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

Healthy Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study for Safety and Immunogenicity Evaluations 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03502707
• Other study ID #: CR108456
• Secondary ID: VAC18193RSV1004
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 6, 2018
• Est. completion date: May 16, 2022

Study information

• Verified date: August 2023
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 669
• Est. completion date: May 16, 2022
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• RSV preF Protein 50 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 50 mcg.
• RSV preF Protein 150 mcg
RSV preF will be administered as a solution for intramuscular injection at a dose of 150 mcg.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Optimal Research	Austin	Texas
United States	Optimal Research	Huntsville	Alabama
United States	Optimal Research	Melbourne	Florida
United States	Optimal Research	Peoria	Illinois
United States	Optimal Research	Rockville	Maryland
United States	Optimal Research	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: 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. The outcome measure was planned to be analyzed for specified arms only.	From Day 1 up to Day 730
Primary	Cohort 2 (Groups 11-13 and 16-18): 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. The outcome measure was planned to be analyzed for specified arms only.	From Day 1 up to Day 730
Primary	Cohort 2 (Groups 14-15): 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. The outcome measure was planned to be analyzed for specified arms only.	From Day 1 up to Day 1095
Primary	Cohort 3: 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. The outcome measure was planned to be analyzed for specified arms only.	From Day 1 up to Day 1095
Primary	Cohort 1: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 1	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 1 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local (injection site) AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post-vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 1 on Day 1 (Day 8)
Primary	Cohort 1: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 2	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 2 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants will be 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).	7 days post-vaccination 2 on Day 57 (Day 64)
Primary	Cohort 1: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 3	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 3 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 3 on Day 365 (Day 372)
Primary	Cohort 2: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 1	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 1 in Cohort 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 1 on Day 1 (Day 8)
Primary	Cohort 2: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 2	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 2 in Cohort 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 2 on Day 57 (Day 64)
Primary	Cohort 3: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 1	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 1 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 1 on Day 1 (Day 8)
Primary	Cohort 3: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 2	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 2 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 2 on Day 365 (Day 372)
Primary	Cohort 3: Number of Participants With Solicited Local (Injection Site) and Systemic AEs at 7 Days Post-vaccination 3	Number of participants with solicited local and systemic AEs at 7 days post-vaccination 3 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site). Systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which will be noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).	7 days post-vaccination 3 on Day 730 (Day 737)
Primary	Cohort 1: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 1	Number of participants with unsolicited AEs post-vaccination 1 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 1 on Day 1 (Day 29)
Primary	Cohort 1: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 2	Number of participants with unsolicited AEs post-vaccination 2 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 2 on Day 57 (Day 85)
Primary	Cohort 1: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 3	Number of participants with unsolicited AEs post-vaccination 3 in Cohort 1 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 3 on Day 365 (Day 393)
Primary	Cohort 2: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 1	Number of participants with unsolicited AEs post-vaccination 1 in Cohort 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 1 on Day 1 (Day 29)
Primary	Cohort 2: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 2	Number of participants with unsolicited AEs post-vaccination 2 in Cohort 2 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 2 on Day 57 (Day 85)
Primary	Cohort 3: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 1	Number of participants with unsolicited AEs post-vaccination 1 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 1 on Day 1 (Day 29)
