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Respiratory Syncytial VirusesPhase 2CYPRESSNCT03982199

A Study of an Ad26.RSV.preF-based Regimen in the Prevention of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV)-Mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older

A Phase 2 study testing RSV Vaccine in people with Respiratory Syncytial Viruses and Respiratory Tract Diseases, run by Janssen Vaccines & Prevention B.V. at 40 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to demonstrate the efficacy of active study vaccine in the prevention of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed respiratory syncytial virus (RSV)-mediated lower respiratory tract disease (LRTD), when compared to placebo. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
What is being tested?
RSV Vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5,815 participants
Where
40 sitesUnited States
Study dates
1 Aug 2019to 26 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Participant must have a body mass index (BMI) less than (<)40 kilogram per meter square (kg/m^2)
  • Before randomization, a woman 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
  • Participant must be either in good or stable health. Participants may have 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, as long as their symptoms and signs are stable and medically controlled in the judgment of the investigator. Participants will be included on the basis of physical examination, medical history, and vital signs performed between informed consent form (ICF) signature and vaccination on Day 1
  • From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood
  • Participant must be able to read, understand, and complete questionnaires in the eDiary (or a paper safety diary, if designated by the sponsor)
  • Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study

Who cannot join

  • Participant has an acute illness (including acute respiratory illnesses) or body temperature greater than or equal to (>=)38.0 degree Celsius (ºC) within 24 hours prior to administration of study vaccine. In such a situation, enrollment at a later date is permitted
  • Participant has a severe or potentially life-threatening chronic disorder such as severe chronic cardiac diseases and severe chronic lung disease (asthma and COPD), advanced CHF, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer's disease, or has any 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, limit, or confound the protocol-specified assessments
  • Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
  • Per medical history, participant has chronic active hepatitis B or hepatitis C infection
  • Per medical history, participant has human immunodeficiency virus (HIV) type 1 or type 2 infection
  • Participant has a known allergy, or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine)

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

United States40 sites
  • Synexus Clinical Research US Inc

    Akron, Ohio, 44311

  • Anaheim Clinical Trials, LLC

    Anaheim, California, 92801

  • Synexus Clinical Research US Inc

    Aurora, Colorado, 80014

  • Optimal Research

    Austin, Texas, 78705

  • United Medical Associates

    Binghamton, New York, 13901

  • Advanced Clinical Research

    Boise, Idaho, 83642

  • Synexus Clinical Research US Inc

    Chandler, Arizona, 85224

  • Synexus Clinical Research US Inc

    Cincinnati, Ohio, 45236

  • Rapid Medical Research

    Cleveland, Ohio, 44122

  • Lynn Institute

    Colorado Springs, Colorado, 80920

  • Synexus Clinical Research US Inc

    Elkhorn, Nebraska, 68022

  • Regional Clinical Research, Inc.

    Endwell, New York, 13760

  • Synexus Clinical Research US Inc

    Evansville, Indiana, 47714

  • Ventavia Research Group, LLC

    Fort Worth, Texas, 76104

  • Optimal Research

    Huntsville, Alabama, 35802

  • Hutchinson Clinic

    Hutchinson, Kansas, 67502

  • The Center For Pharmaceutical Research

    Kansas City, Missouri, 64114

  • Johnson County Clin-Trials

    Lenexa, Kansas, 66219

  • Optimal Research

    Melbourne, Florida, 32934

  • Coastal Carolina Research Center

    Mt. Pleasant, South Carolina, 29464

  • Synexus Clinical Research US Inc

    Murray, Utah, 84123

  • Heartland Research Associates, LLC

    Newton, Kansas, 67114

  • Lynn Health Science Institute

    Oklahoma City, Oklahoma, 73112

  • Synexus Clinical Research US Inc

    Omaha, Nebraska, 68144

  • Optimal Research

    Peoria, Illinois, 61614

  • Synexus Clinical Research US Inc

    Phoenix, Arizona, 85018

  • Central Phoenix Medical Clinic

    Phoenix, Arizona, 85020

  • Paradigm Clinical Research Centers, Inc.

