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

Sponsor

Inovio Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04642638

Collaborator

Advaccine (Suzhou) Biopharmaceuticals Co., Ltd. (Industry)

7,517

Enrollment

Locations

Arms

26.1

Anticipated Duration (Months)

278.4

Patients Per Site

10.7

Patients Per Site Per Month

Study Details

Study Description

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 COVID-19 in participants at high risk of exposure to 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.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Infection Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) COVID-19 Disease	Drug: INO-4800 Device: CELLECTRA® 2000 Drug: Placebo Device: CELLECTRA® 2000	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

7517 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Nov 30, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2: INO-4800 Dose Group 1 Participants will receive one intradermal (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 INO-4800 will be administered ID on Day 0 and Day 28. Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of INO-4800 on Day 0 and Day 28.
Experimental: Phase 2: INO-4800 Dose Group 2 Participants will receive 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 INO-4800 will be administered ID on Day 0 and Day 28. Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of INO-4800 on Day 0 and Day 28.
Placebo Comparator: Phase 2: Placebo Dose Group 1 Participants will receive one ID injection of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.	Drug: Placebo Sterile saline sodium citrate (SSC) buffer (SSC-0001) will be administered ID on Day 0 and Day 28. Other Names: SSC-0001 Placebo for INO-4800 Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of sterile saline sodium citrate (SSC) buffer (SSC-0001) on Day 0 and Day 28.
Placebo Comparator: Phase 2: Placebo Dose Group 2 Participants will receive two ID injections of placebo followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.	Drug: Placebo Sterile saline sodium citrate (SSC) buffer (SSC-0001) will be administered ID on Day 0 and Day 28. Other Names: SSC-0001 Placebo for INO-4800 Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of sterile saline sodium citrate (SSC) buffer (SSC-0001) on Day 0 and Day 28.
Experimental: Phase 3: INO-4800 Dose Group (2.0mg per dosing visit) Participants will receive 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 INO-4800 will be administered ID on Day 0 and Day 28. Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of INO-4800 on Day 0 and Day 28.
Placebo Comparator: Phase 3: Placebo Dose Group Participants will receive two ID injections of placebo per dosing visit, each followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.	Drug: Placebo Sterile saline sodium citrate (SSC) buffer (SSC-0001) will be administered ID on Day 0 and Day 28. Other Names: SSC-0001 Placebo for INO-4800 Device: CELLECTRA® 2000 EP using the CELLECTRA® 2000 device will be administered following ID delivery of sterile saline sodium citrate (SSC) buffer (SSC-0001) on Day 0 and Day 28.

Outcome Measures

Primary Outcome Measures

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 Day 393]
Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay [Baseline up to Day 393]
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 12 months post-dose 2 (i.e. Day 42 up to Day 393)]

Secondary Outcome Measures

Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Injection Site Reactions [From time of consent up to 28 days post-dose 2 (up to Day 56)]
Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Systemic Adverse Events (AEs) [From time of consent up to 28 days post-dose 2 (up to Day 56)]
Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs) [Baseline up to Day 393]
Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) [Baseline up to Day 393]
Phase 3: Percentage of Participants With Death From All Causes [Baseline up to Day 393]
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 12 months post-dose 2 (i.e. Day 42 up to Day 393)]
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 12 months post-dose 2 (i.e. Day 42 up to Day 393)]
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 12 months post-dose 2 (i.e. Day 42 up to Day 393)]
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 12 months post-dose 2 (i.e. Day 42 up to Day 393)]
Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay [Baseline up to Day 393]
Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay [Baseline up to Day 393]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 HIV based on a 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Synexus Clinical Research US, Inc - Phoenix Southeast	Chandler	Arizona	United States	85224
2	Central Phoenix Synexus Clinical Research	Phoenix	Arizona	United States	85020
3	AMR Tempe	Tempe	Arizona	United States	85283
4	Optimal Research, LLC	San Diego	California	United States	92108
5	AMR South Florida	Coral Gables	Florida	United States	33134
6	Clinical Research Trials of Florida, Inc	Tampa	Florida	United States	33607
7	AMR Lexington	Lexington	Kentucky	United States	40509
8	Walter Reed Army Institute of Research	Silver Spring	Maryland	United States	20910
9	Ascension St. John Hospital	Detroit	Michigan	United States	48236
10	AMR Kansas City	Kansas City	Missouri	United States	64114
11	AMR, Clinical Research Consortium- Las Vegas	Las Vegas	Nevada	United States	89119
12	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
13	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
14	Tekton Research	San Antonio	Texas	United States	78229
15	DM Clinical Research	Tomball	Texas	United States	78229
16	Advanced Clinical Research	West Jordan	Utah	United States	84088
17	Centro de Investigacion Medico Asistencial S.A.S	Barranquilla	Atlántico	Colombia	800001
18	Clinica de la Costa LTDA	Barranquilla	Atlántico	Colombia	80002
19	Corazon IPS S.A.S	Barranquilla	Atlántico	Colombia	80020
20	Ips Centro Cientifico Asistencial Sas	Barranquilla	Atlántico	Colombia	80020
21	Centro de Investigaciones Clinicas IPS Cardiomet Pereira	Pereira	Risaralda	Colombia	660003
22	BRCR Global Mexico	Guadalajara	Jalisco	Mexico	44600
23	Eukarya Pharmasite SC	Monterrey	Nuevo Leon	Mexico	64718
24	Unidad de Medicina Especializada SMA	San Juan del Río	Querétaro	Mexico	76800
25	Clinstile, SA de CV	Mexico City		Mexico	06700
26	SMIQ, S. de R. L. de C.V.	Querétaro		Mexico	76070
27	FAICIC S. de R.L. de C.V.	Veracruz		Mexico	91900