Safety, Reactogenicity and Immunogenicity of a Novel MVA-SARS-2-ST Vaccine Candidate

Study Overview
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Brief Summary
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This will be a phase I, single-center trial, including a total of 30 participants in two cohorts. Cohort 1 (n=6): Healthy male or female adults aged 18 - ≤ 60 previously primary immunized with two vaccinations with any regimen using any EU marketed SARS-CoV-2 vaccine (mRNA-, vector-, protein-based, attenuated SARS-CoV-2 virus) or with a single application of COVID-19 Vaccine Janssen. Cohort 2 (n=24): Healthy male or female adults aged 18 - ≤ 60 primary immunized with two vaccinations with any regimen using any EU marketed SARS-CoV-2 vaccine (mRNA-, vector-, protein-based, attenuated SARS-CoV-2 virus) or with a single application of COVID-19 Vaccine Janssen and subsequently booster immunized with any EU marketed mRNA vaccine Both cohorts will be assigned to inhaled vaccination with MVA-SARS-2-ST

Official Title
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Safety, Reactogenicity and Immunogenicity of a Novel MVA-SARS-2-ST Vaccine Candidate Administered as Inhalation Boost in SARS-CoV-2 Immunized Adults - Phase I Study

Conditions
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COVID-19 Vaccines

Intervention / Treatment
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* Biological: MVA-SARS-2-ST


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must not be enrolled before all inclusion criteria (including test results) are confirmed. Subjects meeting all of the criteria listed below will be included in the study. Signed written informed consent from subject prior to any study-related procedure and willingness to comply with treatment and follow-up procedures Healthy men or women, aged ≥ 18 ≤ 60 at day of inclusion having received either primary immunization (cohort 1) with any regimen using any EU marketed SARS- CoV-2 vaccine or subsequently booster immunization (cohort 2) with any EU marketed mRNA vaccine at least 3 months prior to enrollment Adults with SARS-CoV-2 specific IgG concentration between 10 RU/ml and 1200 RU/ml determined by Anti-SARS-CoV-2-QuantiVac-ELISA (IgG) Males or non-pregnant, non-lactating females of child-bearing potential with negative pregnancy test at screening who agree to comply with the applicable contraceptive requirements of the protocol (Section 3.4) from at least 14 days prior to vaccination and during the entire duration of the study. or Females without child-bearing potential defined as follows: at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy or hysterectomy or uterine agenesis or ≥ 50 years and in postmenopausal state > 1 year or < 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening Normal pulmonary function: FEV1 predicted ≥ 80% and FEV1/FVC > 70% Body mass index 18.5 - 30.0 kg/m2 and weight > 50 kg at screening Subject is capable of understanding the investigational nature, potential risks and benefits of the clinical trial Exclusion Criteria: Subjects are excluded from the study if any of the following criteria are met at screening or on dosing day. Previous MVA or rMVA vaccination Known allergy to the components of the SARS-CoV-2 vaccine product as chicken proteins or history of life-threatening reactions to vaccine containing the same substances Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine Any laboratory value outside the reference range that the investigator considers to be of clinical relevance; safety laboratory screening evaluation can be repeated a maximum of two times Any finding in the medical history and physical examination deviating from normal and assessed as clinically relevant by the investigator Evidence in the subject's medical history or in the medical examination that might influence the absorption, distribution, metabolism or excretion of the investigational medicinal product Current smoking/ vaping or smoking /vaping in the previous year. Clinically relevant findings in ECG Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years, and/or diabetes Asthma, chronic obstructive pulmonary disease or other lung disease Respiratory tract infection in the 4 weeks prior to study treatment Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding a single febrile seizure as a child Known intolerance to medication used during bronchoscopy, i.e. midazolam and lidocaine. Treatment with ß-adrenoceptor antagonists Alcohol abuse (consumption of more than 20 g per day for females and 30 g per day for males) Drug abuse or positive drug screening Any positive result for HIV1/2, HCV antibody or HBs antigen testing Moderate or severe illness and/or fever >38 °C within 1 week prior to vaccination History of blood donation within 60 days of enrollment or plans to donate within the treatment phase Participation in a clinical trial or use of an investigational product within 30 days or five times the half-life of the investigational product -whichever is longer- prior to receiving the first dose within this study Investigator or employee of the study site or Sponsor with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, natural or adopted child) of the investigator or employee with direct involvement in the proposed study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 x 107 IU/dose MVA-SARS-2-ST<br>All Participants will receive a single booster dose of 1 x 107 IU MVA-SARS-2-ST in 0.5 mL as inhalation (total inhaled volume 0.5 mL) | Biological: MVA-SARS-2-ST<br>* In this trial MVA-SARS-2-ST will be used. Each vial contains 1 x 107 IU/dose MVA-SARS-2-ST in 0.5 mL as active ingredient. The solution will be used for nebulization and direct administration to the respiratory tract.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 0 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 1 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 2 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 3 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 4 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 5 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 6 | 
| The nature, frequency and severity of adverse events associated with MVA-SARS-2-ST | Occurrence of solicited local reactogenicity signs and symptoms | day 7 | 
| Change from baseline of pulmonary function associated with MVA-SARS-2-ST | Change from baseline of pulmonary function measured by spirometry as forced vital capacity (FVC) (%) | day 0 (2h), day 1, 3, 7, 14, 28, 56, 140 | 
| Change from baseline of pulmonary function associated with MVA-SARS-2-ST | Change from baseline of pulmonary function measured by spirometry as forced expiratory volume in 1 second (FEV1) (%) | day 0 (2h), day 1, 3, 7, 14, 28, 56, 140 | 
| Change from baseline of pulmonary function associated with MVA-SARS-2-ST | Change from baseline of pulmonary function measured by spirometry as FEV1/FVC (%) | day 0 (2h), day 1, 3, 7, 14, 28, 56, 140 | 
| Change from baseline of pulmonary function associated with MVA-SARS-2-ST | Change from baseline of pulmonary function measured by peak flow as peak expiratory flow (PEF) frequently | day 0 and twice daily on days 1, 2, 3, 4, 5, 6, 7 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 0 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 1 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 2 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 3 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 4 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 5 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 6 | 
| Occurrence of solicited systemic reactogenicity signs and symptoms associated with MVA-SARS-2-ST | Occurrence of solicited systemic reactogenicity signs and symptoms vaccination | day 7 | 
| Occurrence of unsolicited adverse events (AE) associated with MVA-SARS-2-ST | Occurrence of unsolicited adverse events (AE) | from day 0 to day 28 after vaccination | 
| Change of safety laboratory measures associated with MVA-SARS-2-S | Change from baseline of safety laboratory measures | day 1, 3, 7, 14, 28, 56, 140 | 
| Occurrence of serious adverse events (SAE) associated with MVA-SARS-2-ST | Occurrence of serious adverse events (SAE) | through study completion, an average of 5 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate immunogenicity of the candidate MVA-SARS-2-ST | Change from baseline of levels of binding antibodies against SARS-CoV-2 spike S1 protein measured by ELISA in blood | day 7, 14, 28, 56 and 140 | 
| To evaluate immunogenicity of the candidate MVA-SARS-2-ST | Change from baseline of levels of binding antibodies against SARS-CoV-2 spike S1 protein measured by ELISA in (bronchial alveolar lavage) BAL on day 14 | day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MVA-SARS-COV-2, MVA-SARS-2-ST