Phase 2/3 Randomized, Blinded, Placebo-Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of INO-4800, a Prophylactic Vaccine Against COVID-19 Disease, Administered Intradermally Followed by Electroporation in Adults at High Risk of SARS-CoV-2 Exposure
Overview
- Phase
- Phase 2
- Intervention
- INO-4800
- Conditions
- Coronavirus Infection
- Sponsor
- Inovio Pharmaceuticals
- Enrollment
- 1307
- Locations
- 27
- Primary Endpoint
- Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Virologically-confirmed COVID-19 Disease
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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).
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
- •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
Arms & Interventions
Phase 2: INO-4800 Dose Group 2
Participants received two 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.
Intervention: INO-4800
Phase 2: INO-4800 Dose Group 1
Participants received one ID injection of 1.0 milligram (mg) of INO-4800 followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.
Intervention: INO-4800
Phase 2: INO-4800 Dose Group 1
Participants received one ID injection of 1.0 milligram (mg) of INO-4800 followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.
Intervention: CELLECTRA® 2000
Phase 2: INO-4800 Dose Group 2
Participants received two 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.
Intervention: CELLECTRA® 2000
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.
Intervention: Placebo
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.
Intervention: CELLECTRA® 2000
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.
Intervention: Placebo
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.
Intervention: CELLECTRA® 2000
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.
Intervention: INO-4800
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.
Intervention: CELLECTRA® 2000
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.
Intervention: Placebo
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.
Intervention: CELLECTRA® 2000
Outcomes
Primary Outcomes
Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Virologically-confirmed 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)
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.
Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions(From first dose of study drug up to Day 56)
- 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))
- Phase 2 and 3: Percentage of Participants With Unsolicited AEs(From first dose of study drug up to Day 56)
- Phase 3: Number of Participants With Death From All Causes(Baseline up to Day 126)
- 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))
- 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)
- 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)
- 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))
- 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))
- 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))
- Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay(Baseline up to Day 126)
- Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay(Baseline up to Day 126)