A Phase 3, Observer-blind, Randomized, Placebo-controlled Study to Evaluate the Non-inferiority of the Immune Response and Safety of the RSVPreF3 OA Investigational Vaccine in Adults 50-59 Years of Age, Including Adults at Increased Risk of Respiratory Syncytial Virus Lower Respiratory Tract Disease, Compared to Older Adults ≥60 Years of Age
Overview
- Phase
- Phase 3
- Intervention
- RSVPreF3 OA investigational vaccine
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1544
- Primary Endpoint
- RSV-A Neutralization Titers Expressed as Group Geometric Mean Titer (GMT) in Healthy Participants Compared to OA-RSV Group
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The aim of this study is to demonstrate the non-inferiority (NI) of the immune response and evaluate safety of RSVPreF3 older adults (OA) investigational vaccine in adults 50-59 years of age (YOA), including those who are at increased risk (AIR) of respiratory syncytial virus (RSV)-lower respiratory tract disease (LRTD), versus adults >=60 YOA
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol
- •Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.
- •Specific inclusion criteria for all participants in Cohort 1 (Adults HA-RSV Group, Adults HA-Placebo Group, Adults AIR-RSV Group \& Adults AIR-Placebo Group)
- •A male or female participant 50-59 YOA at the time of the study intervention administration.
- •Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy or post-menopause.
- •Female participants of childbearing potential may be enrolled in the study, if the participant:
- •has practiced adequate contraception from 1 month prior to study intervention administration until study end for this study, and
- •has a negative pregnancy test on the day of study intervention administration.
- •Specific inclusion criteria for participants in the Adults-HA Sub-cohort
- •Healthy participants as established by medical history and clinical examination before entering into the study.
Exclusion Criteria
- •Medical conditions
- •Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination (no laboratory testing required).
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
- •Hypersensitivity to latex.
- •Unstable chronic illness.
- •Any history of dementia or any medical condition that moderately or severely impairs cognition.
- •Recurrent or uncontrolled neurological disorders or seizures. Participants with medically controlled active or chronic neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol. Study participants may decide to assign a caregiver to help them complete the study procedures.
- •Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study.
- •Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
- •Prior/Concomitant therapy
Arms & Interventions
Adults HA-RSV Group
Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-Lower respiratory tract disease (RSV-LRTD), aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.
Intervention: RSVPreF3 OA investigational vaccine
Adults HA-Placebo Group
Healthy adults or adults with chronic stable conditions with or without treatment that do not lead to an increased risk of RSV-LRTD, aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end.
Intervention: Placebo
Adults AIR-RSV Group
Adults at increased risk of RSV-Lower respiratory tract disease (RSV-LRTD) aged 50-59 years old received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.
Intervention: RSVPreF3 OA investigational vaccine
Adults AIR-Placebo Group
Adults at increased risk of RSV-LRTD aged 50-59 years old received 1 dose of placebo at Day 1 and were followed until study end.
Intervention: Placebo
OA-RSV Group
Older adults aged 60 years old and above received 1 dose of RSVPreF3 OA vaccine at Day 1 and were followed until study end.
Intervention: RSVPreF3 OA investigational vaccine
Outcomes
Primary Outcomes
RSV-A Neutralization Titers Expressed as Group Geometric Mean Titer (GMT) in Healthy Participants Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Serological assays for the determination of antibodies against RSV-A were performed by neutralization assay. The corresponding antibody titers were expressed in Estimated Dilution 60 (ED60) and were measured on blood samples collected from vaccinated subjects. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
RSV-A Neutralization Titers Expressed as Group Seroresponse Rate (SRR) Difference in Healthy Participants Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) greater than or equal to 4 (\>=4).
RSV-B Neutralization Titers Expressed as Group GMT in Healthy Participants Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Serological assays for the determination of antibodies against RSV-B were performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult HA-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
RSV-B Neutralization Titers Expressed as Group SRR in Healthy Participants Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
RSV-A Neutralization Titers Expressed as Group GMT Titer in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-A neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
RSV-A Neutralization Titers Expressed as Group SRR in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
RSV-B Neutralization Titers Expressed as Group GMT in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. The ANCOVA model used to calculate the adjusted GMTs for RSV-B neutralizing antibodies included the baseline value as covariate (i.e. GMTs are adjusted for the PRE timepoint values) and only included Adult AIR-RSV and OA-RSV groups in the model as fixed effect, as specified in Statistical Analysis Plan.
RSV-B Neutralization Titers Expressed as Group SRR in Participants at Increased Risk of RSV-LRTD (Adults-AIR-RSV Group) Compared to OA-RSV Group
Time Frame: At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)
The SRR is defined as the proportion of participants having a fold increase in neutralization titers (1 month post-study intervention administration over pre-study intervention administration) \>=4.
Secondary Outcomes
- Percentage of Participants Reporting Each Solicited Administration Site Event (Pain, Redness and Swelling)(During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting Each Solicited Systemic Event (Fever, Headache, Muscle Pain, Joint Pain, Tiredness)(During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting Any Unsolicited Adverse Events (AEs)(During the 30-day follow up period after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting Any Serious Adverse Events (SAEs) Within 6 Months of Vaccination(From the day of the vaccination up to 6 months after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting Any Onset Potential Immune Mediated Diseases (pIMDs) Within 6 Months of Vaccination(From the day of the vaccination up to 6 months after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting SAEs Related to Study Intervention Administration Within 12 Months of Vaccination(From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting pIMDs Related to Study Intervention Administration Within 12 Months of Vaccination(From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1))
- Percentage of Participants Reporting Any Fatal SAEs(From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1))
- RSV-A Neutralization Titers Expressed as GMT, up to One Month Post-intervention(At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31))
- RSV-A Neutralization Titers Expressed as GMT at Month 6 and Month 12 Post-intervention(At 6 months and at 12 months after study intervention administration)
- RSV-B Neutralization Titers Expressed as GMT, up to One Month Post-intervention(At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31))
- RSV-B Neutralization Titers Expressed as GMT, at Month 6 and Month 12 Post-intervention(At 6 months and at 12 months after study intervention administration)
- Frequency of RSVPreF3-specific Cluster of Differentiation (CD)4+ T Cells Expressing at Least 2 Activation Markers up to One Month Post-intervention(At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31))
- Frequency of RSVPreF3-specific CD4+ T Cells Expressing at Least 2 Activation Markers, at Month 6 and Month 12 Post-intervention(At 6 months and at 12 months after study intervention administration)
- Frequency of RSVPreF3-specific CD8+ T Cells Expressing at Least 2 Activation Markers, up to One Month Post-intervention(At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31))
- Frequency of RSVPreF3-specific CD8+ T Cells Expressing at Least 2 Activation Markers, at Month 6 and Month 12(At 6 months and at 12 months after study intervention administration)