A Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus Given to 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 and Above

Respiratory Syncytial Virus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05590403
• Other study ID #: 219238
• Secondary ID: 2022-001981-36
• Status: Completed
• Phase: Phase 3
• Start date: October 28, 2022
• Est. completion date: April 3, 2024

Study information

• Verified date: April 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1544
• Est. completion date: April 3, 2024
• Est. primary completion date: March 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

1. 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.

• Participants with chronic stable medical conditions with or without specific treatment, such as hypertension, hypercholesterolemia, or hypothyroidism, and who are not at increased risk for RSV-LRTD , are allowed to participate in this study if considered by the investigator as medically stable (no changes in the treatment or disease severity in the past 3 months).

Specific inclusion criteria for participants in the Adults-AIR Sub cohort

Participants should be diagnosed with at least 1 of the following medical conditions and have a stable condition (no changes in the treatment or disease severity in the past 3 months):

• Chronic pulmonary disease resulting in activity restricting symptoms or use of long-term medication

• Chronic cardiovascular disease

• Diabetes mellitus: types 1 and 2

• Other diseases at increased risk for RSV-LRTD disease

• Chronic kidney disease

• Chronic liver disease 2. Specific inclusion criteria for Cohort 2 (OA-RSV Group)

• A male or female participant =60 YOA at the time of the study intervention administration.

• Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease are allowed to participate in this study if considered by the investigator as medically stable (no changes in the treatment or disease severity in the past 3 months).

• Participants living in the general community or in an assisted-living facility that provides minimal assistance, such that the participant is primarily responsible for self-care and activities of daily living.

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

• Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study intervention during the period beginning 30 days before the dose of study intervention (Day -29 to Day 1), or planned use during the study period (up to Visit 4, Month 12).

• Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after the dose of study intervention administration, with the exception of inactivated and subunit influenza vaccines or COVID-19 vaccines (fully licensed or with EUA) which can be administered up to 14 days before or from 14 days after the study intervention administration.

Note: In case an emergency mass vaccination for an unforeseen public health threat is recommended and/or organized by the public health authorities, outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

• Previous vaccination with an RSV vaccine, including investigational RSV vaccines.

• Chronic administration of immune-modifying drugs (defined as more than 14 consecutive days in total) and/or administration of long-acting immune modifying treatments or planned administration at any time up to the end of the study.

• Up to 3 months prior to the study intervention administration:

• For corticosteroids, this will mean prednisone =20 mg/day, or equivalent. Inhaled and topical steroids are allowed.

• Administration of immunoglobulins and/or any blood products or plasma derivatives.

• Up to 6 months prior to study intervention administration: long-acting immune modifying drugs including among others immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or invasive medical device).

Other exclusions Other exclusions for all participants

• History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures.

• Bedridden participants.

• Planned move during the study period that will prohibit participating in the study until study end.

• Participation of any study personnel or their immediate dependents, family, or household members.

Other exclusions for Cohort 1

• Pregnant or lactating female.

• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections
• Respiratory Tract Diseases

Intervention

Biological:
• RSVPreF3 OA investigational vaccine
One dose administered intramuscularly at Day 1.

