MVA-BN-RSV Vaccine Trial

A Randomized, Double-blind, Phase 3 Trial to Assess Clinical Efficacy, Safety and Reactogenicity of the Recombinant MVA-BN® -RSV Vaccine in Adults ≥60 Years of Age

Phase 3 randomized, double blind study comparing recombinant MVA-BN-RSV vaccine vs placebo for efficacy and safety in adults >=60 years of age

Study Overview

• Status: Terminated
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Biological: MVA-BN-RSV vaccine; Biological: Tris Buffered Saline (TBS)

• Study Type: Interventional
• Enrollment (Actual): 20419
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin GbR
  • Berlin, Germany, 13187
    • Studienzentrum Diabetespraxis Dr. Braun
  • Cottbus, Germany, 03050
    • MECS Cottbus GmbH
  • Dresden, Germany, 01069
    • Klinsche Forschung Dresden GmbH
  • Frankfurt, Germany, 60596
    • IKF Institut fuer klinische Forschung Frankfurt
  • Hannover, Germany, 30159
    • Klinische Forschung Hannover-Mitte GmbH
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover (MHH)
  • Hanover, Germany, 30449
    • Siteworks GmbH
  • Heidelberg, Germany, 69115
    • Siteworks Zentrum für Klinische Studien Heidelberg
  • Leipzig, Germany, 04103
    • SIBAmed Studienzentrum GmbH & Co. KG
  • Mainz, Germany, 55128
    • Dermatologische Gemeinschaftspraxis Dres. Quist
  • Oldenburg, Germany, 23758
    • RED Institut GmbH
  • Rendsburg, Germany, 24768
    • Siteworks Prufzentrum Rendsburg - HNO Research GmbH
  • Schwerin, Germany, 19055
    • Klinische forschung Schwerin GmbH
  • Wiesbaden, Germany, 65189
    • Intermed GmbH, Institut fuer medizinische Forschung und Arzneimittelsicherheit
• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center, LLC
    • Birmingham, Alabama, United States, 35209
      • Central Alabama Research
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC d/b/a Accel Research Sites
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliation Research Center
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Lenzmeier Family Medicine / CCT Research
    • Mesa, Arizona, United States, 85210
      • Aventiv Research Inc.
    • Phoenix, Arizona, United States, 85014
      • Phoenix Clinical LLC
    • Phoenix, Arizona, United States, 85044
      • Cognitive Clinical Trials, LLC
    • Phoenix, Arizona, United States, 85018
      • Pain Center of Arizona
    • Tempe, Arizona, United States, 85284
      • Hope Research Institute
    • Tempe, Arizona, United States, 85283
      • Fiel Family and Sports Medicine/CCT Research
    • Tucson, Arizona, United States, 85710
      • Tucson Neuroscience Research, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Lynn Institute of the Ozarks
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, LLC
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research 002, LLC
    • Huntington Park, California, United States, 90255
      • Join Clinical Trials
    • La Mesa, California, United States, 91942
      • Paradigm Clinical Research Center
    • La Palma, California, United States, 90623
      • Atella Clinical Research LLC
    • Lancaster, California, United States, 93534
      • Chemidox Clinical Trials Inc.
    • Long Beach, California, United States, 90806
      • Ark Clinical Research
    • Los Angeles, California, United States, 90057
      • Matrix Clinical Research
    • San Diego, California, United States, 92123
      • California Research Foundation
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Lynn Institute of Denver
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Hialeah, Florida, United States, 33016
      • Doral Medical Research
    • Maitland, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Miami, Florida, United States, 33125
      • Optimus U Corporation
    • Miami, Florida, United States, 33184
      • De La Cruz Research Center, LLC
    • Miami Lakes, Florida, United States, 33016
      • Global Health Research Center, Inc
    • Pembroke Pines, Florida, United States, 33024
      • Pines Care Research Center, LLC
    • Pembroke Pines, Florida, United States, 33026
      • Ideal Clinical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Centricity Research Columbus Multispecialty
    • Decatur, Georgia, United States, 30030
      • Accel Research Site - Neurostudies
    • Lilburn, Georgia, United States, 30047
      • Lifeline Primary Care/CCT Research
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Bingham Memorial Hospital
    • Idaho Falls, Idaho, United States, 83404
      • Clinical Research Prime
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60625
      • Great Lakes Clinical Trials at Ravenswood Rheumatology
    • Oak Lawn, Illinois, United States, 60453
      • Accelacare- DuPage Medical Group
  • Indiana
    • Evansville, Indiana, United States, 47714
      • AES Evansville
  • Iowa
    • Ames, Iowa, United States, 50010
      • Accellacare and McFarland Clinic
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Med Pharmics, LLC
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group
    • Rockville, Maryland, United States, 20854
      • Meridian Clinical Research
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices and Research, LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • The Clinical Research Center, LLC
