A Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of an Ad26.RSV.preF-based Vaccine in the Prevention of Lower Respiratory Tract Disease Caused by RSV in Adults Aged 60 Years and Older
COMPLETED - HAS RESULTS
(See Contacts and Locations) Verified February 2024 by Janssen Vaccines & Prevention B.V.
Sponsor
Janssen Vaccines & Prevention B.V.
Information Provided by (Responsible Party)
Janssen Vaccines & Prevention B.V.
Clinicaltrials.gov Identifier
NCT04908683 Other Study ID Numbers: CR108959 First Submitted: May 27, 2021 First Posted: June 1, 2021 Results First Posted: February 8, 2024 Last Update Posted: February 8, 2024 Last Verified: February 2024 History of Changes
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Participant met eligibility criteria but were not needed
3
1
Physician Decision
44
35
Technical problems
12
9
Withdrawal by legally authorized representative
1
Array
Protocol Violation
2
Array
Withdrawal by Subject
1188
570
Site Closure by Sponsor
6
3
Adverse Event
21
11
Death
101
61
Sponsor's decision
14398
7205
Other
92
50
Randomized not vaccinated
108
52
Baseline Characteristics
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Total
Overall Number of Baseline Participants
16709
8367
25076
Age, Continuous | Measure Type: Mean | Unit of measure: years
Number Analyzed
16709 years
8367 years
25076 years
70.2 (0.4%)
70.2 (0.8%)
70.2 (0.3%)
Age, Customized | Measure Type: Count of Participants | Unit of measure: Participants
Number Analyzed
16709 participants
8367 participants
25076 participants
Adults (60-64 years)
1472 (8.8%)
740 (8.8%)
2212 (8.8%)
From 65 to 84 years
15053 (90.1%)
7534 (90%)
22587 (90.1%)
85 years and over
184 (1.1%)
93 (1.1%)
277 (1.1%)
Sex/Gender, Customized | Measure Type: Count of Participants | Unit of measure: Participants
Number Analyzed
16709 participants
8367 participants
25076 participants
Female
9063 (54.2%)
4452 (53.2%)
13515 (53.9%)
Male
7645 (45.8%)
3913 (46.8%)
11558 (46.1%)
Others
1 (0%)
2 (0%)
3 (0%)
Ethnicity (NIH/OMB) | Measure Type: Count of Participants | Unit of measure: Participants
Number Analyzed
16709 participants
8367 participants
25076 participants
Hispanic or Latino
1555 (9.3%)
741 (8.9%)
2296 (9.2%)
Not Hispanic or Latino
14903 (89.2%)
7496 (89.6%)
22399 (89.3%)
Unknown or Not Reported
251 (1.5%)
130 (1.6%)
381 (1.5%)
Race (NIH/OMB) | Measure Type: Count of Participants | Unit of measure: Participants
Number Analyzed
16709 participants
8367 participants
25076 participants
American Indian or Alaska Native
58 (0.3%)
17 (0.2%)
75 (0.3%)
Asian
1757 (10.5%)
897 (10.7%)
2654 (10.6%)
Native Hawaiian or Other Pacific Islander
98 (0.6%)
49 (0.6%)
147 (0.6%)
Black or African American
1820 (10.9%)
935 (11.2%)
2755 (11%)
White
12649 (75.7%)
6297 (75.3%)
18946 (75.6%)
More than one race
189 (1.1%)
101 (1.2%)
290 (1.2%)
Unknown or Not Reported
138 (0.8%)
71 (0.8%)
209 (0.8%)
Outcome Measures
Primary Outcome
Title
Number of Participants With First Occurrence of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV) Mediated Lower Respiratory Tract Disease (LRTD)
Description
Number of participants with first occurrence of RT-PCR-confirmed RSV mediated LRTD according to protocol defined criteria were reported. A participant was considered to have RT-PCR-confirmed RSV-mediated LRTD if the following criteria were met: new onset or worsening from baseline of 3 or more of the symptoms as captured on the respiratory infection intensity and impact questionnaire (RiiQ, version 2) at the same assessment time point: cough, short of breath, coughing up phlegm (sputum), and wheezing and confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample. RiiQ symptom scale was a 13-item questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total LRTD symptom score was calculated as the mean of the 4 lower respiratory scores (cough, short of breath, coughing up phlegm [sputum] and wheezing).
