| Protocol No: | ECCT/20/12/02 | Date of Protocol: | 23-03-2020 |
| Study Title: |
Study to Evaluate the Safety, Tolerability and Immunogenicity of INO-4700 for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Healthy Volunteers
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| Study Objectives: | Primary Obejectives: Evaluate the tolerability and safety of INO-4700 administered by ID injection followed by EP in healthy adult volunteers Evaluate the cellular (T cell) and humoral immune response to INO-4700 administered by ID injection followed by EP for identification and confirmation of an optimal dose and regimen Evaluate selected optimal dose for safety and immunogenicity Exploratory Objectives: Evaluate the expanded immunological profile by assessing both T and B cell immune responses Evaluate the cellular (T cell) and humoral immune response to INO-4700 administered by ID injection followed by EP for impact of boosting with a third dose
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| Laymans Summary: |
The vaccine in this clinical trial is an investigational product called INO-4700. INO-4700 will be given with an investigational device, CELLECTRA™ 2000. The CELLECTRATM 2000 device is used to deliver four (4) brief pulses of electricity (called electroporation, or “EP”) to get more of the investigational product into the skin cells. INO-4700 is being developed to protect humans from an illness called Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV) infection. MERS-CoV is an animal-borne (found in Arabian (one hump) camels) infection caused by a virus that is spread from animals to humans. Once humans are infected with this virus, it can also spread from human to human by direct contact. MERS-CoV causes serious respiratory illness in humans.
The purpose of this clinical trial is to:
• Test the safety and tolerability (level of discomfort) of the vaccine and the device in healthy volunteers
• Test the effect of the vaccine and the device on the immune system
• Select the most favorable dose
Approximately 542 healthy volunteers will participate in this clinical trial. Subjects will be in the study for either 48 weeks or 68 weeks. Subjects will either receive INO-4700 or placebo (a product without medication).
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| Abstract of Study: | Background: The lack of available therapy in conjunction with increasing numbers of global cases indicates that MERS-CoV infection remains a serious unmet medical need. Due to cross-species infection, both human and animal outbreaks are possible. Appropriate measures to prevent, control and treat existing and future infections are needed. The hypothesis of this study is that a selected optimal dose of INO-4700 delivered intradermally (ID) followed by electroporation (EP) using CELLECTRATM 2000 in healthy volunteers will be well tolerated, exhibit an acceptable safety profile and result in generation of immune responses to MERS-CoV. Methods: This is a Phase 2a, randomized, blinded, placebo-controlled, multi-center trial in healthy adult volunteers. Approximately 542 participants will be evaluated across two (2) parts of this study. In Part 1, 192 participants ages 18-50 years will be assessed through five (5) dose levels and regimens. INO-4700 or placebo (SSC-0001) will be administered ID followed immediately by EP. Participants will be randomized to receive either INO-4700 (160 subjects) or placebo (32 subjects) via one or two injections, followed by EP, at weeks 0 and 4 or weeks 0 and 8. Upon completion of the Week 10 visit, Part 1 will be unblinded in order to allow for one regimen to be selected for advancement into Part 2. The Study Group with an optimal immune response, an acceptable safety profile and tolerant dosing regimen by Week 10 will be selected. All Part 1 participants will be followed for 48 weeks from the Da y 0 dosing. In Part 2, approximately 350 participants ages 18 and older will be evaluated across one (1) dose level and regimen. Part 2 of the study is divided into two parts, Part 2A and 2B. In Part 2A, participants will be randomized to receive INO-4700 (300 participants) or placebo (50 participants). In Part 2B, the first 200 participants randomized to receive INO-4700 in Part 2A will receive a third dose of either INO-4700 or placebo at Week 48. Similarly, in Part 2B, the first 25 participants randomized to receive placebo in Part 2A will receive a third dose of placebo at Week 48. These first 225 participants will be followed for 68 weeks from the Day 0 dosing. All remaining 125 participants will be followed for 48 weeks from the Day 0 dosing. Adverse events will be collected at every visit and safety samples and immunology blood samples will be drawn throughout the study. All adverse events, regardless of relationship, will be collected from the time of consent to 12 weeks from Day 0. Only related adverse events, adverse events of special interest and serious adverse events will be collected thereafter.
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| 1 | 1. Exclusion Criteria and Restrictions related to receipt of other vaccinations have been updated due to anticipated availability of the COVID-19 vaccine. Previously, participants were not to receive other vaccinations within 2 weeks before or after dosing. This has been amended to prohibit receipt of other vaccinations from 30 days prior to Day 0 until completion of the study visit occurring 2 weeks after the second dose of investigational product (i.e., the Week 6 visit if dosed at Week 4 and the Week 10 visit if dosed at Week 8). For Part 2B, receipt of other vaccinations is also prohibited from 2 weeks prior to the Week 48 visit through the Week 50 visit. – Section 4.2 exclusion Criteria, page 33 of 78 the track changes protocol. 2. Exclusion criteria has been updated to no longer prohibit prior receipt of an investigational vaccine product for SARS. - Section 4.2 exclusion Criteria, page 33 of 78 3. The collection of adverse events has been updated so that all adverse events will be collected throughout the study, rather than only collecting related adverse events, adverse events of special interest and serious adverse events subsequent to the Week 12 visit. This will allow for improved safety assessment after the Part 2, Week 48 booster dose. Section 6.4.4, Adverse Events, page 49 0f 78 4. The timeline for contraception requirements has been updated so that contraception must be used from screening until 3 months following last dose, rather than from screening to 1 month following last dose, for consistency across the Sponsor’s infectious disease programs. Exclusion criteria a was also updated accordingly. Section 6.4.8, restriction, page 51 of 78 5. At the Principal Investigator’s discretion, collection of the screening immunology samples may be postponed and collected along with the Day 0 samples. This may decrease the unnecessary collection of immunology samples from participants that fail screening. -Immunogenicity assessment, page 14 of 78 6. The following changes have been made to the visit procedures: a. Week 2, Part 1 and Part 2: Collection of immunology samples has been removed. Based on experience across DNA vaccine studies, the week 2 sample is not needed to adequately assess immune response. Section 6.1.2.2 Week 2, page 41 of 78 b. Week 12, Part 1 and Part 2 (Day 0 & Week 8): Collection of immunology samples has been removed. Based on experience across DNA vaccine studies, the week 2 sample is not needed to adequately assess immune response. These visits have been updated to follow-up phone calls for collection of adverse events. -Section 6.1.2.7, week 12, page 44 of 78 c. Week 8, Part 2 (Day 0 & Week 8): Collection of immunology samples has been added. This will allow for better assessment of immune response after one dose. Section 3.6, Immunogenicity Assessment, page 32 of 78 7. Applicable footnotes for Tables 4, 5 and 6 have been updated to reflect whole blood collection in 4 x 8.0 mL (32 mL) Cell Preparation Tubes (CPT) rather than 4 x 8.5 mL (34 mL) Acid Citrate Dextrose (ACD) tubes. A total of 64 mL will be collected prior to first dose, rather than 68 mL. Page 19 to 22, Table 4,5 and 6 8. The Exploratory Objectives, Exploratory Endpoints and Statistical Analysis Plan have been updated to include evaluation of humoral immune response of MERS-CoV spike protein and cross reactivity to other coronavirus spike proteins. – page31 of 78 of the protocol, exploratory Objectives, and study endpoint |