A Study to Evaluate the Safety and Immunogenicity for Regimen Selection of Ad26.RSV.preF and/or RSV preF Protein Combinations Followed by Expanded Safety Evaluation in Adults Aged 60 Years and Older
Study Details
Study Description
Brief Summary
The purpose of this study for:
Cohort 1 and Cohort 2: to assess the safety and reactogenicity of the intramuscular one- and two-dose regimens, with a booster at Month 12 (Cohort 1) and to select a regimen for Cohort 3.
Cohort 2 and part of Cohort 1: to assess respiratory syncytial virus (RSV) neutralizing antibody levels of the regimens containing RSV pre-fusion (preF) protein compared to the one-dose adenovirus serotype 26 respiratory syncytial virus pre-fusion (Ad26.RSV.preF) regimen.
Cohort 3: to assess the safety and reactogenicity of the selected regimen and a booster at Month 12 and/or Month 24.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Cohort (C)1 Group (G)1: Placebo for RSV preF Protein Participants will receive intramuscular injection of placebo on Day 1, Day 57 and at Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
| Experimental: C1 G2: RSV preF Protein Participants will receive intramuscular injection of 50 microgram (mcg) RSV preF protein on Day 1, Day 57 and at Month 12. |
Biological: RSV preF Protein 50 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 50 mcg.
Other Names:
|
| Placebo Comparator: C1 G3: Placebo for Ad26.RSV.preF/RSV preF or RSV preF Protein Participants will receive intramuscular injection of placebo on Day 1, Day 57 and at Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
| Experimental: C1 G4: Mixture of Ad26.RSV.preF/RSV preF Protein Participants will receive intramuscular injection of a mixture of 5*10^10 viral particles (vp) of Ad26.RSV.preF/RSV preF 50 mcg protein on Day 1, Day 57 and at Month 12. |
Biological: Mixture of Ad26.RSV.preF 5*10^10 vp Plus RSV preF Protein 50 mcg
Mixture of Ad26.RSV.preF (5*10^10 vp) and RSV preF protein (50 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C1 G5: RSV preF Protein Participants will receive intramuscular injection of 150 mcg RSV preF protein on Day 1, Day 57 and at Month 12. |
Biological: RSV preF Protein 150 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 150 mcg.
Other Names:
|
| Placebo Comparator: C1 G6: Mixture of Placebo for Ad26.RSV.preF/RSV preF Protein Participants will receive intramuscular injection of placebo on Day 1, Day 57 and at Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
| Experimental: C1 G7: Mixture of Ad26.RSV.preF/RSV preF Protein Participants will receive intramuscular injection of a mixture of 5*10^10 vp of Ad26.RSV.preF plus 150 mcg RSV preF protein on Day 1, Day 57 and at Month 12. |
Biological: Mixture of Ad26.RSV.preF 5*10^10 vp Plus RSV preF Protein 150 mcg
Mixture of Ad26.RSV.preF (5*10^10 vp) and RSV preF protein (150 mcg) will be administered as a solution for intramuscular injection.
|
| Placebo Comparator: C1 G8: Placebo for Ad26.RSV.preF/Placebo for RSV preF Protein Participants will receive intramuscular injection of placebo on Day 1 and at Month 12 and in only 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
| Experimental: C1 G9: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Participants will receive intramuscular injection of a mixture of 1*10^11 vp of Ad26.RSV.preF plus 150 mcg RSV preF protein in 1 arm on Day 1 and 57 and at Month 12 and placebo in another arm on Day 1 and at Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 1*10^11 vp Plus RSV preF Protein 150 mcg
Mixture of Ad26.RSV.preF (1*10^11 vp) and RSV preF protein (150 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C1 G10: Ad26.RSV.preF, RSV preF Protein and Placebo Participants will receive separate intramuscular injections of 1*10^11 vp of Ad26.RSV.preF in 1 Arm and 150 mcg RSV preF protein in another arm on Day 1 and at Month 12 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: RSV preF Protein 150 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 150 mcg.
Other Names:
Biological: Ad26.RSV.preF 1*10^11 vp
Ad26.RSV.preF will be administered as a solution for intramuscular injection at a dose of 1*10^11 vp.
Other Names:
|
| Experimental: C2 G11: Ad26.RSV.preF and Placebo Participants will receive intramuscular injection of 1*10^11 vp of Ad26.RSV.preF in 1 arm and placebo in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Ad26.RSV.preF 1*10^11 vp
Ad26.RSV.preF will be administered as a solution for intramuscular injection at a dose of 1*10^11 vp.
