Respiratory Syncytial Virus Infections
Conditions
Brief summary
Phase 3 randomized, double blind study comparing recombinant MVA-BN-RSV vaccine vs placebo for efficacy and safety in adults \>=60 years of age
Interventions
BIOLOGICALMVA-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.
BIOLOGICALTris Buffered Saline (TBS)
One injection, solution for injection, intramuscular use, 0.5mL TBS, pH 7.7.
Sponsors
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of PCR Confirmed RSV-associated LRTD With at Least 3 Symptoms | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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) |
| Occurrence of PCR Confirmed RSV-associated LRTD With at Least 2 Symptoms | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Hospitalization Due to Confirmed RSV Disease or Due to Any Complication Related to RSV-confirmed Respiratory Disease | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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. |
| Occurrence of Severe PCR Confirmed RSV-associated LRTD | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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 |
| Number of Participants With Serious Adverse Events | From vaccination through study termination, up to 16 months | Number and percentage of study participants reporting any serious adverse events at any time during the trial period. |
| Number of Participants With Grade 3 or Higher Adverse Events | Within 29 days after vaccination | Number and percentage of study participants reporting any grade 3 or higher unsolicited adverse events assessed as related to study vaccine |
| Number of Participants With Solicited Local Adverse Events | Within 8 days after vaccination | 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. |
| Occurrence of PCR Confirmed RSV-associated ARD | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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) |
| Number of Participants With Unsolicited Adverse Events | Within 29 days after vaccination | Number and percentage of study participants reporting any unsolicited adverse events within 29 days after vaccination. |
| RSV-specific T-cell Responses | 1 week after vaccination | RSV-specific T-cell responses measured 1 week post vaccination in a subset of the study population |
| RSV-specific Serum IgG Antibody Titers | 2 weeks after vaccination | Geometric Mean Titers (GMTs) based on RSV-specific Immunoglobulin G (IgG) Enzyme-linked Immunosorbent Assay (ELISA) |
| RSV-specific Serum Neutralizing Antibody Titers (Subtype A) | 2 weeks after vaccination | 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 |
| RSV-specific Serum Neutralizing Antibody Titers (Subtype B) | 2 weeks after vaccination | 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 |
| Number of Participants With Solicited Systemic Adverse Events | Within 8 days after vaccination | 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. |
| Occurrence of Complications Related to PCR-confirmed RSV Disease | From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months | 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. |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MVA-BN-RSV Single administration of MVA-BN-RSV vaccine with a titer of at least 3 x 10E8 infectious units (Inf.U)/0.5mL (intramuscular injection) | 9,160 |
| Placebo Single administration of Tris Buffered Saline (TBS) (intramuscular injection; 0.5mL) | 9,188 |
| Total | 18,348 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Death | 38 | 32 |
| Overall Study | Lost to Follow-up | 334 | 339 |
| Overall Study | Other Reason | 669 | 690 |
| Overall Study | Physician Decision | 20 | 8 |
| Overall Study | Protocol Violation | 6 | 2 |
| Overall Study | Study terminated by Sponsor | 6,358 | 6,358 |
| Overall Study | Withdrawal by Subject | 203 | 222 |
Baseline characteristics
| Characteristic | MVA-BN-RSV | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 70.4 years STANDARD_DEVIATION 5.78 | 70.5 years STANDARD_DEVIATION 5.83 | 70.4 years STANDARD_DEVIATION 5.81 |
| Age, Customized 60 to 64 years | 931 Participants | 933 Participants | 1864 Participants |
| Age, Customized 65 to 74 years | 6166 Participants | 6164 Participants | 12330 Participants |
| Age, Customized 75 to 84 years | 1889 Participants | 1903 Participants | 3792 Participants |
| Age, Customized >= 85 years | 174 Participants | 188 Participants | 362 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 34 Participants | 26 Participants | 60 Participants |
| Race/Ethnicity, Customized Asian | 79 Participants | 63 Participants | 142 Participants |
| Race/Ethnicity, Customized Black or African American | 1185 Participants | 1202 Participants | 2387 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 9 Participants | 15 Participants | 24 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 67 Participants | 87 Participants | 154 Participants |
| Race/Ethnicity, Customized White | 7786 Participants | 7794 Participants | 15580 Participants |
| Region of Enrollment Germany | 715 Participants | 720 Participants | 1435 Participants |
| Region of Enrollment United States | 8445 Participants | 8468 Participants | 16913 Participants |
| Sex: Female, Male Female | 4606 Participants | 4680 Participants | 9286 Participants |
| Sex: Female, Male Male | 4554 Participants | 4508 Participants | 9062 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 9,389 | 34 / 9,191 |
