Safety, Immunogenicity, and Efficacy of INO-4800 for COVID-19 in Adults at High Risk of SARS-CoV-2 Exposure

NCT04642638 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 3 other identifiers: COVID19-311INNOVATEWHO UTN: U1111-1266-9952
• Study Type: interventional
• Target: 1,307
• Locations: 3 countries
• Sites: 27

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.

Conditions

Coronavirus Infection; Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); COVID-19 Disease

Keywords

DNA vaccine; Electroporation; Healthy; COVID-19

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline up to Week 6

• 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.

  Baseline up to Week 6

• 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.

  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 (13)

• 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 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 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

Study Arms (6)

Phase 2: INO-4800 Dose Group 1

EXPERIMENTAL

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.

Drug: INO-4800; Device: CELLECTRA® 2000

Phase 2: INO-4800 Dose Group 2

EXPERIMENTAL

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.

Drug: INO-4800; Device: CELLECTRA® 2000

Phase 2: Placebo Dose Group 1

PLACEBO COMPARATOR

Participants received one ID injection of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.

Drug: Placebo; Device: CELLECTRA® 2000

Phase 2: Placebo Dose Group 2

PLACEBO COMPARATOR

Participants received 2 ID injections of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.

Drug: Placebo; Device: CELLECTRA® 2000

Phase 3: INO-4800 Dose Group (2.0mg per dosing visit)

EXPERIMENTAL

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.

Drug: INO-4800; Device: CELLECTRA® 2000

Phase 3: Placebo Dose Group

PLACEBO COMPARATOR

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.

Drug: Placebo; Device: CELLECTRA® 2000

Interventions

INO-4800 DRUG

INO-4800 was administered ID on Day 0 and Day 28.

Phase 2: INO-4800 Dose Group 1; Phase 2: INO-4800 Dose Group 2; Phase 3: INO-4800 Dose Group (2.0mg per dosing visit)

CELLECTRA® 2000 DEVICE

EP using the CELLECTRA® 2000 device was administered following ID delivery of INO-4800 on Day 0 and Day 28.

Phase 2: INO-4800 Dose Group 1; Phase 2: INO-4800 Dose Group 2; Phase 3: INO-4800 Dose Group (2.0mg per dosing visit)

Placebo DRUG

Sterile saline sodium citrate (SSC) buffer (SSC-0001) was administered ID on Day 0 and Day 28.

Also known as: SSC-0001, Placebo for INO-4800

Phase 2: Placebo Dose Group 1; Phase 2: Placebo Dose Group 2; Phase 3: Placebo Dose Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead
• Advaccine (Suzhou) Biopharmaceuticals Co., Ltd.: collaborator

Study Sites (27)

Synexus Clinical Research US, Inc - Phoenix Southeast

Chandler, Arizona, 85224, United States

Location

Central Phoenix Synexus Clinical Research

Phoenix, Arizona, 85020, United States

Location

AMR Tempe

Tempe, Arizona, 85283, United States

Location

Optimal Research, LLC

San Diego, California, 92108, United States

Location

AMR South Florida

Coral Gables, Florida, 33134, United States

Location

Clinical Research Trials of Florida, Inc

Tampa, Florida, 33607, United States

Location

AMR Lexington

Lexington, Kentucky, 40509, United States

Location

Walter Reed Army Institute of Research

Silver Spring, Maryland, 20910, United States

Location

Ascension St. John Hospital

Detroit, Michigan, 48236, United States

Location

AMR Kansas City

Kansas City, Missouri, 64114, United States

Location

AMR, Clinical Research Consortium- Las Vegas

Las Vegas, Nevada, 89119, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Tekton Research

San Antonio, Texas, 78229, United States

Location

DM Clinical Research

Tomball, Texas, 78229, United States

Location

Advanced Clinical Research

West Jordan, Utah, 84088, United States

Location

Centro de Investigacion Medico Asistencial S.A.S

Barranquilla, Atlántico, 800001, Colombia

Location

Clinica de la Costa LTDA

Barranquilla, Atlántico, 80002, Colombia

Location

Corazon IPS S.A.S

Barranquilla, Atlántico, 80020, Colombia

Location

Ips Centro Cientifico Asistencial Sas

Barranquilla, Atlántico, 80020, Colombia

Location

Centro de Investigaciones Clinicas IPS Cardiomet Pereira

Pereira, Risaralda Department, 660003, Colombia

Location

BRCR Global Mexico

Guadalajara, Jalisco, 44600, Mexico

Location

Eukarya Pharmasite SC

Monterrey, Nuevo León, 64718, Mexico

Location

Unidad de Medicina Especializada SMA

San Juan del Río, Querétaro, 76800, Mexico

Location

Clinstile, SA de CV

Mexico City, 06700, Mexico

Location

SMIQ, S. de R. L. de C.V.

Querétaro, 76070, Mexico

Location

FAICIC S. de R.L. de C.V.

Veracruz, 91900, Mexico

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

reluscovtogene ralaplasmid

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4237

Study Officials

• Jose Suaya

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: November 24, 2020
• Study Start: November 30, 2020
• Primary Completion: September 13, 2022
• Study Completion: September 13, 2022
• Last Updated: December 20, 2023
• Results First Posted: December 20, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Anonymous IPD may be shared following or during the publication of summary data. Archival data may be accessed for up to 10 years following the end of the study.
• Access Criteria: Those who request the anonymous IPD must provide a plan of study explaining how the data will be used. Requests may be sent to the Central Contact Person. Requests will be reviewed based on the potential for the planned use of the IPD for advancing scientific knowledge and theory.

Locations

ME (6); US (16); CO (5)