Other Names:
|
| Experimental: C2 G12: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Participants will receive intramuscular injection of a mixture of 5*10^10 vp Ad26.RSV.preF plus 50 mcg RSV preF protein in 1 arm and placebo in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 5*10^10 vp Plus RSV preF Protein 50 mcg
Mixture of Ad26.RSV.preF (5*10^10 vp) and RSV preF protein (50 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C2 G13: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Participants will receive intramuscular injection of a mixture of 1*10^11 vp Ad26.RSV.preF plus 50 mcg RSV preF protein in 1 arm and placebo in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 1*10^11 vp Plus RSV preF Protein 50 mcg
Mixture of Ad26.RSV.preF (1*10^11 vp) and RSV preF protein (50 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C2 G14: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Participants will receive intramuscular injection of a mixture of 1*10^11 vp Ad26.RSV.preF plus 150 mcg RSV preF protein in 1 arm and placebo in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 1*10^11 vp Plus RSV preF Protein 150 mcg
Mixture of Ad26.RSV.preF (1*10^11 vp) and RSV preF protein (150 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C2 G15: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Participants will receive intramuscular injection of a mixture of 5*10^10 vp Ad26.RSV.preF plus 150 mcg RSV preF protein in 1 arm and placebo in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 5*10^10 vp Plus RSV preF Protein 150 mcg
Mixture of Ad26.RSV.preF (5*10^10 vp) and RSV preF protein (150 mcg) will be administered as a solution for intramuscular injection.
|
| Experimental: C2 G16: Ad26.RSV.preF, RSV preF Protein and Placebo Data from C1 G10 will be pooled with those of C2 G16. Participants will receive separate intramuscular injections of 1*10^11 vp of Ad26.RSV.preF in 1 Arm and 150 mcg RSV preF protein in another arm on Day 1 and placebo in 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: RSV preF Protein 150 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 150 mcg.
Other Names:
Biological: Ad26.RSV.preF 1*10^11 vp
Ad26.RSV.preF will be administered as a solution for intramuscular injection at a dose of 1*10^11 vp.
Other Names:
|
| Experimental: C2 G17: Mixture of Ad26.RSV.preF/RSV preF Protein and Placebo Data from C1 G9 will be pooled with those of C2 G17. Participants will receive intramuscular injection of a mixture of 1*10^11 vp of Ad26.RSV.preF plus 150 mcg RSV preF protein in 1 arm on Day 1 and 57 and placebo in another arm on Day 1. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Mixture of Ad26.RSV.preF 1*10^11 vp Plus RSV preF Protein 150 mcg
Mixture of Ad26.RSV.preF (1*10^11 vp) and RSV preF protein (150 mcg) will be administered as a solution for intramuscular injection.
|
| Placebo Comparator: C2 G18: Placebo for Ad26.RSV.preF/Placebo for RSV preF Protein Participants will receive intramuscular injection of placebo in separate arms on Day 1 and in only 1 arm on Day 57. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
| Experimental: C3 G19: Selected Regimen (SR) If a one-dose regimen is selected, participants in this group will receive SR on Day 1 and a booster (the SR) at Month 12 and month 24. The participants who are randomized to two-dose regimen will receive SR on Day 1 and Day 57, and a booster (the selected regimen) at Month 12. |
Biological: Selected Regimen
A regimen from Cohort 1 or Cohort 2 will be selected and administered as a solution for intramuscular injection at the selected dose.
|
| Experimental: C3 G20: SR + Placebo for SR If a one-dose regimen is selected, participants in this group will receive SR on Day 1 and Month 24, and a placebo at Month 12. The participants who are randomized to two-dose regimen will receive selected regimen on Day 1 and Day 57, and a placebo at Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
Biological: Selected Regimen
A regimen from Cohort 1 or Cohort 2 will be selected and administered as a solution for intramuscular injection at the selected dose.
|
| Placebo Comparator: C3 G21: Placebo for SR If a one-dose regimen is selected, participants in this group will receive placebo for SR on Day 1 and at Month 12 and Month 24. The participants who are randomized to two-dose regimen will receive placebo for SR on Day 1, Day 57, and Month 12. |
Biological: Placebo
Placebo for Ad26.RSV.preF, RSV preF protein, Ad26.RSV.preF/RSV preF protein mixture and selected regimen will be administered as sterile saline for intramuscular injection.
|
Outcome Measures
Primary Outcome Measures
- Cohorts 1, 2, and 3: Number of Participants With Serious Adverse Events (SAEs) [From Day 1 until the End of Study (up to maximum of 3 years)]
An SAE is an adverse event (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.
