Respiratory Syncytial Virus Prevention
Conditions
Brief summary
The purpose of this study is to demonstrate non-inferiority in terms of humoral immune responses induced by vaccination with one dose of the Phase 3 clinical trial material (CTM) compared with one dose of the Phase 2b CTM.
Interventions
BIOLOGICALAd26.RSV.preF-based vaccine
Ad26.RSV.preF-based vaccine will be administered as a single intramuscular injection.
Sponsors
Janssen Vaccines & Prevention B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to adhere to the prohibitions and restrictions specified in the protocol * Before randomization, a participant must be postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and not intending to conceive by any methods * In the investigator's clinical judgment, participant must be in stable health at the time of vaccination. Participants may have underlying illnesses such as hypertension, congestive heart failure, chronic obstructive pulmonary disease, type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider. Participants will be included on the basis of medical history, and vital signs performed between informed consent form (ICF) signature and vaccination * Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study * From the time of vaccination through 3 months after vaccination, agrees not to donate blood
Exclusion criteria
* Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine) * Abnormal function of the immune system resulting from clinical condition or medication * History of acute polyneuropathy (example, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy * History of thrombosis with thrombocytopenia syndrome (TTS) or heparin-induced thrombocytopenia and thrombosis (HITT) * Has had major surgery (per the investigator's judgment) within 4 weeks before administration of the study vaccine or will not have recovered from surgery per the investigator's judgment at time of vaccination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination | 14 days post vaccination on Day 1 (Day 15) | GMTs of pre-F antibodies as assessed by ELISA at 14 days post administration of Ad26/protein preF RSV based vaccine were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination | Up to Day 7 post vaccination on Day 1 (up to Day 8) | Number of participants with solicited local AEs 7 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site). |
| Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination | Up to Day 7 post vaccination on Day 1 (up to Day 8) | Number of participants with solicited systemic AEs 7 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days). |
| Number of Participants With Unsolicited AEs for 28 Days Post Vaccination | Up to Day 28 post vaccination on Day 1 (up to Day 29) | Number of participants with unsolicited AEs 28 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary. |
| Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination | From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) | Number of participants with SAEs until 6 months post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. |
| Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination | From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183) | Number of participants with AESIs until 6 months post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI. |
| Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination | 14 days post vaccination on Day 1 (Day 15) | RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay at 14 days post administration of Ad26/protein preF RSV based vaccine were expressed as 50 percent (%) inhibitory concentration (IC50) units. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg Participants received a single intramuscular (IM) injection of adenovirus serotype 26 pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) 1.0\*10\^11 viral particles (vp) and respiratory syncytial virus prefusion F-protein (RSV preF) 150 micrograms (mcg) based vaccine mixture (Ad26/protein preF RSV) on Day 1, which was a representative of Phase 3 clinical trial material (CTM). | 123 |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg Participants received a single IM injection of Ad26.RSV.preF 1.0\*10\^11 vp and RSV preF protein 150 mcg based vaccine mixture (Ad26/protein preF RSV) on Day 1, which was a representative of Phase 2b CTM. | 125 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Randomized but not vaccinated | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Total | Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg |
|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 4.34 | 64 years STANDARD_DEVIATION 4.1 | 63.8 years STANDARD_DEVIATION 3.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants | 103 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 143 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 26 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 111 Participants | 220 Participants | 109 Participants |
| Region of Enrollment UNITED STATES | 125 Participants | 248 Participants | 123 Participants |
| Sex: Female, Male Female | 63 Participants | 128 Participants | 65 Participants |
| Sex: Female, Male Male | 62 Participants | 120 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 123 | 1 / 125 |
| other Total, other adverse events | 3 / 123 | 2 / 125 |
| serious Total, serious adverse events | 2 / 123 | 3 / 125 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination
GMTs of pre-F antibodies as assessed by ELISA at 14 days post administration of Ad26/protein preF RSV based vaccine were reported.
Time frame: 14 days post vaccination on Day 1 (Day 15)
Population: The per-protocol immunogenicity (PPI) set included all randomized participants who received the study vaccine, and for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination | 5054 ELISA units per liter (EU/L) |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Geometric Mean Titers (GMTs) of Prefusion F-protein (preF) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) 14 Days Post Vaccination | 4836 ELISA units per liter (EU/L) |
Secondary
Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination
Number of participants with AESIs until 6 months post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI.
Time frame: From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183)
Population: The FAS included all participants who received study vaccination, regardless of the occurrence of protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination | 0 Participants |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Adverse Event of Special Interests (AESIs) Until 6 Months Post Vaccination | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination
Number of participants with SAEs until 6 months post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: From Day 1 up to 6 months post vaccination on Day 1 (up to Day 183)
Population: The FAS included all participants who received study vaccination, regardless of the occurrence of protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination | 2 Participants |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Serious Adverse Events (SAEs) Until 6 Months Post Vaccination | 3 Participants |
Secondary
Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination
Number of participants with solicited local AEs 7 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site).
Time frame: Up to Day 7 post vaccination on Day 1 (up to Day 8)
Population: The full analysis set (FAS) included all participants who received study vaccination, regardless of the occurrence of protocol deviations. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination | 84 Participants |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days Post Vaccination | 74 Participants |
Secondary
Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination
Number of participants with solicited systemic AEs 7 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).
Time frame: Up to Day 7 post vaccination on Day 1 (up to Day 8)
Population: The FAS included all participants who received study vaccination, regardless of the occurrence of protocol deviations. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination | 76 Participants |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Solicited Systemic AEs for 7 Days Post Vaccination | 77 Participants |
Secondary
Number of Participants With Unsolicited AEs for 28 Days Post Vaccination
Number of participants with unsolicited AEs 28 days post vaccination on Day 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary.
Time frame: Up to Day 28 post vaccination on Day 1 (up to Day 29)
Population: The FAS included all participants who received study vaccination, regardless of the occurrence of protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Unsolicited AEs for 28 Days Post Vaccination | 9 Participants |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Number of Participants With Unsolicited AEs for 28 Days Post Vaccination | 12 Participants |
Secondary
Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination
RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay at 14 days post administration of Ad26/protein preF RSV based vaccine were expressed as 50 percent (%) inhibitory concentration (IC50) units.
Time frame: 14 days post vaccination on Day 1 (Day 15)
Population: The PPI set included all randomized participants who received the study vaccine, and for whom immunogenicity data were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group 1 (Phase 3 CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination | 7710 Titers |
| Group 2 (Phase 2b CTM): Ad26.RSV.preF 1.0*10^11 vp + RSV preF Protein 150 mcg | Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination | 7256 Titers |