    • Saint Louis, Missouri, United States, 63104
      • Edward A. Doisy Research Center-Saint Louis University Center for Vaccine Development
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research, LLC
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research Associates, LLC
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research Inc
    • Omaha, Nebraska, United States, 68144
      • Midwest Regional Health Services, LLC/CCT Research
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Synexus Clinical Research US, Inc.
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89119
      • Santa Rosa Medical Centers of Nevada/ CCT Research
  • New Jersey
    • Raritan, New Jersey, United States, 08869
      • Amici Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • MedPharmics, LLC
  • New York
    • Cortland, New York, United States, 13045
      • Certified Research Associates
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research LLC
    • New York, New York, United States, 10455
      • CHEAR Center LLC
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research Inc.
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Accellacare - Raleigh Medical Group
    • Charlotte, North Carolina, United States, 28209
      • Accellacare Research of Charlotte
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Raleigh, North Carolina, United States, 27609
      • Accellacare - Raleigh Medical Group
    • Rocky Mount, North Carolina, United States, 27804
      • Accellacare, Inc. - Rocky Mount
    • Statesville, North Carolina, United States, 28625
      • Accellacare - Piedmont
    • Wilmington, North Carolina, United States, 28401
      • Accellacare of Wilmington
    • Winston-Salem, North Carolina, United States, 27103
      • Progressive Medicine of the Triad, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research
  • Oklahoma
    • Moore, Oklahoma, United States, 73160
      • Tekton Research
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73111
      • Lynn Health Science Institute East
    • Yukon, Oklahoma, United States, 73099
      • Tekton Research Inc.
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Capital Area Research, LLC
    • Philadelphia, Pennsylvania, United States, 19107
      • DM Clinical Research
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research- Providence
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research US, Inc.
    • Anderson, South Carolina, United States, 29621
      • Velocity Clinical Research Anderson
    • Little River, South Carolina, United States, 29566
      • Main Street Physician's Care-Waterway
  • Tennessee
    • Knoxville, Tennessee, United States, 37938
      • Accellacare of Knoxville
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc.
    • Edinburg, Texas, United States, 78539
      • Invesclinic US LLC
    • Houston, Texas, United States, 77065
      • DM Clinical Research
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research
    • Plano, Texas, United States, 75093
      • Research Your Health
    • Round Rock, Texas, United States, 78681
      • Be Well Clinical Studies
    • Sugar Land, Texas, United States, 77479
      • Mt Olympus Medical Research LLC
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Holladay, Utah, United States, 84117
      • Olympus Family Medicine/CCT Research
    • Layton, Utah, United States, 84041
      • Tanner Clinic
    • Ogden, Utah, United States, 84405
      • South Ogden Family Medicine/ CCT Research
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • Virginia
    • Annandale, Virginia, United States, 22003-7347
      • Clinical Alliance for Research and Education Infectious Disease
    • Portsmouth, Virginia, United States, 23703
      • Meridian Clinical Research, LLC
    • Suffolk, Virginia, United States, 23435
      • Centricity Research Suffolk Primary Care
  • Washington
    • Port Orchard, Washington, United States, 98366
      • Sound Medical Research
    • Spokane, Washington, United States, 99204
      • MultiCare Health System-DMOB (Deaconess Medical Office Building)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female subjects ≥60 years of age.
2. Informed Consent signed by the subject.
3. Subjects may have one or more chronic medical conditions e.g., mild to moderate underlying illnesses such as chronic cardiac diseases and chronic lung disease (asthma and chronic obstructive pulmonary disease [COPD]), congestive heart failure (CHF), hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, that is clinically stable as assessed by the investigator.
4. Absence of known, current, and life-limiting diagnoses that render survival to completion of the protocol unlikely.
5. Ability to comply with trial requirements, which necessitates access to transportation to on-site visits, including symptom visits for a nasopharyngeal swab.
6. Willingness and ability to utilize an application on a personal device (i.e., smartphone, tablet, etc.) or a provisioned device to record solicited events and record all per protocol required data during the surveillance period.
7. For women of childbearing potential (WOCBP), agreement to use an acceptable method of contraception during the trial and a negative urine pregnancy test within 24 hours prior to vaccination.

