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

Inovio Pharmaceuticals192 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

192

Conditions

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Interventions

INO-4700DRUG

INO-4700 was administered ID.

PlaceboDRUG

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

CELLECTRA™ 2000DEVICE

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

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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. Key Exclusion Criteria: * 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.

Locations (6)

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

Irbid, Jordan

Pharmaceutical Research Center / Jordan University of Science and Technology

Irbid, Jordan

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

Kericho, Kenya

Ahero Clincal Trials Unit

Kisumu, Kenya

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 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)

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

Data from ClinicalTrials.gov

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CELLECTRA™ 2000DEVICE

CELLECTRA™ 2000

American University of Beirut Medical Center

Beirut, Lebanon

Hammoud Hospital University Medical Center

Saida, Lebanon

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.

Time frame: 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.

Time frame: At Week 6

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

Time frame: At Week 10

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

Time frame: 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.

Time frame: At Week 6

Part 1: Percentage Neutralizing Antibody Responders at Week 10

Time frame: 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.

Time frame: At Week 6

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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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).

Time frame: At Week 12