline | 38.0 inhibition dilution 50 (ID50) | Standard Deviation 0.45 |
| Phase 2: Placebo Dose Group 2 | Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay | Change From Baseline at Week 6 | 1.2 inhibition dilution 50 (ID50) | Standard Deviation 0.49 |
95% CI: [1.72, 3.632]
95% CI: [2.638, 5.7]
95% CI: [0.512, 0.893]
Primary
Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Virologically-confirmed COVID-19 Disease
Participants were virologically-confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. Participants with no prior exposure to COVID-19 at baseline were considered for the analysis.
Time frame: From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126)
Population: For the Phase 3 segment, as pre-specified in the protocol, an independent endpoint adjudication committee (EAC) was to review and confirm the suspected COVID-19 cases which fulfilled the definition for virologically-confirmed COVID-19 cases. As the trial was prematurely terminated, suspected COVID-19 cases were not reconciled with the EAC. Therefore, data that was planned for the EAC to reconcile was not available for efficacy analysis and data could not be reported for the outcome measure.
Secondary
Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs)
An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate.
Time frame: Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 0 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 2.0 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 0.3 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) | 0 percentage of participants |
Secondary
Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly or birth defect.
Time frame: Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 2.6 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 1.4 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 6.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 3.9 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 0.7 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) | 1.3 percentage of participants |
Secondary
Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Participants were provided a diary to record the solicited systemic AEs. The solicited AEs were recorded for 7 days after each dose.
Time frame: 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35)
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 72.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 83.7 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 70.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 56.9 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 31.6 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs) | 31.5 percentage of participants |
Secondary
Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions
Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration \[FDA\] Guidance for Industry, September 2007). Participants were provided a diary to record the solicited injection site reactions. Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were recorded. Injection site reactions were evaluated starting 30 minutes following the injection. The solicited injection site reactions were recorded for 7 days after each dose.
Time frame: 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35)
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 27.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 1.9 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 17.9 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 11.3 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 25.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 5.4 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 36.1 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 16.3 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 2.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 18.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 2.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 20.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 23.5 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 2.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 3.9 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 7.8 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 6.8 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 4.2 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 19.1 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Erythema | 6.0 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Swelling | 2.6 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions | Injection Site Pain | 21.2 percentage of participants |
Secondary
Phase 2 and 3: Percentage of Participants With Unsolicited AEs
An AE is defined as any untoward medical occurrence in a participant administered a trial intervention that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unsolicited AEs were recorded for up to 28 days after administration of dose 2.
Time frame: From first dose of study drug up to Day 56
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 74.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 85.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 74.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 62.7 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 38.8 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Unsolicited AEs | 37.1 percentage of participants |
Secondary
Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions
Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' FDA Guidance for Industry, September 2007. Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were reported. Injection site reactions were evaluated starting 30 minutes following the injection. Unsolicited injection site reactions were recorded for up to 28 days after administration of dose 2.
Time frame: From first dose of study drug up to Day 56
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 27.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 0.6 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 17.9 percentage of participants |
| Phase 2: INO-4800 Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 11.3 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 25.2 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 36.7 percentage of participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 16.3 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 2.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 18.0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 2: Placebo Dose Group 1 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 22.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 23.5 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 2.0 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 1.9 percentage of participants |
| Phase 2: Placebo Dose Group 2 | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 7.8 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 6.8 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 4.2 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 3: INO-4800 Dose Group (2.0mg Per Dosing Visit) | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 19.3 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Tenderness | 0 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Erythema | 6.0 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Swelling | 2.6 percentage of participants |
| Phase 3: Placebo Dose Group | Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions | Injection Site Pain | 21.5 percentage of participants |
Secondary
Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay
Whole blood and serum samples were collected for the cellular immunology assessment. The antigen-specific cellular immune response to INO-4800 were measured using ELISpot.
Time frame: Baseline up to Day 126
Population: Due to the early termination of the study, immunogenicity analysis that was pre-specified in the protocol was not performed in the Phase 3 segment of the study. Hence, data for this outcome measure was not collected.