Exclusion Criteria:

1. History of or current clinical manifestation of any serious medical condition that in the opinion of the investigator would compromise the safety of the subject, confound data interpretation, or would limit the subject's ability to complete the trial.
2. History of or active autoimmune disease, including diabetes mellitus type I. Vitiligo or hypothyroidism requiring thyroid replacement therapy are not exclusions. Rheumatoid arthritis not requiring immunomodulatory and/or immunosuppressant treatment is not an exclusion.
3. Known or suspected impairment of immunologic functions, including chronic inflammatory bowel disorders.
4. Clinically significant mental disorder that would prevent patients from giving informed consent and complying with study procedures (e.g., completion of the electronic diary).
5. Active or recent (within 6 months before enrollment) history of chronic alcohol abuse.
6. History of a serious reaction to any prior vaccination or Guillain-Barré syndrome (GBS) within 6 weeks of any prior influenza immunization.

7. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g., tris(hydroxymethyl)-amino methane, chicken embryo fibroblast proteins, gentamycin, ciprofloxacin; this includes:

   • Known allergy to eggs or aminoglycosides
   • History of anaphylaxis or severe allergic reaction to any vaccine

8. Any administration or planned administration of:

   • A licensed live or vector-based vaccine within 30 days prior to or after trial vaccine administration.
   • A licensed inactivated or ribonucleic acid (RNA)-based vaccine within 14 days prior to or after trial vaccine administration.
9. Previous vaccination with an RSV vaccine, or any planned vaccination with an RSV vaccine other than the trial vaccine.
10. Planned chronic, systemic administration (defined as more than 14 days) of >10 mg prednisone (or equivalent)/day or any other systemic use of immunemodifying drugs during a period starting from 3 months prior to first administration of the trial vaccine and ending at the End of Study Visit (EOS). The use of topical, inhaled, ophthalmic and nasal glucocorticoids is permitted.
11. Administration or planned administration of immunoglobulins and/or any blood products during a period starting from 3 months prior to first administration of the trial vaccine and during the trial.
12. Known uncontrolled coagulation disorder. Anticoagulant treatment under adequate control for cardiovascular prophylaxis or prophylaxis of thromboembolic disease or stroke in the setting of atrial fibrillation are permitted.
13. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days prior to the administration of the trial vaccine, or planned administration of such a drug or vaccine between enrollment in the trial and until the end of the clinical trial including follow-up. [For US Only]
14. Involvement with this trial as research personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Single dose MVA-BN-RSV; Single dose (Week 0): MVA-BN-RSV virus with a titer of at least 3x10E8 Inf.U/0.5mL (intramuscular vaccination)	Biological: MVA-BN-RSV vaccine; One injection, suspension for injection, intramuscular use, 0.5mL MVA-BN-RSV virus with a titer of at least 3 x 10E8 infectious units (Inf.U)/0.5mL in a Tris buffer at pH 7.7.
Experimental: Group 2: Single dose Placebo; Single dose of TBS (intramuscular injection; 0.5mL)	Biological: Tris Buffered Saline (TBS); One injection, solution for injection, intramuscular use, 0.5mL TBS, pH 7.7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of PCR Confirmed RSV-associated LRTD With at Least 3 Symptoms	RSV-associated lower respiratory tract disease (LRTD) is defined by the presence of clinical evidence of at least 1 sign or symptom of acute respiratory disease (ARD) and at least 3 LRTD signs or symptoms with onset ≥14 days following vaccination until the end of one RSV season (up to 12 months after vaccination), confirmed and documented by a medical professional, together with RSV disease confirmed by polymerase chain reaction (PCR)	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Occurrence of PCR Confirmed RSV-associated LRTD With at Least 2 Symptoms	RSV-associated lower respiratory tract disease (LRTD) is defined by the presence of clinical evidence of at least 1 sign or symptom of acute respiratory disease (ARD) and at least 2 LRTD signs or symptoms with onset ≥14 days following vaccination until the end of one RSV season (up to 12 months after vaccination), confirmed and documented by a medical professional, together with RSV disease confirmed by polymerase chain reaction (PCR)	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of PCR Confirmed RSV-associated ARD	RSV-associated acute respiratory disease (ARD) is defined by the presence of either one ARD symptom lasting for at least 24 hours or two simultaneously occurring ARD symptoms (irrespective of duration), with onset ≥14 days following vaccination until the end of one RSV season (up to 12 months after vaccination), confirmed and documented by a medical professional, together with RSV disease confirmed by polymerase chain reaction (PCR)	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Occurrence of Complications Related to PCR-confirmed RSV Disease	RSV-specific complications include the presence of acute clinical consequences of RSV infection, such as pneumonia (incl. bacterial superinfection), sepsis, positive blood culture, and pneumothorax as well as longer term consequences of RSV-specific symptoms, such as persistent worsening of chronic conditions (e.g. COPD), new onset of persistent medical conditions (e.g. chronically impaired lung function, asthma) or a worsening of the functional status of the patient, e.g. new onset of nursing or assisted living need. RSV disease had to be confirmed by PCR testing.	