Clinical trial NCT02873286: RSV-MVA-BN Vaccine Phase II Trial in ≥ 55 Year Old Adults
Official title: A Randomized, Single-blind, Placebo Controlled, Dose-ranging Phase II Trial in ≥ 55 Year Old Adults to Evaluate the Safety and Immunogenicity of the Recombinant MVA-BN-RSV Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: RSV Vaccines
Respiratory Syncytial Virus Vaccines
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2016-08-19
Enrollment: 420
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Primary outcomes:
measure: PRNT (Subtype A) GMT
timeFrame: Week 6 (Main Study) i.e., 2 weeks following the second vaccination
Secondary outcomes:
measure: PRNT (Subtype A) GMT
timeFrame: within 108 weeks
measure: Percentage of Participants With Response by PRNT (Subtype A)
timeFrame: within 108 weeks
measure: PRNT (Subtype B) GMT
timeFrame: within 108 weeks
measure: Percentage of Participants With Response by PRNT (Subtype B)
timeFrame: within 108 weeks
measure: ELISA (IgG) GMT
timeFrame: within 108 weeks
measure: Percentage of Participants With Response by IgG ELISA
timeFrame: within 108 weeks
measure: ELISA (IgA) GMT
timeFrame: within 108 weeks
measure: Percentage of Participants With Response by IgA ELISA
timeFrame: within 108 weeks
measure: ELISA (Mucosal IgA) GMT
timeFrame: within 82 weeks
measure: Percentage of Participants With Response by Mucosal IgA ELISA
timeFrame: within 82 weeks
measure: ELISPOT (IFN-g, Peptide Pool: F) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IFN-g, Peptide Pool: G(A)) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IFN-g, Peptide Pool: G(B)) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IFN-g, Peptide Pool: M2) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IFN-g, Peptide Pool: N) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IL-4, Peptide Pool: F) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IL-4, Peptide Pool: G(A)) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IL-4, Peptide Pool: G(B)) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IL-4, Peptide Pool: M2) GMSFU
timeFrame: within 58 weeks
measure: ELISPOT (IL-4, Peptide Pool: N) GMSFU
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: F)
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: G(A))
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: G(B))
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: M2)
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IFN-g, Peptide Pool: N)
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: F)
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: G(A))
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: G(B))
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: M2)
timeFrame: within 58 weeks
measure: Percentage of Participants With Response by ELISPOT (IL-4, Peptide Pool: N)
timeFrame: within 58 weeks
measure: Memory B Cells (IgG) GMSFU
timeFrame: within 82 weeks
measure: Serious Adverse Events
timeFrame: within 108 weeks (Main Study + Booster Substudy)
measure: Related Serious Adverse Events
timeFrame: within 108 weeks (Main Study + Booster Substudy)
measure: Grade ≥ 3 Serious Adverse Events
timeFrame: within 108 weeks (Main Study + Booster Substudy)
measure: Related Grade ≥ 3 Adverse Events
timeFrame: within 29 days after vaccination
measure: Solicited Local Adverse Events
timeFrame: within 8 days after vaccination
measure: Grade ≥ 3 Solicited Local Adverse Events
timeFrame: within 8 days after vaccination
measure: Solicited General Adverse Events
timeFrame: within 8 days after vaccination
measure: Grade ≥ 3 Solicited General Adverse Events
timeFrame: within 8 days after vaccination
measure: Related Solicited General Adverse Events
timeFrame: within 8 days after vaccination
measure: Unsolicited Non-serious Adverse Events
timeFrame: within 29 days after vaccination
measure: Related Unsolicited Non-serious Adverse Events
timeFrame: within 29 days after vaccination
measure: Grade ≥ 3 Unsolicited Non-serious Adverse Events
timeFrame: within 29 days after vaccination
Other outcomes:
Locations:
city: Redding
country: United States
facility: Paradigm Research
state: California
city: San Diego
country: United States
facility: Optimal Research
state: California
city: The Villages
country: United States
facility: Compass Research
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Peoria
country: United States
facility: Optimal Research
state: Illinois
city: Rockville
country: United States
facility: Optimal Research
state: Maryland
city: Saint Louis
country: United States
facility: Washington University in St. Louis, School of Medicine
state: Missouri
city: Binghamton
country: United States
facility: United Medical Associates
state: New York
city: Endwell
country: United States
facility: Regional Clinical Research Associates
state: New York
city: Cleveland
country: United States
facility: Rapid Medical Research
state: Ohio
city: Fort Worth
country: United States
facility: Ventavia Research Group
state: Texas
Study officials:
affiliation: Washington University School of Medicine
name: Steven Lawrence, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jordan E, Lawrence SJ, Meyer TPH, Schmidt D, Schultz S, Mueller J, Stroukova D, Koenen B, Gruenert R, Silbernagl G, Vidojkovic S, Chen LM, Weidenthaler H, Samy N, Chaplin P. Broad Antibody and Cellular Immune Response From a Phase 2 Clinical Trial With a Novel Multivalent Poxvirus-Based Respiratory Syncytial Virus Vaccine. J Infect Dis. 2021 Mar 29;223(6):1062-1072. doi: 10.1093/infdis/jiaa460.