    Redding, California, 96001

  • Synexus Clinical Research US Inc

    Richfield, Minnesota, 55432

  • University of Rochester / Rochester General Hospital

    Rochester, New York, 14621

  • Optimal Research

    Rockville, Maryland, 20850

  • Benchmark Research

    Sacramento, California, 95684

  • Advanced Clinical Research

    Salt Lake City, Utah, 84123

  • Optimal Research

    San Diego, California, 92108

  • Sundance Clinical Research

    St Louis, Missouri, 63141

  • Synexus Clinical Research US Inc

    St Louis, Missouri, 63141

  • Omega Medical Research

    Warwick, Rhode Island, 02886

  • The Iowa Clinic

    West Des Moines, Iowa, 50266

  • Advanced Clinical Research

    West Jordan, Utah, 84088

  • Heartland Research Associates, LLC

    Wichita, Kansas, 67205

Other trials in United States

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Phase 2b Study to Assess the Efficacy, Immunogenicity and Safety of an Ad26.RSV.preF-based Regimen in the Prevention of RT PCR-confirmed RSV-mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older

The purpose of this study is to demonstrate the efficacy of active study vaccine in the prevention of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed respiratory syncytial virus (RSV)-mediated lower respiratory tract disease (LRTD), when compared to placebo.

Being tested
RSV Vaccine, Placebo
Medical subject headings
Respiratory Tract Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RSV VaccineBiological

    Participants will receive a single IM injection of an Ad26-based RSV vaccine at a single dose level on Day 1 and revaccination after either 1 year, 2 years, or 3 years.

  • PlaceboBiological

    Participants will receive a single IM injection of placebo control on Day 1.

Study groups in NCT03982199
Study groupRoleWhat they receive
Group 1: RSV VaccineExperimentalParticipants will receive a single intramuscular (IM) injection of an adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV) vaccine at a single dose level on Day 1. Participants will then be divided into revaccination subcohorts: 1A, 1B, and 1C to receive revaccination with Ad26.RSV.preF based vaccine at 1 year, 2 years, and 3 years respectively after the first vaccination.
Receives: Biological: RSV Vaccine
Group 2: PlaceboPlacebo comparatorParticipants will receive a single IM injection of placebo control on Day 1. Participants will then be divided into revaccination subcohorts 2A, 2B, and 2C, and will first receive Ad26.RSV.preF based vaccine at years 1, 2, and 3. In subcohorts 2A and 2B, participants will receive a revaccination one year later with either Ad26.RSV.preF based vaccine, study vaccine A or study vaccine B.
Receives: Biological: RSV Vaccine; Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Number of participants with first occurrence of RT-PCR-confirmed RSV mediated LRTD according to case definition-1, 2 and 3 were reported. Case definition 1 was defined as having a new onset or worsening in 3 or more symptoms of lower respiratory tract infection (LRTI) ; Case definition 2 was defined as having a new onset or worsening in greater than or equal to (>=) 2 symptoms of LRTI; and Case definition 3 was defined as having a new onset or worsening in >=2 OR >=1 symptoms of LRTI with >=1 systemic symptoms. Systemic symptoms (fatigue/malaise and fever/feverishness) and symptoms of LRTI (cough, shortness of breath, sputum production, wheezing and tachypnea) were collected via the RiiQ. 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 LRTD symptom scores.

    Measured: From screening (Day 1) up to 9 months

Secondary outcomes (16)
  1. Main Cohorts: Number of Participants With Any RT-PCR-confirmed RSV Disease

    Number of participants with any RT-PCR-confirmed RSV disease were reported. The analysis was based on poisson regression model.

    Measured: From screening (Day 1) up to 9 months

  2. Main Cohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers

    RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.

    Measured: Days 15, 85, 169, 365

  3. Revaccination Subcohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers

    RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.

    Measured: Days 15, 365, 379, 393, 449, 730, 737, 744, 758

  4. Revaccination Subcohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

    GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.

    Measured: Day 15: Arms 3 to 7,13 and 14; Days 365, 379, 393, 449, 533: Arms 3 to 7; Day 730: Arms 4 to 7; Days 737, 744, 758: Arms 5 to 7; Day 1095, 1109: Arms 13 and 14

  5. Revaccination Subcohort 2A: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)

    T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein 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).

    Measured: Days 730, 744, 758

  6. Main Cohorts: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)

    T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein 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).

