Safety, Tolerability and Immunogenicity of Vaccine Candidate MVA-MERS-S

NCT03615911 | Completed Phase 1 Results DMC

• 1 other identifier: UKE-DZIF1-MVA-MERS-S
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially fatal disease with a reported lethality of up to 40% that is under tight epidemiologic control by the World Health Organization (WHO) and currently without registered prevention or treatment option. 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-MERS-S. A subgroup will additionally receive a late booster vaccination. The aim of the study is to assess the safety and tolerability of the candidate vaccine and to characterize its immunogenicity.

Conditions

MERS (Middle East Respiratory Syndrome)

Keywords

vaccine; clinical phase 1; modified vaccinia Ankara vector; MERS-CoV

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Experiencing Solicited Local or Systemic Reactogenicity as Defined by the Study Protocol

  The solicited local adverse events for this study include: Swelling, erythema, induration, hematoma and pain at site of injection The solicited systemic adverse events for this study include: * Fever * Chills * Myalgia (described to the subject as generalized muscle aches) * Arthralgia (described to the subject as generalized joint aches) * Fatigue/Malaise * Headache * Gastrointestinal symptoms The reactogenicity (adverse events) will be assessed via a trained physician taking into account a patient diary. The severity of the adverse event will be measured as specified in the study protocol (grade 0=none, grade 1=mild, grade 2=moderate, grade 3=severe). The adverse event will furthermore be categorized in related vs. not related.

  14 days after each vaccination

• Percentage of Participants Who Experienced an Unsolicited Adverse Event

  The unsolicited adverse events will be assessed via a trained physician taking into account a patient diary. The severity of the adverse event will be measured as specified in the study protocol (grade 0=none, grade 1=mild, grade 2=moderate, grade 3=severe). The adverse event will furthermore be categorized in related vs. not related.

  28 days after each vaccination

• Change of Mean C-reactive Protein (CRP) Levels (Measured in [mg/l]) From Baseline (Day -1 ) as Compared to the End of the Study (D180)

  The safety laboratory measures include: \- Clinical Chemistry: CRP in miligrams per liter \[mg/l\]

  Throughout the study up to conclusion

• Change of Mean White Blood Cell (WBC) Counts (Measured in [Billion Cells/L]) From Baseline (Day -1) as Compared to the End of the Study (D180)

  The safety laboratory measures include Hematology: WBC count in billions per liter \[billion cells/L\]

  Throughout the study up to conclusion

• Percentage of Participants Experiencing a Serious Adverse Event up to Day 180 (Study Completion)

  Serious adverse events are defined as any untoward medical occurrence (whether considered to be related to investigational medicinal product or not) that at any dose: * results in death * is life-threatening * requires inpatient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital abnormality/birth defect * is an Important Medical Event, i.e., an event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Throughout the study up to conclusion

Secondary Outcomes (1)

• Immunogenicity: Number of Participants Who Seroconverted Throughout the Study (up to Study Completion at Day 180)

  Throughout the study up to conclusion

Study Arms (2)

Vaccination with 10^7 PFU MVA-MERS-S

EXPERIMENTAL

Vaccinations occur on days 0 and 28 A subgroup will additionally receive a late booster immunization with 10\^8 PFU MVA-MERS-S 12 months (+/- 4 months) after prime immunization.

Biological: vaccine candidate MVA-MERS-S

Vaccination with 10^8 PFU MVA-MERS-S

EXPERIMENTAL

Vaccinations occur on days 0 and 28 A subgroup will additionally receive a late booster immunization with 10\^8 PFU MVA-MERS-S 12 months (+/- 4 months) after prime immunization.

Biological: vaccine candidate MVA-MERS-S

Interventions

vaccine candidate MVA-MERS-S BIOLOGICAL

vaccination with MVA-MERS-S in two escalating dose regimes

Vaccination with 10^7 PFU MVA-MERS-S; Vaccination with 10^8 PFU MVA-MERS-S

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to understand the subject information and to personally sign and date the informed consent to participate in the study, before completing any study related procedures.
• Provided written informed consent.
• No clinically significant health problems as determined during medical history and physical examination at screening visit.
• Body weight in defined relation to height. Body mass index 18.5 - 30.0 kg/m2 and weight \>50 kg at screening.
• Females of child-bearing potential who agree to apply effective contraception methods (defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly ) from at least 7 days prior to vaccination until the end of the study or females who are permanently sterilized (at least 6 weeks post-sterilization).
• Males who agree to apply effective contraception methods from day 0 through day 56.
• Be willing to refrain from blood donation during the course of the study.
• The subject is co-operative and available for the entire study.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria are met at screening or at day -1:
• Prior receipt of a MERS vaccine or MVA immunizations.
• Receipt of any vaccine in the 2 weeks prior to 1st trial vaccination (4 weeks for live vaccines) or planned receipt of any vaccine in the 3 weeks following the 2nd trial vaccination.
• Known allergy to the components of the MVA-MERS-S vaccine product as eggs, chicken proteins, and gentamycin or history of life-threatening reactions to vaccine containing the same substances.
• Participation in a clinical trial or use of an investigational product within 30 days or five times the half-life of the investigational drug -whichever is longer- prior to receiving the first dose within this study.
• 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 under investigation.
• Any positive result for human immunodeficiency virus (HIV)1/2 antibody, hepatitis C virus (HCV) antibody or hepatitis B surface antigen (HBsAg) testing.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years, and/or diabetes.
• Participants with inflammatory, infectious and neuroinflammatory underlying disease which could cause an expected impairment of the blood brain barrier such as meningitis, multiple sclerosis, epilepsy, or Alzheimer's disease.
• Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, excluding a single febrile seizure as a child.
• Known history of Guillain-Barré Syndrome.
• Active malignancy or history of metastatic or hematologic malignancy.
• Suspected or known alcohol and/or illicit drug abuse within the past 5 years.
• Moderate or severe illness and/or fever \>38°C within 1 week prior to vaccination.
• Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period.

