Safety, Tolerability and Immunogenicity of INO-4700 for MERS-CoV in Healthy Volunteers

NCT04588428 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: MERS-201
• Study Type: interventional
• Target: 192
• Locations: 3 countries
• Sites: 6

Brief Summary

The purpose of this Phase 2a, randomized, blinded, placebo-controlled, multi-center study is to evaluate the safety, tolerability and immunogenicity of INO-4700 administered by intradermal (ID) injection followed by electroporation (EP) using the CELLECTRA™ 2000 device in healthy adult volunteers for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. This study was divided into 2 parts: Part 1- dose finding stage and Part 2- dose expansion stage.

Conditions

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Keywords

Healthy; Coronavirus

Outcome Measures

Primary Outcomes (17)

• Part 1: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Graded by Severity, and Treatment-related AEs

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with treatment. TEAEs: AEs with onset after administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. TEAEs were graded based on the Toxicity Grading Scale for Healthy Adult \& Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Food and Drug Administration \[FDA\] Guidance for Industry), as Grade 1: No interference with activity, Grade 2: Some interference with activity, Grade 3: Prevents daily activity/requires medical intervention \& Grade 4: Emergency room visit/hospitalization. A causally related AE is one judged by the Investigator to have a possible, probable, or definite relationship to the administration of an investigational product (IP).

  From the first dose of the study drug up to the end of the study (up to 48.7 weeks)

• Part 1: Percentage of Participants With Injection Site Reactions

  Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' FDA Guidance for Industry, September 2007. Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were recorded. Injection site reactions were evaluated starting 30 minutes following the injection.

  From the first dose of the study drug up to the end of the study (up to 48.7 weeks)

• Part 1: Percentage of Participants With Adverse Events of Special Interest (AESIs)

  An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Principal Investigator to the Sponsor can be appropriate.

  From Screening to the end of the study (up to 48.7 weeks)

• Part 1: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody at Week 6

  Whole blood and serum samples were collected for the cellular immunology assessment. MERS receptor binding domain (RBD) immunoglobulin G (IgG) concentrations in response to administration of INO-4700 in combination with EP were reported as the GMC.

  At Week 6

• Part 1: Geometric Mean Fold Rise (GMFR) of INO-4700 Antigen Specific Binding Antibody at Week 6

  Whole blood and serum samples were collected for the cellular immunology assessment. MERS RBD IgG concentrations in response to administration of INO-4700 in combination with EP were reported as the GMFR.

  At Week 6

• Part 1: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody at Week 10

  Whole blood and serum samples were collected for the cellular immunology assessment. MERS RBD IgG concentrations in response to administration of INO-4700 in combination with EP were reported as the GMC.

  At Week 10

• Part 1: Geometric Mean Fold Rise (GMFR) of INO-4700 Antigen Specific Binding Antibody at Week 10

  Whole blood and serum samples were collected for the cellular immunology assessment. MERS RBD IgG concentrations in response to administration of INO-4700 in combination with EP were reported as the GMFR.

  At Week 10

• Part 1: Percentage Neutralizing Antibody Responders at Week 6

  The immune responses to INO-4700 were measured using assays that included a pseudovirus-based neutralization assay. Immunology blood samples were collected at serial time points. A MERS pseudovirus neutralizing antibody responder was defined as a participant with a sample post-treatment 50% inhibitory dose (ID50) that was \>20. Percentage responders were calculated based on number of responders at specified visit divided by number of participants evaluable at specified visit.

  At Week 6

• Part 1: Percentage Neutralizing Antibody Responders at Week 10

  The immune responses to INO-4700 were measured using assays that included a pseudovirus-based neutralization assay. Immunology blood samples were collected at serial time points. A MERS pseudovirus neutralizing antibody responder was defined as a participant with a sample post-treatment 50% inhibitory dose (ID50) that was \>20. Percentage responders were calculated based on number of responders at specified visit divided by number of participants evaluable at specified visit.

  At Week 10

• Part 1: Percentage of Antigen Specific Cellular Immune Responders at Week 6

  Assessments of cellular immune responses to INO-4700 were performed using the immune response measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay on peripheral blood mononuclear cells (PBMCs). A MERS spike ELISpot responder was defined as a participant with a post-treatment level that was \> baseline + 2 standard deviations of replicate. Percentage responders were calculated as on number of responders at specified visit divided by number of participants evaluable at specified visit.