| other Total, other adverse events | 82 / 9,389 | 82 / 9,191 |
| serious Total, serious adverse events | 517 / 9,389 | 422 / 9,191 |
Outcome results
Primary
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)
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of PCR Confirmed RSV-associated LRTD With at Least 2 Symptoms | 25 Participants |
| Placebo | Occurrence of PCR Confirmed RSV-associated LRTD With at Least 2 Symptoms | 61 Participants |
95% CI: [34.7, 74.3]
Primary
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)
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of PCR Confirmed RSV-associated LRTD With at Least 3 Symptoms | 12 Participants |
| Placebo | Occurrence of PCR Confirmed RSV-associated LRTD With at Least 3 Symptoms | 21 Participants |
95% CI: [-16.1, 71.9]
Secondary
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
Time frame: Within 29 days after vaccination
Population: Safety Set i.e., all participants who received study vaccine (MVA-BN-RSV or placebo). Subjects were analyzed based on the treatment they actually received. Subjects who received multiple doses of study vaccine (multiple enrollers) were analyzed in the MVA-BN-RSV arm when having received the MVA-BN-RSV vaccine at least once; subjects were analyzed in the placebo arm when having received placebo only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Number of Participants With Grade 3 or Higher Adverse Events | 11 Participants |
| Placebo | Number of Participants With Grade 3 or Higher Adverse Events | 2 Participants |
Secondary
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.
Time frame: From vaccination through study termination, up to 16 months
Population: Safety Set i.e., all participants who received study vaccine (MVA-BN-RSV or placebo). Subjects were analyzed based on the treatment they actually received. Subjects who received multiple doses of study vaccine (multiple enrollers) were analyzed in the MVA-BN-RSV arm when having received the MVA-BN-RSV vaccine at least once; subjects were analyzed in the placebo arm when having received placebo only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Number of Participants With Serious Adverse Events | 517 Participants |
| Placebo | Number of Participants With Serious Adverse Events | 422 Participants |
Secondary
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.
Time frame: Within 8 days after vaccination
Population: Safety Set i.e., all participants who received study vaccine (MVA-BN-RSV or placebo). Subjects were analyzed based on the treatment they actually received. Subjects who received multiple doses of study vaccine (multiple enrollers) were analyzed in the MVA-BN-RSV arm when having received the MVA-BN-RSV vaccine at least once; participants were analyzed in the placebo arm when having received placebo only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-BN-RSV | Number of Participants With Solicited Local Adverse Events | Erythema | 522 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Local Adverse Events | Induration | 417 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Local Adverse Events | Swelling | 448 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Local Adverse Events | Pruritus | 1718 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Local Adverse Events | Pain | 5704 Participants |
| Placebo | Number of Participants With Solicited Local Adverse Events | Pruritus | 470 Participants |
| Placebo | Number of Participants With Solicited Local Adverse Events | Pain | 667 Participants |
| Placebo | Number of Participants With Solicited Local Adverse Events | Erythema | 157 Participants |
| Placebo | Number of Participants With Solicited Local Adverse Events | Swelling | 78 Participants |
| Placebo | Number of Participants With Solicited Local Adverse Events | Induration | 74 Participants |
Secondary
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.
Time frame: Within 8 days after vaccination
Population: Safety Set i.e., all participants who received study vaccine (MVA-BN-RSV or placebo). Subjects were analyzed based on the treatment they actually received. Subjects who received multiple doses of study vaccine (multiple enrollers) were analyzed in the MVA-BN-RSV arm when having received the MVA-BN-RSV vaccine at least once; participants were analyzed in the placebo arm when having received placebo only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Pyrexia | 550 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Headache | 3144 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Myalgia | 4558 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Chills | 1531 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Nausea | 990 Participants |
| MVA-BN-RSV | Number of Participants With Solicited Systemic Adverse Events | Fatigue | 3526 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Nausea | 551 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Pyrexia | 309 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Chills | 490 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Headache | 1737 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Fatigue | 1973 Participants |
| Placebo | Number of Participants With Solicited Systemic Adverse Events | Myalgia | 1480 Participants |
Secondary
Number of Participants With Unsolicited Adverse Events
Number and percentage of study participants reporting any unsolicited adverse events within 29 days after vaccination.