Sponsors & Collaborators

• Marylyn Addo: lead
• Philipps University Marburg: collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• Charite University, Berlin, Germany: collaborator
• Bernhard Nocht Institute for Tropical Medicine: collaborator
• University of Cologne: collaborator

Study Sites (1)

CTC North GmbH & Co. KG at the University Medical Center Hamburg-Eppendorf

Hamburg, 20251, Germany

Location

Related Publications (10)

• Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012 Nov 8;367(19):1814-20. doi: 10.1056/NEJMoa1211721. Epub 2012 Oct 17.

  PMID: 23075143 BACKGROUND

• Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013 Jun 27;368(26):2487-94. doi: 10.1056/NEJMoa1303729. Epub 2013 May 29.

  PMID: 23718156 BACKGROUND

• van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, Osterhaus AD, Haagmans BL, Gorbalenya AE, Snijder EJ, Fouchier RA. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio. 2012 Nov 20;3(6):e00473-12. doi: 10.1128/mBio.00473-12.

  PMID: 23170002 BACKGROUND

• Agnihothram S, Gopal R, Yount BL Jr, Donaldson EF, Menachery VD, Graham RL, Scobey TD, Gralinski LE, Denison MR, Zambon M, Baric RS. Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses. J Infect Dis. 2014 Apr 1;209(7):995-1006. doi: 10.1093/infdis/jit609. Epub 2013 Nov 18.

  PMID: 24253287 BACKGROUND

• Song F, Fux R, Provacia LB, Volz A, Eickmann M, Becker S, Osterhaus AD, Haagmans BL, Sutter G. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol. 2013 Nov;87(21):11950-4. doi: 10.1128/JVI.01672-13. Epub 2013 Aug 28.

  PMID: 23986586 BACKGROUND

• Sutter G, Moss B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10847-51. doi: 10.1073/pnas.89.22.10847.

  PMID: 1438287 BACKGROUND

• Haagmans BL, van den Brand JM, Raj VS, Volz A, Wohlsein P, Smits SL, Schipper D, Bestebroer TM, Okba N, Fux R, Bensaid A, Solanes Foz D, Kuiken T, Baumgartner W, Segales J, Sutter G, Osterhaus AD. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science. 2016 Jan 1;351(6268):77-81. doi: 10.1126/science.aad1283. Epub 2015 Dec 17.

  PMID: 26678878 BACKGROUND

• Weskamm LM, Fathi A, Raadsen MP, Mykytyn AZ, Koch T, Spohn M, Friedrich M; MVA-MERS-S Study Group; Haagmans BL, Becker S, Sutter G, Dahlke C, Addo MM. Persistence of MERS-CoV-spike-specific B cells and antibodies after late third immunization with the MVA-MERS-S vaccine. Cell Rep Med. 2022 Jul 19;3(7):100685. doi: 10.1016/j.xcrm.2022.100685.

  PMID: 35858586 DERIVED

• Fathi A, Dahlke C, Krahling V, Kupke A, Okba NMA, Raadsen MP, Heidepriem J, Muller MA, Paris G, Lassen S, Kluver M, Volz A, Koch T, Ly ML, Friedrich M, Fux R, Tscherne A, Kalodimou G, Schmiedel S, Corman VM, Hesterkamp T, Drosten C, Loeffler FF, Haagmans BL, Sutter G, Becker S, Addo MM. Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome. Nat Commun. 2022 Jul 19;13(1):4182. doi: 10.1038/s41467-022-31557-0.

  PMID: 35853863 DERIVED

• Koch T, Dahlke C, Fathi A, Kupke A, Krahling V, Okba NMA, Halwe S, Rohde C, Eickmann M, Volz A, Hesterkamp T, Jambrecina A, Borregaard S, Ly ML, Zinser ME, Bartels E, Poetsch JSH, Neumann R, Fux R, Schmiedel S, Lohse AW, Haagmans BL, Sutter G, Becker S, Addo MM. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. Lancet Infect Dis. 2020 Jul;20(7):827-838. doi: 10.1016/S1473-3099(20)30248-6. Epub 2020 Apr 21.

  PMID: 32325037 DERIVED

Related Links

• Middle East respiratory syndrome coronavirus situation updates

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Prof. Marylyn M. Addo
• Organization: University Medical Center Hamburg-Eppendorf

m.addo@uke.de

+49 40 7410

Study Officials

• Marylyn M Addo, Prof. Dr.

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Marylyn M. Addo, Principal Investigator, Head of the Department of Infectious Diseases

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: August 6, 2018
• Study Start: November 28, 2017
• Primary Completion: April 15, 2019
• Study Completion: May 10, 2019
• Last Updated: October 6, 2020
• Results First Posted: October 6, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)