- Cohorts 1, 2, and 3: Number of Participants With Solicited Local and Systemic AEs for 7 Days After Each Vaccination [From Day 1 until 7 days after each vaccination (up to maximum of Day 737)]
Solicited AEs are pre-defined local (at the injection site) and systemic events for which participants are specifically questioned and which are noted by participants in their diary. Solicited local AEs: pain/tenderness, induration/swelling and erythema. Solicited systemic AEs: fever, fatigue, headache, myalgia, arthralgia, chills, and nausea. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
- Cohorts 1, 2, and 3: Number of Participants With Unsolicited AEs for 28 Days After Each Vaccination [From Day 1 until 28 days after each vaccination (up to maximum of Day 758)]
Unsolicited AEs are all AEs for which participants are specifically not questioned in the participant diary. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
- Cohort 2: Respiratory Syncytial Virus (RSV) A2 Neutralizing Antibody Levels [Day 29 (for 1-dose regimen)]
Analysis of RSV A2 neutralizing antibody levels of the vaccine-induced immune response.
Secondary Outcome Measures
- Cohort 1: Respiratory Syncytial Virus (RSV) Neutralization Assays [At Day 1 (1st vaccination), Day 15, 29, 57 (2nd vaccination), Day 85, 183, 365 (3rd vaccination), Day 393, 547, 730 or Early Exit (up to 2 years)]
Analysis of neutralizing antibodies to RSV will be performed.
- Cohorts 1 and 2: RSV Fusion Protein (F Protein) Binding Antibodies (Enzyme-Linked Immunosorbent Assay [ELISA]; Pre-Fusion [Pre-F] and/or Post-Fusion [Post-F]) [At Day 1 (1st vaccination), Day 15, 29, 57 (2nd vaccination), Day 85, 183, 365, Day 393 (Cohort 1 only), Day 547, 730 or Early Exit (up to 2 years)]
Analysis of antibodies binding to RSV F protein in post-fusion (stable conformation) and pre-fusion (metastable conformation) form will be performed.
- Cohorts 1 and 2: Interferon Gamma (IFN-γ) Enzyme-Linked Immunospot (ELISpot) Assay [At Day 1 (1st vaccination), Day 15, 29, 57 (2nd vaccination), Day 85, 183, 365, Day 393 (Cohort 1 only), Day 547, 730 or Early Exit (up to 2 years)]
IFN-γ ELISpot assay to assess the RSV F-specific cellular immune responses elicited by the different vaccine regimens.
- Cohort 1 and 2: RSV A2 Neutralizing Antibody Levels [At Day 1 (1st vaccination), Day 15, 29, 57 (2nd vaccination), Day 85, 183, 365, Day 393 (Cohort 1 only), Day 547, 730 or Early Exit (up to 2 years)]
Analysis of RSV A2 neutralizing antibody levels of the vaccine-induced immune response.
- Cohort 3: RSV Neutralization A2 Strain [Day 29 (for 1-dose regimen) and Day 85 (for 2-dose regimen)]
Analysis of RSV A2 neutralizing antibody titers of the vaccine-induced immune response.
- Cohort 3: IFN-γ ELISpot Assay [Day 29 (for 1-dose regimen) and Day 85 (for 2-dose regimen)]
IFN-γ ELISpot assay to assess the RSV F-specific cellular immune responses elicited by the selected vaccine regimen.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
-
In the investigator's clinical judgment, participant must be either in good or stable health. Participants may have underlying illnesses such as hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are medically controlled. If they are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
-
For participants in Cohorts 1 and 2 only: Participant must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the laboratory screening tests are outside the central laboratory normal reference ranges and additionally within the limits of toxicity Grade 2 according to the United States (US) Food and Drug Administration (FDA) toxicity, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant and appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
-
From the time of each vaccination through 3 months after each vaccination, participant agrees not to donate blood
-
Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study
Exclusion Criteria:
-
Per serology testing in Cohorts 1 and 2 and per medical history in Cohort 3: Participant has chronic active hepatitis B or hepatitis C infection, documented by hepatitis B surface antigen and hepatitis C antibody, respectively
-
Per serology testing in Cohorts 1 and 2 and per medical history in Cohort 3: Participant has human immunodeficiency virus (HIV) type 1 or type 2 infection
-
Participant has had major psychiatric illness and/or drug or alcohol abuse which in the investigator's opinion would compromise the participant's safety and/or compliance with the study procedures
-
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)
-
Participant has received respiratory syncytial virus (RSV) vaccine in a previous RSV vaccine study at any time prior to randomization
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Optimal Research | Huntsville | Alabama | United States | 35802 |
| 2 | Optimal Research | San Diego | California | United States | 92108 |
| 3 | Optimal Research | Melbourne | Florida | United States | 32934 |
| 4 | Optimal Research | Peoria | Illinois | United States | 61614 |
| 5 | Optimal Research | Rockville | Maryland | United States | 20850 |
| 6 | Optimal Research | Austin | Texas | United States | 78705 |
Sponsors and Collaborators
- Janssen Vaccines & Prevention B.V.
Investigators
- Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial, Janssen Vaccines & Prevention B.V.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108456
- VAC18193RSV1004