Time frame: Within 29 days after vaccination
Population: Safety Set i.e., all participants who received study vaccine (MVA-BN-RSV or placebo). Subjects were analyzed based on the treatment they actually received. Subjects who received multiple doses of study vaccine (multiple enrollers) were analyzed in the MVA-BN-RSV arm when having received the MVA-BN-RSV vaccine at least once; subjects were analyzed in the placebo arm when having received placebo only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Number of Participants With Unsolicited Adverse Events | 607 Participants |
| Placebo | Number of Participants With Unsolicited Adverse Events | 581 Participants |
Secondary
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.
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of Complications Related to PCR-confirmed RSV Disease | 0 Participants |
| Placebo | Occurrence of Complications Related to PCR-confirmed RSV Disease | 1 Participants |
Secondary
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.
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of Hospitalization Due to Confirmed RSV Disease or Due to Any Complication Related to RSV-confirmed Respiratory Disease | 0 Participants |
| Placebo | Occurrence of Hospitalization Due to Confirmed RSV Disease or Due to Any Complication Related to RSV-confirmed Respiratory Disease | 1 Participants |
Secondary
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)
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of PCR Confirmed RSV-associated ARD | 42 Participants |
| Placebo | Occurrence of PCR Confirmed RSV-associated ARD | 82 Participants |
95% CI: [25.8, 64.7]
Secondary
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
Time frame: From 14 days post-vaccination up to the end of one RSV season, up to a maximum of 11 months
Population: Full Analysis Set i.e., all participants who were randomized to any treatment arm and received study vaccine (MVA-BN-RSV or placebo). Participants were analyzed based on the treatment to which they were randomized. Participants who received multiple doses of study vaccine (multiple enrollers) were included once in this analysis set with group allocation based on their first randomization and with data censored from the time of second randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MVA-BN-RSV | Occurrence of Severe PCR Confirmed RSV-associated LRTD | 0 Participants |
| Placebo | Occurrence of Severe PCR Confirmed RSV-associated LRTD | 2 Participants |
Secondary
RSV-specific Serum IgG Antibody Titers
Geometric Mean Titers (GMTs) based on RSV-specific Immunoglobulin G (IgG) Enzyme-linked Immunosorbent Assay (ELISA)
Time frame: 2 weeks after vaccination
Population: Immunogenicity Analysis Set, a subset of the Full Analysis Set, including participants at designated clinical trial sites who signed the informed consent form for collection of serum samples. Number of participants analyzed represent the participants with antibody titer results available at the respective time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MVA-BN-RSV | RSV-specific Serum IgG Antibody Titers | Week 2 | 4335.5 Titer |
| MVA-BN-RSV | RSV-specific Serum IgG Antibody Titers | Baseline | 1510.6 Titer |
| Placebo | RSV-specific Serum IgG Antibody Titers | Baseline | 1590.1 Titer |
| Placebo | RSV-specific Serum IgG Antibody Titers | Week 2 | 1562.9 Titer |
Secondary
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
Time frame: 2 weeks after vaccination
Population: Immunogenicity Analysis Set, a subset of the Full Analysis Set, including participants at designated clinical trial sites who signed the informed consent form for collection of serum samples. Number of participants analyzed represent the participants with antibody titer results available at the respective time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MVA-BN-RSV | RSV-specific Serum Neutralizing Antibody Titers (Subtype A) | Baseline | 275.1 Titer |
| MVA-BN-RSV | RSV-specific Serum Neutralizing Antibody Titers (Subtype A) | Week 2 | 482.3 Titer |
| Placebo | RSV-specific Serum Neutralizing Antibody Titers (Subtype A) | Baseline | 310.6 Titer |
| Placebo | RSV-specific Serum Neutralizing Antibody Titers (Subtype A) | Week 2 | 307.7 Titer |
Secondary
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
Time frame: 2 weeks after vaccination
Population: Immunogenicity Analysis Set, a subset of the Full Analysis Set, including participants at designated clinical trial sites who signed the informed consent form for collection of serum samples. Number of participants analyzed represent the participants with antibody titer results available at the respective time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| MVA-BN-RSV | RSV-specific Serum Neutralizing Antibody Titers (Subtype B) | Baseline | 289.5 Titer |
| MVA-BN-RSV | RSV-specific Serum Neutralizing Antibody Titers (Subtype B) | Week 2 | 475.3 Titer |
| Placebo | RSV-specific Serum Neutralizing Antibody Titers (Subtype B) | Baseline | 336.5 Titer |
| Placebo | RSV-specific Serum Neutralizing Antibody Titers (Subtype B) | Week 2 | 307.6 Titer |
Secondary
RSV-specific T-cell Responses
RSV-specific T-cell responses measured 1 week post vaccination in a subset of the study population
Time frame: 1 week after vaccination