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Occurrence of Hospitalization Due to Confirmed RSV Disease or Due to Any Complication Related to RSV-confirmed Respiratory Disease	Hospitalization due to PCR confirmed RSV disease and/or any complication related to PCR-confirmed RSV disease. RSV-specific complications include the presence of acute clinical consequences of RSV infection, such as pneumonia (incl. bacterial superinfection), sepsis, positive blood culture, and pneumothorax as well as longer term consequences of RSV-specific symptoms, such as persistent worsening of chronic conditions (e.g. COPD), new onset of persistent medical conditions (e.g. chronically impaired lung function, asthma) or a worsening of the functional status of the patient, e.g. new onset of nursing or assisted living need. RSV disease had to be confirmed by PCR testing.	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Occurrence of Severe PCR Confirmed RSV-associated LRTD	Severe RSV-associated LRTD is defined by the presence of clinical evidence of at least 1 sign or symptom of ARD and at least 1 of the following signs or symptoms with onset ≥14 days following vaccination until the end of one RSV season (up to 12 months after vaccination), confirmed and documented by a medical professional, together with RSV disease confirmed by polymerase chain reaction (PCR): 1) hypoxemia (oxygen saturation <92% at rest in conjunction with an at least 3% decrease from baseline); 2) respiratory rate >25 breaths/Min; 3) imaging evidence of new onset of bronchitis, bronchiolitis, or pneumonia	From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Number of Participants With Serious Adverse Events	Number and percentage of study participants reporting any serious adverse events at any time during the trial period.	From vaccination through study termination, up to 16 months
Number of Participants With Grade 3 or Higher Adverse Events	Number and percentage of study participants reporting any grade 3 or higher unsolicited adverse events assessed as related to study vaccine	Within 29 days after vaccination
Number of Participants With Solicited Local Adverse Events	Number and percentage of study participants reporting injection site reactions (solicited via electronic diaries) within 8 days after vaccination. The number of participants analyzed and the percentages are based on the subset of participants in the Safety Set that completed the electronic diary.	Within 8 days after vaccination
Number of Participants With Solicited Systemic Adverse Events	Number and percentage of study participants reporting systemic reactions (solicited via electronic diaries) within 8 days after vaccination. The number of participants analyzed and the percentages are based on the subset of participants in the Safety Set that completed the electronic diary.	Within 8 days after vaccination
Number of Participants With Unsolicited Adverse Events	Number and percentage of study participants reporting any unsolicited adverse events within 29 days after vaccination.	Within 29 days after vaccination
RSV-specific T-cell Responses	RSV-specific T-cell responses measured 1 week post vaccination in a subset of the study population	1 week after vaccination
RSV-specific Serum IgG Antibody Titers	Geometric Mean Titers (GMTs) based on RSV-specific Immunoglobulin G (IgG) Enzyme-linked Immunosorbent Assay (ELISA)	2 weeks after vaccination
RSV-specific Serum Neutralizing Antibody Titers (Subtype A)	Geometric Mean Titers (GMTs) based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype A). Results below the lower limit of quantitation (LLOQ) are included with a value of 1/2 LLOQ	2 weeks after vaccination
RSV-specific Serum Neutralizing Antibody Titers (Subtype B)	Geometric Mean Titers (GMTs) based on RSV-specific Plaque Reduction Neutralization Test (PRNT; against subtype B). Results below the lower limit of quantitation (LLOQ) are included with a value of 1/2 LLOQ	2 weeks after vaccination

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Investigators: Study Director: Bernard Hoet, MD, Bavarian Nordic GmbH

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; Respiratory Syncytial Virus Infections; Anti-Infective Agents; Antiviral Agents; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: RSV-MVA-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No