  At Week 6

• Part 1: Percentage of Antigen Specific Cellular Immune Responders at Week 10

  Assessments of cellular immune responses to INO-4700 were performed using the immune response measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay on peripheral blood mononuclear cells (PBMCs). A MERS spike ELISpot responder was defined as a participant with a post-treatment level that was \> baseline + 2 standard deviations of replicate. Percentage responders were calculated as on number of responders at specified visit divided by number of participants evaluable at specified visit.

  At Week 10

• Part 2: Percentage of Participants With Adverse Events

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have causal relationship with treatment.

  From the first dose of the study drug up to the end of the study (up to 68 weeks)

• Part 2: Percentage of Participants With Injection Site Reactions

  Reactions arising from the injectable product administration procedure were reported as injection site reactions. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (FDA Guidance for Industry, September 2007). Local reactions to the injectable product such as pain, tenderness, erythema/redness, and induration/swelling were recorded. Injection site reactions were evaluated starting 30 minutes following the injection.

  From the first dose of the study up to the end of the study (up to 68 weeks)

• Part 2: Percentage of Participants With Adverse Events of Special Interest (AESIs)

  An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Principal Investigator to the Sponsor can be appropriate. These included respiratory distress syndrome, pneumonia, neurologic, hematologic, immunologic, and other events (including local or systemic SAEs, acute renal failure, SARS-CoV-2 infection, or death). In addition, anxiety and pain related to the EP procedure were monitored.

  From Screening up to the end of the study (up to 68 weeks)

• Part 2: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody

  Whole blood and serum samples were collected for the cellular immunology assessment. MERS receptor binding domain (RBD) immunoglobulin G (IgG) concentrations in response to administration of INO-4700 in combination were to be assessed.

  At Week 12

• Part 2: Percentage Neutralizing Antibody Responders

  The immune responses to INO-4700 were to be measured using assays that included a pseudovirus-based neutralization assay. Immunology blood samples were to be collected at serial timepoints.

  At Week 12

• Part 2: Percentage of Antigen Specific Cellular Immune Responders

  Assessments of cellular immune responses to INO-4700 were to be performed using the immune response measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay on peripheral blood mononuclear cells (PBMCs).

  At Week 12

Study Arms (10)

Part 1: INO-4700 Group A

EXPERIMENTAL

Participants received one intradermal (ID) injection of 0.6 milligram (mg) of INO-4700 followed by electroporation (EP) using the CELLECTRA™ 2000 device on Day 0 and Week 4.

Drug: INO-4700; Device: CELLECTRA™ 2000

Part 1: INO-4700 Group B

EXPERIMENTAL

Participants received one ID injection of 1.0 mg of INO-4700 followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 4.

Drug: INO-4700; Device: CELLECTRA™ 2000

Part 1: INO-4700 Group C

EXPERIMENTAL

Participants received one ID injection of 1.0 mg of INO-4700 followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 8.

Drug: INO-4700; Device: CELLECTRA™ 2000

Part 1: INO-4700 Group D

EXPERIMENTAL

Participants received two ID injections (in an acceptable location on two different limbs) of 0.5 mg each of INO-4700 followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 8.

Drug: INO-4700; Device: CELLECTRA™ 2000

Part 1: INO-4700 Group E

EXPERIMENTAL

Participants received two ID injections (in an acceptable location on two different limbs) of 1.0 mg each of INO-4700 followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 4.

Drug: INO-4700; Device: CELLECTRA™ 2000

Part 1: Placebo Group F

PLACEBO COMPARATOR

Participants received one ID injection of placebo followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 4.

Drug: Placebo; Device: CELLECTRA™ 2000

Part 1: Placebo Group G

PLACEBO COMPARATOR

Participants received one ID injection of placebo followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 8.

Drug: Placebo; Device: CELLECTRA™ 2000

Part 1: Placebo Group H

PLACEBO COMPARATOR

Participants received two ID injections (in an acceptable location on two different limbs) of placebo followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 8.

Drug: Placebo; Device: CELLECTRA™ 2000

Part 1: Placebo Group I

PLACEBO COMPARATOR

Participants received two ID injections (in an acceptable location on two different limbs) of placebo followed by EP using the CELLECTRA™ 2000 device on Day 0 and Week 4.

