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

• ClinicalTrials.gov Identifier: NCT04642638
• Recruitment Status: Terminated
• First Posted: November 24, 2020
• Last Update Posted: December 16, 2022
• Sponsor: Inovio Pharmaceuticals
• Collaborator: Advaccine (Suzhou) Biopharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Tracking Information

• First Submitted Date: November 23, 2020
• First Posted Date: November 24, 2020
• Last Update Posted Date: December 16, 2022
• Actual Study Start Date: November 30, 2020
• Actual Primary Completion Date: September 13, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 18, 2021)

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

Original Primary Outcome Measures (submitted: November 23, 2020)

• 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 Day 393 ]
• Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Percentage of Participants With Virologically-confirmed COVID-19 Disease [ Time Frame: 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) ]

Current Secondary Outcome Measures (submitted: October 18, 2021)

• Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Injection Site Reactions [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline up to Day 393 ]
• Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Percentage of Participants With Death From All Causes [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Percentage of Participants, (SARS-CoV-2 seronegative at baseline), With Non-Severe COVID-19 Disease [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay [ Time Frame: Baseline up to Day 393 ]

Original Secondary Outcome Measures (submitted: November 23, 2020)

• Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Injection Site Reactions [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline up to Day 393 ]
• Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs) [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Percentage of Participants With Death From All Causes [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Percentage of Participants With Non-Severe COVID-19 Disease [ Time Frame: 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 With Severe COVID-19 Disease [ Time Frame: 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 With Death From COVID-19 Disease [ Time Frame: 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 With Virologically-Confirmed SARS-CoV-2 Infections [ Time Frame: 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: Days to Symptom Resolution in Participants With COVID-19 Disease [ Time Frame: 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 [ Time Frame: Baseline up to Day 393 ]
• Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay [ Time Frame: Baseline up to Day 393 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

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

Intervention

• 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.
• 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.

Study Arms

• 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.
  Interventions:

  • Drug: INO-4800
  • Device: CELLECTRA® 2000
• 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.
  Interventions:

  • Drug: INO-4800
  • Device: CELLECTRA® 2000
• 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.
  Interventions:

  • Drug: Placebo
  • Device: CELLECTRA® 2000
• 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.
  Interventions:

  • Drug: Placebo
  • Device: CELLECTRA® 2000
• 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.
  Interventions:

  • Drug: INO-4800
  • Device: CELLECTRA® 2000
• 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.
  Interventions:

  • Drug: Placebo
  • Device: CELLECTRA® 2000

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 11, 2022): 1308
• Original Estimated Enrollment (submitted: November 23, 2020): 6578
• Actual Study Completion Date: September 13, 2022
• Actual Primary Completion Date: September 13, 2022 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Colombia, Mexico, United States
• Removed Location Countries: Brazil, Philippines

Administrative Information

• NCT Number: NCT04642638
• Other Study ID Numbers: COVID19-311; INNOVATE ( Other Identifier: Inovio INO-4800 Vaccine Trial for Efficacy ); WHO UTN: U1111-1266-9952 ( Other Identifier: World Health Organization (WHO) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data dictionaries and all collected IPD will be stripped of identifiers and may be made available upon request.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (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.

• Current Responsible Party: Inovio Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Inovio Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Advaccine (Suzhou) Biopharmaceuticals Co., Ltd.

Investigators

• Study Director: Bonaventure Orizu, MD; Inovio Pharmaceuticals

• PRS Account: Inovio Pharmaceuticals
• Verification Date: December 2022