RSV-MVA-BN Vaccine Phase II Trial in ≥ 55 Year Old Adults
Condition: Respiratory Syncytial Virus Infections
MeSH terms: Respiratory Syncytial Virus Infections
Intervention: MVA-BN-RSV; Placebo
Intervention description: MVA-mBN294B; Tris Buffered Saline, sterile
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 420.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: RSV Vaccines; Respiratory Syncytial Virus Vaccines

Summary:

      A total of 400 subjects will be recruited into five treatment subject groups à 80
      subjects.Subject will receive two administrations 4 weeks apart which will consist of
      MVA-BN-RSV Dose 1, MVA-BN-RSV Dose 2 or Placebo (TBS).

      86 subjects from 2 treatment groups (43 per treatment group) are supposed to receive one
      (booster) dose of MVA-BN-RSV vaccine approximately one year after their first vaccination. In
      this booster substudy, eligible subjects will receive the same dose they received during the
      main trial.
    

Eligibility criteria:

        Inclusion Criteria (Main study):

          1. Male and female subjects, ≥ 55 years of age.

          2. Prior to performance of any trial specific procedures, the subject has read, signed
             and dated an informed consent form, having been advised of the risks and benefits of
             the trial in a language understood by the subject, and has signed the Health Insurance
             Portability and Accountability Act (HIPAA) authorization form.

          3. Subjects without symptomatic cardiopulmonary and/or metabolic disease. Note that
             subjects who have any active symptoms related to cardiac and/or pulmonary and/or
             metabolic disease (including e.g. uncontrolled asthma, angina pectoris, hyperglycaemia
             or other episodic symptoms), or who receive ongoing therapy to control current, active
             symptoms, are not eligible. Subjects on stable treatment (no change in ≥ 1 month) for
             previous and controlled symptoms or conditions are eligible. The following are
             examples of subjects who may bear cardiopulmonary or metabolic diagnoses but who would
             remain eligible:

               -  Subjects on stable (no change in ≥ 1 month) therapy for findings (e.g.
                  hypertension, hyperlipidemia) which are not associated with current symptoms or
                  disability.

               -  Subjects with type II diabetes mellitus are considered eligible as long as they
                  are stable on oral antidiabetics and have either a documented glycated hemoglobin
                  (HbA1c) of ≤ 8 % within three months prior to trial participation or confirmation
                  of controlled blood glucose level must be obtained at the SCR (screening) visit
                  by a lab test.

               -  Subjects who receive short term treatment for temporary conditions.

               -  Other clinically insignificant findings not deemed to be associated with
                  increased risk for respiratory viral infections as determined by the
                  investigator.

          4. Able to comply with trial requirements; including access to transportation for trial
             visits.

          5. Body mass index (BMI) ≥ 18.5 and ≤ 39.9

             BMI formula for pounds and inches:

             BMI = (bodyweight in pounds) * 703 (bodyheight in inches)2

          6. Women of childbearing potential (WOCBP) must have used an acceptable method of
             contraception for at least 30 days prior to the first vaccination, must agree to use
             an acceptable method of contraception (as defined in Section 8.2.11) during the trial,
             and must avoid becoming pregnant for at least 28 days after the last vaccination.
             WOCBP must have a negative serum pregnancy test at screening and a negative urine
             pregnancy test prior to each vaccination

          7. Not clinically significant laboratory values as defined in the protocol, excluding any
             Grade ≥ 3 toxicity.

          8. Negative human immunodeficiency virus antibody test (anti-HIV), negative hepatitis B
             surface antigen (HBsAG) and negative antibody test to hepatitis C virus.

          9. Electrocardiogram (ECG) without clinically significant acute findings (e.g. findings
             suggestive of current ischemia, ventricular arrhythmias, congestive heart failure and
             ventricular hypertrophy).

        Exclusion Criteria (Main Study):

          1. Pregnant or breast-feeding women.

          2. Uncontrolled serious infection, i.e. not responding to antimicrobial therapy.

          3. History or current clinical manifestation of any serious medical condition, which in
             the opinion of the investigator would compromise the safety of the subject or would
             limit the subject's ability to complete the trial.

               -  History of cerebrovascular disorders, including stroke. Patients with history of
                  transient ischaemic attack (TIA) ≥ 1 year prior to trial participation remain
                  eligible.