Secondary
Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay
The immune responses to INO-4800 were measured using assays that included a pseudovirus-based neutralization assay.
Time frame: Baseline up to Day 126
Population: Due to the early termination of the study, immunogenicity analysis that was pre-specified in the protocol was not performed in the Phase 3 segment of the study. Hence, data for this outcome measure was not collected.
Secondary
Phase 3: Number of Participants With Death From All Causes
Time frame: Baseline up to Day 126
Population: Safety population included all participants who received at least one dose of the trial intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 2: INO-4800 Dose Group 1 | Phase 3: Number of Participants With Death From All Causes | 2 Participants |
| Phase 2: INO-4800 Dose Group 2 | Phase 3: Number of Participants With Death From All Causes | 2 Participants |
Secondary
Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Death From COVID-19 Disease
Time frame: From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126)
Population: For the Phase 3 segment, as pre-specified in the protocol, an independent EAC was to review and confirm the suspected COVID-19 cases which fulfilled the definition for virologically-confirmed COVID-19 cases. As the trial was prematurely terminated, suspected COVID-19 cases were not reconciled with the EAC. Therefore, data that was planned for the EAC to reconcile was not available for efficacy analysis and data could not be reported for the outcome measure.
Secondary
Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Non-Severe COVID-19 Disease
The efficacy of INO-4800 in the prevention of COVID-19 disease was evaluated according to the degrees of COVID-19 disease severity in participants. Participants were confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. The case definition of severe COVID-19 was participants with COVID-19 having clinical signs at rest indicative of severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to an intensive care unit, or death. The case definition for non-severe COVID-19 was participants with confirmed COVID-19, and which did not meet the case definition of severe COVID-19.
Time frame: From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126)
Population: For the Phase 3 segment, as pre-specified in the protocol, an independent EAC was to review and confirm the suspected COVID-19 cases which fulfilled the definition for virologically-confirmed COVID-19 cases. As the trial was prematurely terminated, suspected COVID-19 cases were not reconciled with the EAC. Therefore, data that was planned for the EAC to reconcile was not available for efficacy analysis and data could not be reported for the outcome measure.
Secondary
Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Severe COVID-19 Disease
The efficacy of INO-4800 in the prevention of COVID-19 disease was evaluated according to the degrees of COVID-19 disease severity in participants. Participants were confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. The case definition of severe COVID-19 was participants with COVID-19 having clinical signs at rest indicative of severe systemic illness, respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to an intensive care unit, or death.
Time frame: From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126)
Population: For the Phase 3 segment, as pre-specified in the protocol, an independent EAC was to review and confirm the suspected COVID-19 cases which fulfilled the definition for virologically-confirmed COVID-19 cases. As the trial was prematurely terminated, suspected COVID-19 cases were not reconciled with the EAC. Therefore, data that was planned for the EAC to reconcile was not available for efficacy analysis and data could not be reported for the outcome measure.
Secondary
Phase 3: Percentage of Participants (SARS-CoV-2 Seropositive at Baseline) With Virologically-Confirmed SARS-CoV-2 COVID-19 Disease
Participants were virologically-confirmed cases of COVID-19, if tested positive by SARS-CoV-2 RT-PCR assay, with symptoms like fever (temperature of 100.4ºF/38.0ºC or higher), chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, vomiting, diarrhoea. Participants with prior exposure to COVID-19 at baseline were considered for the analysis.
Time frame: From 14 days after completion of the 2-dose regimen up to 3 months post-dose 2 (i.e. Day 42 up to Day 126)
Population: For the Phase 3 segment, as pre-specified in the protocol, an independent EAC was to review and confirm the suspected COVID-19 cases which fulfilled the definition for virologically-confirmed COVID-19 cases. As the trial was prematurely terminated, suspected COVID-19 cases were not reconciled with the EAC. Therefore, data that was planned for the EAC to reconcile was not available for efficacy analysis and data could not be reported for the outcome measure.