Safety and Immunogenicity of the Candidate Vaccine MVA-MERS-S_DF-1 Against MERS

Study Overview
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Brief Summary
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The study will be a two center, randomized, double blind, placebo controlled study of the MVA MERS S_DF-1 candidate delivered by i.m. injection. To evaluate the MERS-S-specific antibody responses and safety profile induced by the two dosage levels of MVA-MERS-S_DF-1 the data will be compared to a placebo control group.

Detailed Description
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This will be a Phase Ib, two-center study in approximately 160 healthy adults aged 18-55 years The study is separated in two parts: Part A: The study starts with a single center open-label run-in phase of two dose levels (cohort 1 low dose: 2x10^7 PFU, cohort 2 high dose: 2x10^8 PFU) in 10 healthy subjects. 5 subjects will be allocated to each dose cohort and will receive immunization on day 0 and day 28. Part B: Two-center, randomized, double-blind, placebo-controlled, dose-finding study. This part is a double-blinded trial in approximately 150 healthy subjects. Subjects will be allocated to two different dose cohorts and a placebo cohort; each receiving three vaccine injections.

Official Title
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A Two-center, Randomized, Double-blind, Placebo-controlled, Phase Ib Study to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S_DF-1 in Healthy Study Subjects

Conditions
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MERS (Middle East Respiratory Syndrome)

Intervention / Treatment
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* Biological: MVA-MERS-S_DF1 - Low Dose
* Biological: MVA-MERS-S_DF1 - High Dose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent form. Healthy male and female subjects aged 18-55 years. No clinically significant acute health problems as determined from medical history and physical examination at screening visit. Body mass index 18.5 - 30.0 kg/m2 and weight > 50 kg at screening. Non-pregnant, non-lactating female with negative pregnancy test. Males and females who agree to comply with the applicable contraceptive requirements of the protocol. Exclusion Criteria: Receipt of any vaccine from 2 weeks prior to each trial vac-cination (4 weeks for live vaccines) to 3 weeks after each trial vaccination. Receipt of vaccination against MERS or MVA immunizations.in the medical history. Known allergy to the components of the MVA-MERS-S_DF-1 vaccine product. Evidence in the subject's medical history or in the medical examination that might influence either the safety of the subject or the absorption, distribution, metabolism or excretion of the investigational product. Any confirmed or suspected immunosuppressive or immuno-deficient condition, cytotoxic therapy in the previous 5 years, and/or diabetes. Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blinded with an open-label run-in Phase (Part A) Part A: Open-label Part B: Double-blind
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>Vaccination with 2x10^7 PFU MVA-MERS-S_DF1. Vaccinations will be administered at days 0, 28 or 56, and 336. | Biological: MVA-MERS-S_DF1 - Low Dose<br>* Administrations of the low dose via the intramuscular route<br>|
| Experimental: High Dose<br>Vaccination with 2x10^8 PFU MVA-MERS-S_DF1. Vaccinations will be administered at days 0, 28 or 56, and 336. | Biological: MVA-MERS-S_DF1 - High Dose<br>* Administrations of the high dose via the intramuscular route<br>|
| Placebo Comparator: Placebo<br>Injection with placebo. Injections will be administered at days 0, 28 or 56, and 336. | Other: Placebo<br>* Administrations of placebo via the intramuscular route<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events associated with MVA-MERS-S_DF-1. | Safety and reactogenicity will be assesssed by observation, questionaire and diary. Changes from baseline for safety laboratory measures will be monitored. Occurence of SAE will be collected throughout the entire study duration. | day 1, 14, 29, 42, 56, 84, 168, 336, 364 | 
| Frequency and severity of local injection site reactogenicity signs and symptoms |  | day 1, 14, 29, 42, 84, 336 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Magnitude of MERS-S-specific antibody re-sponses (ELISA and neutralization assays) monitored in a centralized approved laboratory | day 0, 14, 28, 42, 56, 70, 84, 168, 336, 364 (dependent on vaccination scheme) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MERS-CoV, CEPI, viral vector vaccine