Upper and lower respiratory tract infections caused by Respiratory Syncytical Virus MedDRA version: 20.0 Level: LLT Classification code 10039247 Term: RSV infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: MVA-BN-RSV
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: MVA-BN-RSV
Other descriptive name: MVA-BN-RSV
Sponsors
Bavarian Nordic A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study. 2. Male or female, between 18 and 55 years old (extremes included) at screening. 3. General good health, without clinically relevant medical illness, physical exam findings, or laboratory abnormalities, as determined by the investigator. 4. Willing to adhere to the prohibitions and restrictions specified in this protocol, including willingness to stay confined to the CPU for the required duration. 5. Willingness to have samples stored for future research to investigate vaccine and RSV associated changes in immunity. 6. Absent or low levels of pre-existing RSV neutralizing antibodies, as determined by PRNT° Strain A assay (= 30 % of average population). 7. Female subjects should fulfil one of the following criteria: a. At least 1 year post-menopausal (amenorrhea >12 months and/or follicle-stimulating hormone >according to local lab values mIU/mL) prior to screening; b. Surgically sterile (bilateral oophorectomy, hysterectomy); c. Will use contraceptives as outlined in inclusion criterion 8 from screening to discharge. 8. Female subjects of childbearing potential and male subjects who are sexually active with a female partner of childbearing potential must agree to the use of an effective method of birth control from at least 30 days prior to administration of the MVA-BN-RSV vaccine to until 30 days after virus inoculation with the challenge virus. Note: medically acceptable methods of contraception that may be used by the subject and/or partner include combined double barrier method, oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, abstinence, sterilization, tubal ligation and vasectomy. 9. Female subject has a negative pregnancy test at screening and admission to the CPU for virus inoculation. Note: Pregnancy testing will consist of a serum (beta-)human chorionic gonadotropin (HCG) test at screening and admission to the CPU and urine pregnancy tests at other visits, in all women of childbearing potential (WOCBP). 10. Negative hepatitis panel (including hepatitis B surface antigen and anti-hepatitis C virus antibodies) and negative human immunodeficiency virus antibody and antigen screens at screening. 11. Troponin I within normal limits Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 72 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Has an acute or chronic medical condition that, in the opinion of the investigator, would render the study procedures unsafe or would interfere with the evaluation of the responses, including but not limited to, neurologic, cardiovascular, respiratory, hepatic, hematologic, rheumatologic, endocrine, gastrointestinal, renal, autoimmune, or immune suppression conditions. 2. Laboratory parameters (such as complete or full blood count (CBC/FBC), serum biochemistry including aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphokinase (ALP), bilirubin, or creatinine values), pulse rate and/or blood pressure, or ECG outside normal range and deemed clinically relevant by the investigator. 3. Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the trial protocol. 4. A medical, occupational, or family problem as a result of alcohol or illicit drug use during the 12 months prior to screening. 5. Routine smoker (>4 cigarettes or other tobacco-based products per week) of a tobacco product or marijuana currently or in the past year prior to screening. 6. Current alcohol abuse or addiction (positive alcohol breath test at screening or upon check-in at the clinical site). Excessive use of alcohol is an intake of >21 units per week for males and >14 units per week for females where one alcohol unit is defined as 10 mL or 8 g of pure alcohol. A single unit is equal to one 25 mL (single) measure of whisky (alcohol by volume [ABV] 40%), or a third of a pint of beer (190 mL; ABV 5-6%) or half a standard (175 mL) glass of wine (ABV 12%). 7. Current illicit drug abuse (positive drug screen for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates at screening or upon admission to the clinical site) or addiction. 8. Presence of any febrile illness (=38.0°C oral) or symptoms suggestive of a viral respiratory infection within 2 weeks prior to vaccination. 