A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older (EVERGREEN)

• ClinicalTrials.gov Identifier: NCT04908683
• Recruitment Status: Completed
• First Posted: June 1, 2021
• Results First Posted: February 8, 2024
• Last Update Posted: February 8, 2024
• Sponsor: Janssen Vaccines & Prevention B.V.
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Tracking Information

• First Submitted Date: May 27, 2021
• First Posted Date: June 1, 2021
• Results First Submitted Date: December 21, 2023
• Results First Posted Date: February 8, 2024
• Last Update Posted Date: February 8, 2024
• Actual Study Start Date: July 21, 2021
• Actual Primary Completion Date: July 21, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2023)

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) [ Time Frame: From Baseline (Day 1) up to 12 months ]

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).

Original Primary Outcome Measures (submitted: May 27, 2021)

Percentage of Participants with Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) confirmed Respiratory Syncytial Virus (RSV) mediated Lower Respiratory Tract Disease (LRTD) [ Time Frame: Up to 19 months ]

Percentage of participants with protocol defined RT-PCR confirmed RSV mediated LRTD will be reported.

Current Secondary Outcome Measures (submitted: December 21, 2023)

• Number of Participants With First Occurrence of Any RT-PCR-Confirmed RSV-mediated Acute Respiratory Infection (ARI) [ Time Frame: From Baseline (Day 1) up to 12 months ]
  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).
• Number of Participants With First Occurrence of RT-PCR-Confirmed RSV Mediated LRTD During the Second Year [ Time Frame: From Month 12 up to Month 24 ]
  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).
• Number of Participants With First Occurrence of Any RT-PCR-Confirmed RSV Mediated ARI During the Second Year [ Time Frame: From Month 12 up to Month 24 ]
  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).
• Number of Participants With First Occurrence of Predefined Clinically Relevant Disease Associated With RT-PCR-Confirmed RSV-Mediated ARI Over the Whole Study [ Time Frame: Baseline (Day 1) up to 24 months ]
  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.
• Number of Participants With Serious Adverse Events (SAEs) [ 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) ]
  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.
• Number of Participants With Potential Adverse Events of Special Interest (AESIs) [ 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) ]
  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.
• Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After Vaccination [ Time Frame: Up to Day 7 post vaccination on Day 1 (up to Day 8) ]
  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.
• Number of Participants With Solicited Systemic AEs up to 7 Days After Vaccination [ Time Frame: Up to Day 7 post vaccination on Day 1 (up to Day 8) ]
  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).
• Number of Participants With Unsolicited AEs up to 28 Days After Vaccination [ Time Frame: Up to 28 days post vaccination on Day 1 (up to Day 29) ]
  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.
• Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at 14 Days Post Vaccination [ Time Frame: At 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.
• 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 [ Time Frame: At 14 days post vaccination on Day 1 (Day 15) ]
  GMTs of preF antibodies IgG at 14 days after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
• T-cell Interferon (IFN) Gamma Responses to Respiratory Syncytial Virus (RSV) F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot) [ Time Frame: 14 days post vaccination on Day 1 (Day 15) ]
  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).
• Area Under the Curve (AUC) of the Change From Baseline in Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Total Symptom Scale Score [ Time Frame: Baseline (Day 1) up to 24 months ]
  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.

Original Secondary Outcome Measures (submitted: May 27, 2021)