               -  History of myocardial infarction within ≤ 1 year prior to trial participation,
                  current clinical manifestation of angina pectoris, current clinical manifestation
                  of congestive heart failure ≥ New York Heart Association (NYHA) Grade II,
                  uncontrolled high blood pressure defined as systolic blood pressure ≥ 150 mmHg
                  and/or diastolic ≥ 100 mmHg within the last 2 months.

          4. History of or active autoimmune disease. Persons with vitiligo or thyroid disease
             taking thyroid replacement are not excluded. Persons with rheumatoid arthritis not
             requiring immunomodulatory and/or immunosuppressant treatment are not excluded.

          5. Known or suspected impairment of immunologic functions including, but not limited to
             chronic inflammatory bowel disorders, diabetes mellitus type I.

          6. History of malignancy other than squamous cell or basal cell skin cancer, unless there
             has been surgical excision at least 6 months ago that is considered to have achieved
             cure. Subjects with history of skin cancer should not be vaccinated at the previous
             tumor site.

          7. Clinically significant mental disorder, not adequately controlled by medical
             treatment.

          8. Active or recent (within the time period of six months before trial participation)
             history of chronic alcohol abuse and/or intravenous and/or nasal drug abuse.

          9. 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.

         10. Known allergy to eggs or aminoglycosides.

         11. History of anaphylaxis or severe allergic reaction to any vaccine.

         12. Having received any vaccinations or planned vaccinations with a live vaccine within 30
             days prior to or after trial vaccination.

         13. Having received any vaccinations or planned vaccinations with an inactivated vaccine
             within 14 days prior to or after trial vaccination.

         14. Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone
             (or equivalent)/day or any other immune-modifying drugs during a period starting from
             three months prior to first administration of the trial vaccination and ending at the
             last visit of the active trial phase. The use of topical, inhaled, ophthalmic and
             nasal glucocorticoids is permitted.

         15. Administration or planned administration of immunoglobulins and/or any blood products
             during a period starting from three months prior to first administration of the trial
             vaccination and ending at the last visit of the active trial phase.

         16. Use of any investigational or non-registered drug or vaccine other than the trial
             vaccine within 30 days preceding the first trial vaccination, or planned
             administration of such a drug between participation in the trial and until 4 weeks
             after last trial vaccination.

         17. Previous or planned vaccination with a RSV vaccine/vaccine candidate.

         18. Clinical trial personnel working on the current trial.

        Inclusion Criteria (Substudy):

          1. Prior to performance of any booster substudy specific procedures, the subject has
             read, signed and dated an informed consent form, having been advised of the risks and
             benefits of the trial in a language understood by the subject.

          2. Subject has completed all vaccinations of the main trial according to protocol.

        Exclusion Criteria (Substudy):

          1. Any condition that, in the opinion of the investigator, makes it unsafe for the
             subject to receive a further vaccination.

          2. Pregnancy.

          3. An anaphylactic reaction following the administration of any vaccine(s).

          4. Clinical need for concomitant or ancillary therapy not permitted in the trial as
             outlined in Protocol Section 8.2.2.

          5. Having received any vaccinations or planned vaccinations with a live vaccine within 30
             days prior to or after booster vaccination.

          6. Having received any vaccinations or planned vaccinations with an inactivated vaccine
             within 14 days prior to or after booster vaccination.

          7. Chronic systemic administration (defined as more than 14 days) of > 5 mg prednisone
             (or equivalent)/day or any other immune-modifying drugs during a period starting from
             3 months prior to administration of the booster vaccine and ending at the last visit
             of the booster active trial phase. The use of topical, inhaled, ophthalmic and nasal
             glucocorticoids is permitted.

          8. Administration or planned administration of immunoglobulins and/or any blood products
             during a period starting from 3 months prior to administration of the booster vaccine
             and ending at the last visit of the booster active trial phase.

          9. Use of any investigational or non-registered drug or vaccine other than the trial
             vaccine within 30 days preceding the booster vaccination, or planned administration of
             such a drug during participation in the booster substudy and until 4 weeks after
             booster vaccination.

         10. Subject's request to discontinue

         11. Subject's refusal to receive booster vaccination.

         12. Subject unwilling or unable to comply with trial requirements. Any reason that, in the
             opinion of the investigator contradicts administration of the booster vaccination or
             otherwise requires early discontinuation of a subject.