Time Frame
From Baseline (Day 1) up to 12 months
Analysis Population Description
Per-protocol efficacy (PPE) population included all randomized and vaccinated participants, excluding those with major protocol deviations (MPDs) expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
16263
8152
Count of Participants | Unit of Measure: Participants
44
63
Secondary Outcome
Title
Number of Participants With First Occurrence of Any RT-PCR-Confirmed RSV-mediated Acute Respiratory Infection (ARI)
Description
A participant was considered to have RT-PCR-confirmed RSV-mediated ARI if the following protocol defined criteria were met: ARI episode initiated by the participant and confirmed by the site with symptoms consistent with an ARI (new symptoms or worsening from baseline of at least one of the symptoms as captured on the RiiQ): sore throat, nasal congestion, cough, short of breath, coughing up phlegm (sputum), wheezing and confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total ARI symptom score was calculated as the mean of the 4 lower respiratory scores (cough, short of breath, coughing up phlegm [sputum] and wheezing).
Time Frame
From Baseline (Day 1) up to 12 months
Analysis Population Description
PPE population included all randomized and vaccinated participants, excluding those with MPDs expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
16263
8152
Count of Participants | Unit of Measure: Participants
77
101
Secondary Outcome
Title
Number of Participants With First Occurrence of RT-PCR-Confirmed RSV Mediated LRTD During the Second Year
Description
Number of participants with first occurrence of any RT-PCR-confirmed RSV mediated LRTD during the second year were reported. A participant was considered to have RT-PCR-confirmed RSV-mediated LRTD if the following criteria were met: new onset or worsening from baseline of 3 or more of the symptoms as captured on the RiiQ, version 2 at the same assessment time point: cough, short of breath, coughing up phlegm (sputum), and wheezing and confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total LRTD symptom score was calculated as the mean of the 4 lower respiratory scores (cough, short of breath, coughing up phlegm [sputum] and wheezing).
Time Frame
From Month 12 up to Month 24
Analysis Population Description
PPE population included all randomized and vaccinated participants, excluding those with MPDs expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
10031
5011
Count of Participants | Unit of Measure: Participants
16
29
Secondary Outcome
Title
Number of Participants With First Occurrence of Any RT-PCR-Confirmed RSV Mediated ARI During the Second Year
Description
A participant was considered to have RT-PCR-confirmed RSV-mediated ARI according to protocol defined criteria were reported. A participant was considered to have RT-PCR-confirmed RSV-mediated ARI if the following criteria were met: ARI episode initiated by the participant and confirmed by the site with symptoms consistent with an ARI (new symptoms or worsening from baseline of at least one of the symptoms as captured on the RiiQ): sore throat, nasal congestion, cough, short of breath, coughing up phlegm (sputum), wheezing and confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total ARI symptom score was calculated as the mean of the 4 lower respiratory scores (cough, short of breath, coughing up phlegm [sputum] and wheezing).
Time Frame
From Month 12 up to Month 24
Analysis Population Description
PPE population included all randomized and vaccinated participants, excluding those with MPDs expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
10031
5011
Count of Participants | Unit of Measure: Participants
39
44
Secondary Outcome
Title
Number of Participants With First Occurrence of Predefined Clinically Relevant Disease Associated With RT-PCR-Confirmed RSV-Mediated ARI Over the Whole Study
Description
A participant was considered to have clinically relevant disease with specific parameters associated with an RT-PCR-confirmed RSV-mediated ARI if the following criteria were met: the participant had an RT-PCR-confirmed RSV-mediated ARI: ARI episode initiated by the participant and confirmed by the site with symptoms consistent with an ARI (new symptoms or worsening from baseline of at least one of the symptoms as captured on the RiiQ): sore throat, nasal congestion, cough, short of breath, coughing up phlegm (sputum), wheezing and confirmation of RSV by RT-PCR in one or more of the nasal swabs, or in the sputum sample; any of the following associated with ARI: hospitalization, emergency department visit, per clinical judgement of complications, decreased oxygen saturation, tachypnea, need of supplemental oxygen, hypotension, pulmonary function test and arterial blood gas result.
Time Frame
Baseline (Day 1) up to 24 months
Analysis Population Description
PPE population is defined as population included all randomized and vaccinated participants, excluding those with MPDs expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
16263
8152
Count of Participants | Unit of Measure: Participants
4
11
Secondary Outcome
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
Number of participants with SAEs were reported. An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. 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
28 days post vaccination on Day 1 (Day 29); First year follow-up (from Day 29 up to 6 months, that is, up to Day 154)
Analysis Population Description
Full analysis set (FAS) included all participants with a documented vaccine administration, regardless of the occurrence of protocol deviations. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
16709
8367
Count of Participants | Unit of Measure: Participants
28 days post vaccination on Day 1
119
53
First year follow-up
446
239
Secondary Outcome
Title
Number of Participants With Potential Adverse Events of Special Interest (AESIs)
Description
Number of participants with potential AESIs were reported. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. AESIs were embolic and thrombotic events, hematopoietic thrombocytopenia, and cerebral hemorrhage.
Time Frame
28 days post vaccination on Day 1 (Day 29); First year follow-up (from Day 29 up to 6 months, that is, up to Day 154)
Analysis Population Description
FAS included all participants with a documented vaccine administration, regardless of the occurrence of protocol deviations. Here, 'n' (number analyzed) represents number of participants who were evaluable for specified timepoints.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
16709
8367
Count of Participants | Unit of Measure: Participants
28 days post vaccination on Day 1
25
4
First year follow-up
71
35
Secondary Outcome
Title
Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After Vaccination
Description
Number of participants with solicited local AEs 7 days post vaccination were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. 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 included erythema, swelling, and pain/tenderness at the study vaccine injection site, were used to assess the reactogenicity of the study vaccine and were pre-defined local (injection site). All solicited AEs at the injection site (local) were considered related to the study vaccine administration.
Time Frame
Up to Day 7 post vaccination on Day 1 (up to Day 8)
Analysis Population Description
The safety subset included all participants that consented to the collection of AEs (solicited AEs for up to 7 days after vaccination). Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
2305
1155
Count of Participants | Unit of Measure: Participants
1076
169
Secondary Outcome
Title
Number of Participants With Solicited Systemic AEs up to 7 Days After Vaccination
Description
Number of participants with solicited systemic AEs 7 days post vaccination were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, nausea, pyrexia, 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)
Analysis Population Description
The safety subset (a subset of FAS) included all participants that consented to the collection of AEs (solicited AEs for up to 7 days after vaccination). Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
2305
1155
Count of Participants | Unit of Measure: Participants
1018
236
Secondary Outcome
Title
Number of Participants With Unsolicited AEs up to 28 Days After Vaccination
Description
Number of participants with unsolicited AEs 28 days post vaccination were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant was not specifically questioned in the subject diary.
Time Frame
Up to 28 days post vaccination on Day 1 (up to Day 29)
Analysis Population Description
The safety subset (a subset of FAS) included all participants that consented to the collection of AEs (unsolicited AEs for 28 days after vaccination). Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
2330
1165
Count of Participants | Unit of Measure: Participants
554
206
Secondary Outcome
Title
Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination
Description
RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.
Time Frame
At 14 Days post vaccination on Day 1 (Day 15)
Analysis Population Description
Per-protocol Immunogenicity (PPI) population included all randomized and vaccinated participants who were part of the immunogenicity subset (consisted of at least 360 participants, of whom ~50% were at increased risk for severe RSV disease and ~50% were 75 years or older) and for whom immunogenicity data were available. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
219
108
Geometric Mean (95% Confidence Interval) | Unit of Measure: Titers
7194(6394 - 8093)
537(455 - 634)
Secondary Outcome
Title
Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) Antibodies Immunoglobulin G (IgG) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at 14 Days Post Vaccination
Description
GMTs of preF antibodies IgG at 14 days after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
Time Frame
At 14 days post vaccination on Day 1 (Day 15)
Analysis Population Description
PPI population included all randomized and vaccinated participants who were part of the immunogenicity subset and for whom immunogenicity data were available. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
219
108
Geometric Mean (95% Confidence Interval) | Unit of Measure: Titers
4932(4477 - 5433)
410(348 - 484)
Secondary Outcome
Title
T-cell Interferon (IFN) Gamma Responses to Respiratory Syncytial Virus (RSV) F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)
Description
T-cell IFN gamma responses to RSV F protein specific peptides at 14 days after vaccination as measured by ELISpot assay were reported. RSV F specific T-cell IFN gamma ELISpot responses were measured as counts of spot forming cells per million peripheral blood mononuclear cells (SFC/10^6 PBMCs).
Time Frame
14 days post vaccination on Day 1 (Day 15)
Analysis Population Description
PPI population included all randomized and vaccinated participants who were part of the immuno subset and for whom immunogenicity data were available. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
185
92
Median (Full Range) | Unit of Measure: SFC/10^6 PBMCs
533(306 - 873)
NA(NA - 78)
Secondary Outcome
Title
Area Under the Curve (AUC) of the Change From Baseline in Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Total Symptom Scale Score
Description
RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. The respiratory symptoms included 2 upper respiratory tract infection (URTI) symptoms (nasal congestion and sore throat), 4 lower respiratory tract infection (LRTI) symptoms (cough, wheezing, short of breath, and coughing up phlegm/sputum) and 7 systemic symptoms (headache, feeling feverish, neck pain, body aches and pain, fatigue/tiredness, interrupted sleep, and loss of appetite). Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. RiiQ total Symptom score was the mean of all scores (based on 13 symptoms). The AUC of the change from baseline for the RiiQ total symptom score and the RiiQ lower respiratory symptom score during the ARI was calculated.
Time Frame
Baseline (Day 1) up to 24 months
Analysis Population Description
PPE population includes all randomized and vaccinated participants, excluding those with major protocol deviations (MPDs) expecting to impact the efficacy outcomes. Participants with an RSV onset within 14 days after vaccination and participants who discontinued within 14 days after vaccination were excluded from the PPE population. Here, 'N' (Overall number of participants analyzed) signifies participants who were evaluable for this outcome measure.
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Group 2: Placebo
Overall Number of Participants Analyzed
115
143
Median (Inter-Quartile Range) | Unit of Measure: Scores on a scale*hours
82(21 - 141)
107(48 - 218)
Adverse Events
Time Frame
From Day 1 up to 24 months post-vaccination on Day 1 (Day 731).
Adverse Event Reporting Description
All-cause mortality and serious adverse events (SAEs) were analyzed on Full Analysis Set (FAS) population. Other (not including serious) AEs as solicited and unsolicited AEs were collected and analyzed on a subset of FAS that is called safety subset. The safety subset included all participants that consented to the collection of AEs (solicited and unsolicited AEs).
Arm/Group Title
Group 1: Ad26.RSV.preF and RSV preF Protein
Affected / at Risk (%)
Group 2: Placebo
Affected / at Risk (%)
All-Cause Mortality
Total
105 / 16709 (0.63 %)
61 / 8367 (0.73 %)
Serious Adverse Events
Total
842 / 16709 (5.04 %)
457 / 8367 (5.46 %)
Other (Not Including Serious) Adverse Events
Total
1477 / 2330 (63.39 %)
408 / 1165 (35.02 %)
Limitations and Caveats
Not Specified
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.