Clinical trial NCT04642638: Safety, Immunogenicity, and Efficacy of INO-4800 for COVID-19 in Adults at High Risk of SARS-CoV-2 Exposure
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Coronavirus Infection
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
COVID-19 Disease
Keywords: DNA vaccine
Electroporation
Healthy
COVID-19
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Advaccine (Suzhou) Biopharmaceuticals Co., Ltd.
First posted: 2020-11-24
Enrollment: 1307
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay
timeFrame: Baseline up to Week 6
measure: Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay
timeFrame: Baseline up to Week 6
measure: Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Virologically-confirmed COVID-19 Disease
timeFrame: 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)
Secondary outcomes:
measure: Phase 2 and 3: Percentage of Participants With Solicited Injection Site Reactions
timeFrame: 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35)
measure: Phase 2 and 3: Percentage of Participants With Unsolicited Injection Site Reactions
timeFrame: From first dose of study drug up to Day 56
measure: Phase 2 and 3: Percentage of Participants With Solicited Adverse Events (AEs)
timeFrame: 7 days following each dose: Day 0 (Days 0 to Day 7) and Day 28 (Days 28 to Day 35)
measure: Phase 2 and 3: Percentage of Participants With Unsolicited AEs
timeFrame: From first dose of study drug up to Day 56
measure: Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126
measure: Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Phase 2: From first dose of study drug up to Day 393; Phase 3: From first dose of study drug up to Day 126
measure: Phase 3: Number of Participants With Death From All Causes
timeFrame: Baseline up to Day 126
measure: Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Non-Severe COVID-19 Disease
timeFrame: 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)
measure: Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Severe COVID-19 Disease
timeFrame: 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)
measure: Phase 3: Percentage of Participants (SARS-CoV-2 Seronegative at Baseline) With Death From COVID-19 Disease
timeFrame: 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)
measure: Phase 3: Percentage of Participants (SARS-CoV-2 Seropositive at Baseline) With Virologically-Confirmed SARS-CoV-2 COVID-19 Disease
timeFrame: 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)
measure: Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay
timeFrame: Baseline up to Day 126
measure: Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay
timeFrame: Baseline up to Day 126
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc - Phoenix Southeast
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Synexus Clinical Research
state: Arizona
city: Tempe
country: United States
facility: AMR Tempe
state: Arizona
city: San Diego
country: United States
facility: Optimal Research, LLC
state: California
city: Coral Gables
country: United States
facility: AMR South Florida
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc
state: Florida
city: Lexington
country: United States
facility: AMR Lexington
state: Kentucky
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research
state: Maryland
city: Detroit
country: United States
facility: Ascension St. John Hospital
state: Michigan
city: Kansas City
country: United States
facility: AMR Kansas City
state: Missouri
city: Las Vegas
country: United States
facility: AMR, Clinical Research Consortium- Las Vegas
state: Nevada
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Barranquilla
country: Colombia
facility: Centro de Investigacion Medico Asistencial S.A.S
state: Atlántico
city: Barranquilla
country: Colombia
facility: Clinica de la Costa LTDA
state: Atlántico
city: Barranquilla
country: Colombia
facility: Corazon IPS S.A.S
state: Atlántico
city: Barranquilla
country: Colombia
facility: Ips Centro Cientifico Asistencial Sas
state: Atlántico
city: Pereira
country: Colombia
facility: Centro de Investigaciones Clinicas IPS Cardiomet Pereira
state: Risaralda
city: Guadalajara
country: Mexico
facility: BRCR Global Mexico
state: Jalisco
city: Monterrey
country: Mexico
facility: Eukarya Pharmasite SC
state: Nuevo Leon
city: San Juan del Río
country: Mexico
facility: Unidad de Medicina Especializada SMA
state: Querétaro
city: Mexico City
country: Mexico
facility: Clinstile, SA de CV
city: Querétaro
country: Mexico
facility: SMIQ, S. de R. L. de C.V.
city: Veracruz
country: Mexico
facility: FAICIC S. de R.L. de C.V.
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jose Suaya
role: STUDY_DIRECTOR
References: