Safety and Immunogenicity of the Candidate Vaccine MVA-SARS-2-S and a Booster Vaccination With a Licensed Vaccine Against COVID-19

• ClinicalTrials.gov Identifier: NCT04569383
• Recruitment Status: Completed
• First Posted: September 29, 2020
• Last Update Posted: November 5, 2021
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

Tracking Information

• First Submitted Date: September 21, 2020
• First Posted Date: September 29, 2020
• Last Update Posted Date: November 5, 2021
• Actual Study Start Date: October 5, 2020
• Actual Primary Completion Date: August 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 28, 2020)

Percentage of Participants Experiencing Solicited Local or Systemic Reactogenicity as Defined by the Study Protocol [ Time Frame: during the entire study (up to 6 months) ]

Safety and reactogenicity will be assessed by observation, questionaire and diary. Occurence of Serious Adverse Events (SAE) will be collected throughout the entire study duration.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 28, 2020)

Immunogenicity. Number of participants who seroconverted [ Time Frame: during the entire study (up to 6 months) ]

Magnitude of SARS-CoV2-specific antibody responses (ELISA and neutralization assays) monitored in an approved laboratory

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of the Candidate Vaccine MVA-SARS-2-S and a Booster Vaccination With a Licensed Vaccine Against COVID-19
• Official Title: An Open, Single-center Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-SARS-2-S and Heterologous Booster Vaccinations With a Licensed Vaccine Against COVID-19

Brief Summary

In this phase I first-in-human clinical trial, healthy volunteers in two different dose cohorts will be vaccinated twice with the candidate vaccine MVA-SARS-2-S. A subgroup will receive a heterologous booster vaccination with a licensed COVID-19 vaccine.

The aim of the study is to assess the safety and tolerability of the candidate vaccine and to characterize its immunogenicity.

Detailed Description

The vaccine contains a Modified Vaccinia Virus Ankara (MVA) vector expressing the SARS-CoV-2 spike protein (S). A total of 30 participants will receive the following vaccine regime:

15 participants will receive 10^7 infectious units (IU) of MVA-SARS-2-S on days 0 and 28.

15 participants will receive 10^8 IU of MVA-SARS-2-S on days 0 and 28. Safety and immunogenicity data will be collected throughout the study, which concludes at day 168.

A subgroup will receive a heterologous booster vaccination with a licensed COVID-19 vaccine. Vaccinees will receive two doses of the Comirnaty vaccine (21 days interval).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Covid19

Intervention

• Biological: MVA-SARS-2-S vaccinations (days 0 & 28)
  Vaccination with MVA-SARS-2-S in two escalating dose regimens
• Biological: Comirnaty
  Vaccination with Comirnaty (21 day interval)

Study Arms

• Experimental: 1x10E7 IU (low dose)
  1x10E7 IU MVA-SARS-2-S. Subgroup will receive additionally Comirnaty
  Interventions:

  • Biological: MVA-SARS-2-S vaccinations (days 0 & 28)
  • Biological: Comirnaty
• Experimental: 1x10E8 IU (high dose)
  1x10E8 MVA-SARS-2-S. Subgroup will receive additionally Comirnaty
  Interventions:

  • Biological: MVA-SARS-2-S vaccinations (days 0 & 28)
  • Biological: Comirnaty

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 28, 2020): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 24, 2021
• Actual Primary Completion Date: August 24, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Written informed consent
• Healthy male and female adults aged 18-55 years
• No clinically significant health problems as determined during medical history and physical examination at screening visit
• Body mass index 18.5 - 30.0 kg/m2 and weight > 50 kg at screening
• Adults male or non-pregnant, non-lactating female with negative pregnancy test
• Males and females who agree to comply with the applicable contraceptive requirements of the protocol

Inclusion criteria for the subjects before the 3rd/4th (=booster) vaccination:

1. Ability to understand the subject information and to personally name, sign and date the in-formed consent to participate in the study.
2. Provided written informed consent.
3. Continues to be in stable health condition as determined during medical history and physi-cal examination on vaccination visits.
4. Non-pregnant, non-lactating female with a negative pregnancy test at screening and on dosing days (prior to vaccination).
5. Be willing to refrain from blood donation during the course of the study.
6. The subject is co-operative and available for the entire study.
7. Need to have participated in previous part of the MVA-SARS-2-S vaccine study (Eudra-CT No: 2020-002998-10)

Exclusion Criteria:

• Prior exposure to SARS-CoV-2
• Receipt of any vaccine from 4 weeks prior to each trial vaccination (8 weeks for live vaccines) to 6 weeks after each trial vaccination
• Previous rMVA immunization
• Known allergy to the components of the SARS-CoV-2 vaccine product
• Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine
• 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
• Clinically relevant findings in ECG
• Any confirmed or suspected immunosuppressive or immunodeficient 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

Exclusion criteria for the subjects before the 3rd/4th (=booster) vaccination:

1. Prior infection with SARS-CoV-2 in medical history (documented by PCR test)
2. Receipt of any vaccine from 2 weeks prior to each trial vaccination (4 weeks for live vac-cines) to 2 weeks after each trial vaccination.
3. Receipt any COVID-19 vaccine (investigational or licensed other than MVA-SARS-2-S be-fore vaccination throughout end of study).
4. Known allergy to the components of t Comirnaty®.
5. Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the trial vaccine.
6. Participation in a clinical trial other than the MVA-SARS-2-S vaccine trial or use of an in-vestigational product other than MVA-SARS-2-S 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.
7. Evidence in the subject's medical history or in the medical examination that might influence

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04569383
• Other Study ID Numbers: UKE-DZIF-SARS-CoV-2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• Original Responsible Party: Same as current
• Current Study Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Original Study Sponsor: Same as current

Collaborators

• German Center for Infection Research
• Philipps University Marburg Medical Center
• Ludwig-Maximilians - University of Munich

Investigators

• Principal Investigator: Marylyn M Addo, MD; Universitätsklinikum Hamburg-Eppendorf

• PRS Account: Universitätsklinikum Hamburg-Eppendorf
• Verification Date: November 2021