Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
Conditions
Keywords
Healthy, Coronavirus
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.
Interventions
DRUGINO-4700
INO-4700 was administered ID.
DRUGPlacebo
Sterile saline sodium citrate (SSC) buffer (SSC-0001) was administered ID.
DEVICECELLECTRA™ 2000
EP using the CELLECTRA™ 2000 device was administered following ID drug administration
Sponsors
Inovio Pharmaceuticals
Coalition for Epidemic Preparedness Innovations
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Graded by Severity, and Treatment-related AEs | From the first dose of the study drug up to the end of the study (up to 48.7 weeks) | 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). |
| Part 1: Percentage of Participants With Injection Site Reactions | From the first dose of the study drug up to the end of the study (up to 48.7 weeks) | 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. |
| Part 1: Percentage of Participants With Adverse Events of Special Interest (AESIs) | From Screening to the end of the study (up to 48.7 weeks) | 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. |
| Part 1: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody at Week 6 | 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. |
| Part 1: Geometric Mean Fold Rise (GMFR) of INO-4700 Antigen Specific Binding Antibody at Week 6 | 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. |
| Part 1: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody at Week 10 | 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. |
| Part 1: Geometric Mean Fold Rise (GMFR) of INO-4700 Antigen Specific Binding Antibody at Week 10 | 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. |
| Part 1: Percentage Neutralizing Antibody Responders at Week 6 | 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. |
| Part 1: Percentage Neutralizing Antibody Responders at Week 10 | 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. |
| Part 1: Percentage of Antigen Specific Cellular Immune Responders at Week 6 | 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. |
| Part 1: Percentage of Antigen Specific Cellular Immune Responders at Week 10 | 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. |
| Part 2: Percentage of Participants With Adverse Events | From the first dose of the study drug up to the end of the study (up to 68 weeks) | 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. |
| Part 2: Percentage of Participants With Injection Site Reactions | From the first dose of the study up to the end of the study (up to 68 weeks) | 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. |
| Part 2: Percentage of Participants With Adverse Events of Special Interest (AESIs) | From Screening up to the end of the study (up to 68 weeks) | 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. |
| Part 2: Geometric Mean Concentration (GMC) of INO-4700 Antigen Specific Binding Antibody | At Week 12 | 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. |
| Part 2: Percentage Neutralizing Antibody Responders | At Week 12 | 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. |
| Part 2: Percentage of Antigen Specific Cellular Immune Responders | At Week 12 | 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). |
Countries
Jordan, Kenya, Lebanon
Contacts
STUDY_DIRECTORBonaventure Orizu, MD
Inovio Pharmaceuticals
Participant flow
Recruitment details
Healthy adult volunteers were enrolled at 6 study sites between 21 June 2021 and 19 January 2023.
Pre-assignment details
This study was planned for two parts i.e., Part 1 and Part 2. A total of 218 participants were screened for Part 1 of the study, out of which 192 participants were enrolled. Part 1 was to select the optimal dose for Part 2. However, none of the dose groups studied in Part 1 met the immunological criteria for advancement to Part 2. Consequently, the study ended at the conclusion of Part 1. The data is reported only for Part 1.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 34.2 years STANDARD_DEVIATION 9.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 172 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 33 | 0 / 32 | 0 / 32 | 0 / 31 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 6 / 32 | 10 / 33 | 11 / 32 | 8 / 32 | 11 / 31 | 2 / 8 | 6 / 8 | 2 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 32 | 1 / 33 | 0 / 32 | 1 / 32 | 0 / 31 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
None listed