9. Subjects with a positive result on below-listed adventitious agent screening (qualitative PCR testing) within 2 days prior to virus inoculation (i.e., at admission to the CPU): Subjects will be excluded in case of a positive result for: influenza A, influenza B, RSV, Bordetella pertussis, Chlamydophila pneumoniae or Mycoplasma pneumoniae. 10. Use of corticosteroids (including nasal preparations) or immunosuppressive drugs within 30 days before vaccination and ending at the last visit of the active trial phase. Topical corticosteroids are allowed. 11. A history of anaphylaxis. 12. 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, eggs or aminoglycosides) or challenge agent. 13. A history of asthma within the past 10 years prior to screening, or a current diagnosis of asthma or reactive airway disease associated with exercise or allergic rhinitis, with the exception of seasonal hay fever, house dust mite or allergy to animals. 14. Chronic Obstructive Airways Disease or any respiratory illness associated with reduced lung capacity or capability. 15. A know
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the effect of vaccination with MVA-BN-RSV vaccine on RSV viral load area under the curve (AUC) by quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasopharyngeal swabs in healthy subjects after virus inoculation with a wild-type RSV A challenge virus;Primary end point(s): The primary efficacy endpoint in this study is to compare the AUC of the RSV RNA log10 viral load determined by qRT-PCR from RSV A virus inoculation until discharge (11 days after virus inoculation) between the active vaccine group and the placebo group.; Secondary Objective: -Assess the immunological responses over the study period -Assess the safety, tolerability and reactogenicity . -Assess the effect of IMP vaccination on RSV clinical signs and symptoms over time via time to start, peak, and cessation of RSV symptoms ) and RSV composite symptom score AUC after virus inoculation with a wild-type RSV A challenge virus. -Assess the difference btw the active vaccine and the placebo group in viral load AUC by quantitative RSV culture (qCulture) from nasopharyngeal swabs after virus inoculation with a wild-type RSV A challenge virus. -Assess the effects of IMP vaccination on viral shedding over time via descriptive statistics of the viral load AUC by qRT-PCR and by qCulture, and time to start, peak, and cessation of viral shedding (qRT-PCR and qCulture) after virus inoculation with a wild-type RSV A challenge virus. -Assess the effect of IMP vaccination on nasal mucus weight after virus inoculation with a wild-type RSV A challenge virus. ;Timepoint(s) of evaluation of this end point: 11 days after virus inoculation (challenge) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 11 days after virus inoculation (challenge) ; Secondary end point(s): Efficacy (post virus inoculation with a wild-type RSV A challenge virus) • Attack Rate: Attack rate will be defined as percentage of inoculated subjects with at least 2 consecutive NP swabs positive for RSV (shedding events) determined by qRT-PCR; • Viral load AUC by qRT-PCR from NP swabs from virus inoculation until discharge (11 days after virus inoculation); • Viral load AUC by qCulture from NP swabs from virus inoculation until discharge (11 days after virus inoculation); • Composite symptom score AUC based on the symptom score card from virus inoculation until discharge (11 days after virus inoculation); • Time to start and duration of viral shedding (RSV qRT-PCR); • Time to start and duration of viral shedding (RSV qCulture); • Time to start and duration of RSV sign and symptoms (symptom score card); • RSV challenge-associated clinical disease: frequency of upper respiratory infection, lower respiratory infection and individual symptom assessment; • Nasal mucus weight based on tissue paper collection. Safety (post vaccination with MVA-BN-RSV and post virus inoculation with a wild-type RSV A challenge virus) • Occurrence, relationship to the trial vaccine and severity of any serious adverse event (SAE); • Occurrence, relationship to the virus inoculation and severity of any SAE; • Occurrence of any grade 3 or higher adverse event (AE) at least possibly related to the trial vaccine within 4 weeks after vaccination but prior to inoculation; • Occurrence of any grade 3 or higher AE at least possibly related to virus inoculation with onset after virus inoculation until approximately 4 weeks post inoculation (Follow- | — |
Countries
Belgium
Contacts
Public ContactElke Jordan
Bavarian Nordic GmbH
Outcome results
None listed