Primary	Cohort 3: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 2	Number of participants with unsolicited AEs post-vaccination 2 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 2 on Day 365 (Day 393)
Primary	Cohort 3: Number of Participants With Unsolicited AEs at 28 Days Post-vaccination 3	Number of participants with unsolicited AEs post-vaccination 3 in Cohort 3 were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.	28 days post-vaccination 3 on Day 730 (Day 758)
Primary	Cohort 2 (Group 11 to 15): Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers on Day 29	RSV A2 Strain neutralization antibody titers on Day 29 was reported. Geometric mean titers (GMTs) of RSV A2 neutralizing antibodies were measured using the neutralization assay. The outcome measure was planned to be analyzed for specified arms only.	Day 29
Secondary	Cohort 1: RSV A2 Strain Neutralization Antibody Titers at Specified Timepoints	RSV A2 strain neutralization antibody titers at specified timepoints in Cohort 1 was reported. The GMTs of RSV A2 neutralizing antibodies were measured using the neutralization assay.	Days 1, 15, 29, 57, 85, 183, 365, 393, and 547
Secondary	Cohort 3: RSV A2 Strain Neutralization Antibody Titers at Specified Timepoints	RSV A2 strain neutralization antibody titers at specified timepoints in Cohort 3 was reported. The GMTs of RSV A2 neutralizing antibodies were measured using the neutralization assay.	Days 1, 15, 29, 57, 85, 183, 365, 393, 547, 730, 744, 758
Secondary	Cohort 2 (Group 16): RSV A2 Strain Neutralization Antibody Titers on Day 29	RSV A2 strain neutralization antibody titers on Day 29 in Group 16 of Cohort 2 was reported. The GMTs of RSV A2 neutralizing antibodies were measured using the neutralization assay. The outcome measure was planned to be reported for specified arms only.	Day 29
Secondary	Cohort 2 (Group 17): RSV A2 Strain Neutralization Antibody Titers on Day 85	RSV A2 strain neutralization antibody titers on Day 85 in Group 17 of Cohort 2 was reported. The GMTs of RSV A2 neutralizing antibodies were measured using the neutralization assay. The outcome measure was planned to be reported for specified arms only.	Day 85
Secondary	Cohort 1: Pre-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at Specified Timepoints	GMT (ELISA units per liter [EU/L]) of RSV F-protein in pre-fusion form as assessed by ELISA at specified timepoints as assessed by ELISA at specified timepoints in Cohort 1 were reported.	Days 1, 15, 29, 57, 85, 183, 365, 393, and 547
Secondary	Cohort 2: Pre-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at Specified Timepoints	GMT (ELISA units per liter [EU/L]) of RSV F-protein in pre-fusion form as assessed by ELISA at specified timepoints as assessed by ELISA at specified timepoints in Cohort 2 were reported.	Days 1, 15, 29, 57, 85, 183, 365, and 547
Secondary	Cohort 1: Post-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at Specified Timepoints	GMT (EU/L) of RSV F-protein in post-fusion form as assessed by ELISA at specified timepoints for Cohort 1 were reported.	Days 1, 15, 29, 57, 85, 183, 365, 393, and 547
Secondary	Cohort 2: Post-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at Specified Timepoints	GMT (EU/L) of RSV F-protein in post-fusion form as assessed by ELISA at specified timepoints for Cohort 2 were reported.	Days 1, 15, 29, 57, 85, 183, 365, and 547
Secondary	Cohort 1: Breadth of Interferon-gamma (IFN-gamma) T-Cells Responses Against RSV Analyzed by Enzyme-linked Immunospot (ELISpot) Assay at Specified Timepoints	Breadth of IFN-gamma T-Cells responses against RSV analyzed by ELISpot assay at specified timepoints for Cohort 1 were reported. The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. The unit was Spot forming units (SFU)/10^6 peripheral blood mononuclear cells (PBMCs).	Days 1, 15, 29, 57, 85, 183, 365, 393, and 547
Secondary	Cohort 3: Breadth of Interferon-gamma (IFN-gamma) T-Cells Responses Against RSV Analyzed by Enzyme-linked Immunospot (ELISpot) Assay at Specified Timepoints	Breadth of IFN-gamma T-Cells responses against RSV analyzed by ELISpot assay at specified timepoints for Cohort 3 were reported. The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. The unit was SFU/10^6 PBMCs.	Days 1, 15, 29, 57, 85, 183, 365, 393, 730, 744, and 758
Secondary	Cohort 2 (Group 11-16): Breadth of IFN-gamma T-Cells Responses Against RSV Analyzed by ELISpot Assay on Day 29	Breadth of IFN-gamma T-Cells responses against RSV analyzed by ELISpot Assay on Day 29 in Groups 11-16 of Cohort 2 was reported. The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. The outcome measure was planned to be analyzed for specified arms only.	Day 29
Secondary	Cohort 2 (Group 17): Breadth of IFN-gamma T-Cells Responses Analyzed by ELISpot Assay on Day 85	Breadth of IFN-gamma T-Cells responses analyzed by ELISpot assay on Day 85 in Group 17 of Cohort 2 was reported. The ELISPOT assay for F protein-specific gamma interferon-producing T cells was performed using RSV F peptides. The outcome measure was planned to be analyzed for specified arms only.	Day 85