• Percentage of Participants with RT-PCR Confirmed RSV-mediated Acute Respiratory Infection (ARI) During the First RSV Season [ Time Frame: Up to 9 months ]
  Percentage of participants with RT-PCR confirmed RSV-mediated ARI during the first RSV season will be reported.
• Percentage of Participants with RT-PCR Confirmed RSV-mediated Acute Respiratory Infection (ARI) Over the Whole Study [ Time Frame: Up to 21 months ]
  Percentage of participants with RT-PCR confirmed RSV mediated ARI over the whole study will be reported.
• Percentage of Participants with predefined clinically relevant disease associated with RT-PCR-confirmed RSV-mediated ARI Over the Whole Study [ Time Frame: Up to 21 months ]
  Percentage of participants with predefined clinically relevant disease associated with RT-PCR confirmed RSV mediated ARI over the whole study will be reported.
• Percentage of participants with RT-PCR Confirmed RSV-mediated ARI during the Second RSV Season [ Time Frame: Up to 21 months ]
  Percentage of participants with RT-PCR confirmed RSV-mediated ARI during the second RSV season will be reported.
• Percentage of Participants with RT-PCR Confirmed RSV-mediated LRTD Over the Whole Study [ Time Frame: Up to 21 months ]
  Percentage of participants with RT-PCR confirmed RSV-mediated LRTD over the whole study will be reported.
• Percentage of Participants with RT-PCR Confirmed RSV-mediated Lower Respiratory Tract Disease (LRTD) during the Second RSV Season [ Time Frame: Up to 9 months after Day 365 vaccination (Up to 21 months) ]
  Percentage of participants with RT-PCR confirmed RSV-mediated LRTD during the second RSV season will be reported.
• Percentage of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 21 months ]
  An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
• Percentage of Participants with Adverse Events of Special Interest (AESIs) [ Time Frame: Up to 21 months ]
  Adverse events of special interest that may require expedited reporting or safety evaluation include, but are not limited to: Overdose of a study intervention; suspected abuse/misuse of a study intervention; accidental or occupational exposure to a sponsor study vaccine; Medication error, intercepted medication error, or potential medication error involving a Johnson and Johnson medicinal product (example, product name confusion, product label confusion, intercepted prescribing or dispensing errors).
• Percentage of Participants with Solicited Local Adverse Events (AEs) [ Time Frame: 7 days after each Vaccination (Day 8 and Day 373) ]
  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 are pre-defined local (at the injection site) AEs for which participants will be specifically questioned and which will be noted by participants in their ediary for 7 days post first vaccination (day of vaccination and the subsequent 7 days). Solicited local AEs are: injection site pain/tenderness, erythema and swelling at the vaccination site.
• Percentage of Participants with Solicited Systemic AEs [ Time Frame: 7 days after each Vaccination (Day 8 and Day 373) ]
  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. Participants will be instructed on how to note signs and symptoms in the electronic diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events will include fatigue, headache, nausea, and myalgia.
• Percentage of Participants with Unsolicited AEs [ Time Frame: 28 days after each Vaccination (Day 29 and Day 393) ]
  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 are all AEs for which the participant is not specifically questioned in the participant eDiary.
• RSV Neutralizing Antibody Levels [ Time Frame: Up to 21 months ]
  Analysis of neutralizing antibodies to the RSV A strain will be reported.
• RSV preF and postF Protein Binding Antibodies by Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Up to 21 months ]
  Antibodies binding to RSV F protein in pre-fusion and post-fusion form will be assessed by ELISA.
• Interferon Gamma (IFN-gamma) Enzyme-Linked Immunospot (ELISpot) Assay [ Time Frame: Up to 21 months ]
  RSV F-specific cellular immune responses elicited by the different vaccine regimens.
• Area Under the Curve (AUC) of the Change from Baseline in Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Total Symptom Scale Score [ Time Frame: Baseline up to 21 months ]
  RiiQ is a 4-point scale and it can be scored as a mean of all scores (total symptom scale score) or 2 subscales scores that is respiratory symptoms and systemic symptoms. Respiratory symptoms subscale score is the mean of 6 symptoms, that is, 2 upper respiratory tract infection (URTI) symptoms (nasal congestion and sore throat) and 4 lower respiratory tract infection (LRTI) symptoms (cough, wheezing, shortness of breath, and coughing up phlegm/sputum) whereas systemic symptom subscale score is the mean of 7 systemic symptoms (headache, feeling feverish, neck pain, body aches and pain, fatigue/tiredness, interrupted sleep, and loss of appetite). Each symptom is rated on the scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicating greater severity. The area under the curve during the ARI episode is determined.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older
• Official Title: 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
• Brief Summary: The study will enroll up to 27,200 participants in order to demonstrate the efficacy of the active Ad26.RSV.preF-based study vaccine in the prevention of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed Respiratory Syncytial Virus (RSV)-mediated Lower Respiratory Tract Disease (LRTD) when compared to placebo in adults aged 60 years and above.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Respiratory Syncytial Viruses
• Lower Respiratory Tract Disease

Intervention

• Biological: Adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV). preF
  Participants will receive a single IM injection of an RSV vaccine.
• Biological: Placebo
  Participants will receive a single IM injection of matching placebo.

Study Arms

• Experimental: Group 1: Respiratory Syncytial Virus (RSV) vaccine
  All participants in the active group will receive a single dose intramuscular (IM) injection of study vaccine on Day 1.
  Intervention: Biological: Adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV). preF
• Placebo Comparator: Group 2: Placebo
  All participants in the placebo group will receive a single IM injection of matching placebo on Day 1.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2023): 25236
• Original Estimated Enrollment (submitted: May 27, 2021): 23000
• Actual Study Completion Date: July 21, 2023
• Actual Primary Completion Date: July 21, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must be able to work with smartphones/tablets/computers
• From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood
• Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study
• Before randomization, a participant must be: a. postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and b. not intending to conceive by any methods
• Participants must sign an Inform Consent Form (ICF) indicating that the participant understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study

Exclusion Criteria:

• Has a serious clinically unstable condition, (example, end-stage renal disease with or without dialysis, clinically unstable cardiac disease), Alzheimer's disease, or any other condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise well-being) or that could prevent, confound, or limit the protocol specified assessments
• History of malignancy within 5 years before screening not in the following categories: a. Participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator; b. Participants with a history of malignancy within 5 years, which is considered cured with minimal risk of recurrence per investigator's judgement, can be enrolled
• Had major surgery (example, major cardiopulmonary or abdominal operations) as per the investigator's judgment within 4 weeks before vaccination, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to participate in the study
• Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator, or an employee of the sponsor
• Contraindication to Intramuscular (IM) injections and blood draws (example, bleeding disorders)
• Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, Chile, China, Estonia, Finland, New Zealand, Poland, South Africa, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Colombia, Germany, Japan, Korea, Republic of

Administrative Information

• NCT Number: NCT04908683
• Other Study ID Numbers: CR108959; 2020-005458-97 ( EudraCT Number ); VAC18193RSV3001 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Vaccines & Prevention B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Vaccines & Prevention B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial; Janssen Vaccines & Prevention B.V.

• PRS Account: Janssen Vaccines & Prevention B.V.
• Verification Date: February 2024