    Measured: Days 15, 85, 169, 365, 533

  7. Main Cohorts: Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After First Vaccination

    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/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.

    Measured: Up to Day 8 (7 days after first vaccination on Day 1)

  8. Main Cohorts: Number of Participants With Solicited Systemic AEs up to 7 Days After First Vaccination

    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, arthralgia, and fever (defined as an endogenous elevation of body temperature >=38.0°C, as recorded in at least one measurement).

    Measured: Up to Day 8 (7 days after first vaccination on Day 1)

  9. Main Cohorts: Number of Participants With Unsolicited AEs up to 28 Days After First Vaccination

    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 is not specifically questioned in the participant diary.

    Measured: Up to Day 29 (28 days after first vaccination on Day 1)

  10. Revaccination Subcohorts: Number of Participants With Solicited Local AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years

    Number of participants with solicited local AEs 7 days after re-vaccination at 1, 2 and 3 years 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/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.

    Measured: Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102)

  11. Revaccination Subcohorts: Number of Participants With Solicited Systemic AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years

    Number of participants with solicited systemic AEs 7 days after re-vaccination up to 1, 2 and 3 years 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, arthralgia, and fever (defined as an endogenous elevation of body temperature >=38.0°C, as recorded in at least one measurement).

    Measured: Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102)

  12. Revaccination Subcohorts: Number of Participants With Unsolicited AEs 28 Days After Re-vaccination up to 1, 2 and 3 Years

    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 is not specifically questioned in the participant diary.

    Measured: Arms 3,4: 28 days after revacc at 1 year (up to Day 393); Arms 5,6,7,8,9: 28 days after revacc at 2 years (up to Day 758); Arms 10,11,12,13,14: 28 days after revaccination at 3 year (up to Day 1123)

  13. Revaccination Subcohorts: Number of Participants With Adverse Events of Special Interests (AESI)

    Number of participants with AESIs were reported. An AE was 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.

    Measured: Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277)

  14. Main Cohorts:Number of Participants With Serious Adverse Events (SAEs)

    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 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/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. For participants who were not revaccinated only SAEs associated with ARIs and complications related to ARIs that classify as SAEs, SAEs classified as related, SAEs resulting in death, and (S)AEs resulting in study discontinuation or from procedures and non-investigational (concomitant) Janssen products were collected.

    Measured: From Day 1 up to Day 1095

  15. Revaccination Subcohorts: Number of Participants With Serious Adverse Events (SAEs)

    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 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/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measured: Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277)

  16. Main Cohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

    GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.

    Measured: Days 15, 85, 169, 365, 533

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2019
  2. Study start1 Aug 2019
  3. Primary completion6 Jun 2022
  4. Study completion26 May 2023

Why it stopped: The study was terminated early by the sponsor due to strategic reprioritization reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
5,815 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03982199
Sponsor's protocol ID
CR108634
Other IDs
VAC18193RSV2001
Acronym
CYPRESS
Status last verified
May 2025
First submitted
10 Jun 2019
Last updated
25 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Falsey AR, Hosman T, Bastian AR, Vandenberghe S, Chan EKH, Douoguih M, Heijnen E, Comeaux CA, Callendret B; CYPRESS investigators. Long-term efficacy and immunogenicity of Ad26.RSV.preF-RSV preF protein vaccine (CYPRESS): a randomised, double-blind, placebo-controlled, phase 2b study. Lancet Infect Dis. 2024 Sep;24(9):1015-1024. doi: 10.1016/S1473-3099(24)00226-3. Epub 2024 May 24.

    PubMed 38801826
  • Falsey AR, Williams K, Gymnopoulou E, Bart S, Ervin J, Bastian AR, Menten J, De Paepe E, Vandenberghe S, Chan EKH, Sadoff J, Douoguih M, Callendret B, Comeaux CA, Heijnen E; CYPRESS Investigators. Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults. N Engl J Med. 2023 Feb 16;388(7):609-620. doi: 10.1056/NEJMoa2207566.

    PubMed 36791161

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RSV Vaccine in people with Respiratory Syncytial Viruses and Respiratory Tract Diseases, run by Janssen Vaccines & Prevention B.V. at 40 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 screening (Day 1) up to 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03982199, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.

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