Drug: Placebo; Device: CELLECTRA™ 2000

Part 2: Parts 2A and 2B

EXPERIMENTAL

Participants were planned to receive ID injection of INO-4700 based on optimal dose and regimen selection in Part 1 followed by EP using the CELLECTRA™ 2000 device on Day 0, Week 4 or Week 8 and a booster dose at Week 48 (only for Part 2B participants were planned to receive a third dose).

Drug: INO-4700; Device: CELLECTRA™ 2000

Interventions

INO-4700 DRUG

INO-4700 was administered ID.

Part 1: INO-4700 Group A; Part 1: INO-4700 Group B; Part 1: INO-4700 Group C; Part 1: INO-4700 Group D; Part 1: INO-4700 Group E

Placebo DRUG

Sterile saline sodium citrate (SSC) buffer (SSC-0001) was administered ID.

Also known as: SSC-0001

Part 1: Placebo Group F; Part 1: Placebo Group G; Part 1: Placebo Group H; Part 1: Placebo Group I

CELLECTRA™ 2000 DEVICE

EP using the CELLECTRA™ 2000 device was administered following ID drug administration

Part 1: INO-4700 Group A; Part 1: INO-4700 Group B; Part 1: INO-4700 Group C; Part 1: INO-4700 Group D; Part 1: INO-4700 Group E; Part 1: Placebo Group F; Part 1: Placebo Group G; Part 1: Placebo Group H; Part 1: Placebo Group I

Eligibility Criteria

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

You may qualify if:

• Judged to be healthy by the Investigator on the basis of medical history, physical examination and vital signs performed at Screening;
• Able and willing to comply with all study procedures;
• Screening laboratory results within normal limits;
• Negative tests for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody and Human Immunodeficiency Virus (HIV) antibody;
• Screening electrocardiogram (ECG) deemed by the Investigator as having no clinically significant findings (e.g. Wolff-Parkinson-White syndrome);
• 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.

You may not qualify if:

• Pregnant or breastfeeding, or intending to become pregnant or father children within the projected duration of the trial starting with the screening visit until 3 months following last dose;
• History of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) or chronic bronchitis;
• Currently participating in or has participated in a study with an investigational product within 30 days preceding Day 0;
• Previous receipt of any vaccine within 30 days preceding Day 0 or planning to receive any vaccine during the timeframe restricted per the protocol;
• Previous receipt of an investigational vaccine product for the prevention of MERS;
• Prior exposure to MERS-CoV or camels;
• Participants who participate in MERS-201 Part 1 cannot participate in MERS-201 Part 2;
• Fewer than two acceptable sites available for ID injection and EP considering the deltoid and anterolateral quadriceps muscles;
• Prisoner or participants who are compulsorily detained (involuntary incarceration);
• Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids) prior to dosing. Systemic corticosteroids must be discontinued at least 3 months prior to first dose;
• Reported active drug or alcohol or substance abuse or dependence.

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead
• Coalition for Epidemic Preparedness Innovations: collaborator

Study Sites (6)

Clinical Research Center, Irbid Specialty Hospital (CRC/ISH)

Irbid, 21110, Jordan

Location

Pharmaceutical Research Center / Jordan University of Science and Technology

Irbid, 22110, Jordan

Location

Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)

Kericho, 20200, Kenya

Location

Ahero Clincal Trials Unit

Kisumu, 40100, Kenya

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Hammoud Hospital University Medical Center

Saida, Lebanon

Location

Related Publications (1)

• Agnes JT, Marcus SA, Al-Ghraibeh SS, Al-Sweedan SA, Kosgei J, Ogutu B, Yang S, Walker KA, Orizu B, Broderick KE, Boyer J, Ramos S, Morrow MP, Kraynyak K, Sylvester AJ, Gillespie E, Liebowitz D, Humeau LM. Safety, tolerability, and immunogenicity of a DNA-based vaccine (INO-4700) against Middle East respiratory syndrome coronavirus: phase 2a study in healthy volunteers. Front Immunol. 2025 Nov 14;16:1662923. doi: 10.3389/fimmu.2025.1662923. eCollection 2025.

  PMID: 41322416 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Study Director
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4237

Study Officials

• Bonaventure Orizu, MD

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 19, 2020
• Study Start: June 21, 2021
• Primary Completion: January 19, 2023
• Study Completion: January 19, 2023
• Last Updated: January 22, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

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

JO (2); LE (2); KE (2)