Drug:
• Placebo
One dose administered intramuscularly at Day 1.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Caba	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad de Buenos Aires
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	New Westminster	British Columbia
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	St-Charles-Borromée	Quebec
Canada	GSK Investigational Site	Trois-Rivieres	Quebec
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Victoria	British Columbia
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Stuhr	Niedersachsen
Germany	GSK Investigational Site	Wallerfing	Bayern
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wuerzburg	Bayern
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Zwijndrecht
Poland	GSK Investigational Site	Elblag
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Piaseczno
Poland	GSK Investigational Site	Wroclaw
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Hospitalet de Llobregat
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pama de Mallorca
Spain	GSK Investigational Site	Pozuelo De Alarcón	Madrid
Spain	GSK Investigational Site	Vigo
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Daphne	Alabama
United States	GSK Investigational Site	Fort Myers	Florida
United States	GSK Investigational Site	Immokalee	Florida
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Mishawaka	Indiana
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Waterbury	Connecticut
United States	GSK Investigational Site	Wenatchee	Washington
United States	GSK Investigational Site	Wichita	Kansas
United States	GSK Investigational Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Germany,  Japan,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RSV-A Neutralization Titers Expressed as Group Geometric Mean Titer (GMT) in Healthy Participants Compared to OA-RSV Group	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.	At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Primary	RSV-A Neutralization Titers Expressed as Group Seroresponse Rate (SRR) Difference in Healthy Participants Compared to OA-RSV Group	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).	At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)
Primary	RSV-B Neutralization Titers Expressed as Group GMT in Healthy Participants Compared to OA-RSV Group	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.	At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Primary	RSV-B Neutralization Titers Expressed as Group SRR in Healthy Participants Compared to OA-RSV Group	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.	At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)
Primary	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	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.	At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)
Primary	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	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.	At 1 month after the RSVPreF3 OA vaccine administration (Day 31) compared to baseline (Day 1)
Primary	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	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.	At 1 month after the RSVPreF3 OA vaccine administration (Day 31)
Primary	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	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.	At 1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)
Secondary	Percentage of Participants Reporting Each Solicited Administration Site Event (Pain, Redness and Swelling)	Assessed solicited administration site events were pain, erythema and swelling. Any = occurrence of the symptom regardless of intensity grade. Any erythema and swelling symptom = symptom reported with a surface diameter greater than 0 millimeters.	During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1)
Secondary	Percentage of Participants Reporting Each Solicited Systemic Event (Fever, Headache, Muscle Pain, Joint Pain, Tiredness)	Assessed solicited systemic events were arthralgia, fatigue, headache, myalgia and fever [temperature equal to or above (>=) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relation to study intervention.	During the 4-day follow up period after vaccination (vaccine or placebo administered on Day 1)
Secondary	Percentage of Participants Reporting Any Unsolicited Adverse Events (AEs)	Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.	During the 30-day follow up period after vaccination (vaccine or placebo administered on Day 1)
Secondary	Percentage of Participants Reporting Any Serious Adverse Events (SAEs)	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or results in an abnormal pregnancy outcome.	From the day of the vaccination (Day 1) up to 6 months post dose (Month 6)
Secondary	Percentage of Participants Reporting Any Potential Immune Mediated Diseases (pIMDs)	pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.	From the day of the vaccination (Day 1) up to 6 months post dose (Month 6)
Secondary	Percentage of Participants Reporting SAEs Related to Study Intervention Administration	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or results in an abnormal pregnancy outcome.	From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1)
Secondary	Percentage of Participants Reporting pIMDs Related to Study Intervention Administration	pIMDs are a subset of AEs of special interest that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.	From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1)
Secondary	Percentage of Participants Reporting Any Fatal SAEs	An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, or results in an abnormal pregnancy outcome.	From the day of the vaccination up to 12 months after vaccination (vaccine or placebo administered on Day 1)
Secondary	RSV-A Neutralization Titers Expressed as GMT, up to One Month Post-intervention	Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. Unadjusted GMTs were provided for Adult HA_RSV, Adults HA-Placebo, Adult AIR_RSV, Adult AIR_Placebo and OA_RSV groups.	At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31)
Secondary	RSV-A Neutralization Titers Expressed as GMT at Month 6 and Month 12 Post-intervention	Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay. The corresponding antibody titers were expressed in ED60.	At 6 months and at 12 months after study intervention administration
Secondary	RSV-B Neutralization Titers Expressed as GMT, up to One Month Post-intervention	Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60. Unadjusted GMTs were provided for Adult HA_RSV, Adults HA-Placebo, Adult AIR_RSV, Adult AIR_Placebo and OA_RSV groups.	At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31)
Secondary	RSV-B Neutralization Titers Expressed as GMT, at Month 6 and Month 12 Post-intervention	Serological assays for the determination of antibodies against RSV-B are performed by neutralization assay. The corresponding antibody titers were expressed in ED60.	At 6 months and at 12 months after study intervention administration
Secondary	Frequency of RSVPreF3-specific Cluster of Differentiation (CD)4+ T Cells Expressing at Least 2 Activation Markers up to One Month Post-intervention	Among markers expressed are interleukin-2/13/17 (IL-2, IL-13, IL-17), cluster of 40 ligand (CD40L), 41BB, tumour necrosis factor alpha (TNF-a) and interferon gamma (IFN-?), in vitro upon stimulation with RSVPreF3 peptide preparations.	At pre-study intervention administration (Day 1) and 1 months after study intervention administration (Day 31)
Secondary	Frequency of RSVPreF3-specific CD4+ T Cells Expressing at Least 2 Activation Markers, at Month 6 and Month 12 Post-intervention	Among markers expressed are interleukin-2/13/17 (IL-2, IL-13, IL-17), cluster of 40 ligand (CD40L), 41BB, tumour necrosis factor alpha (TNF-a) and interferon gamma (IFN-?), in vitro upon stimulation with RSVPreF3 peptide preparations.	At 6 months and at 12 months after study intervention administration
Secondary	Frequency of RSVPreF3-specific CD8+ T Cells Expressing at Least 2 Activation Markers, up to One Month Post-intervention	Among markers expressed are IL-2, IL-13, IL-17, CD40L, 41BB, TNF-a and IFN-?, in vitro upon stimulation with RSVPreF3 peptide preparations.	At pre-study intervention administration (Day 1) and 1 month after study intervention administration (Day 31)
Secondary	Frequency of RSVPreF3-specific CD8+ T Cells Expressing at Least 2 Activation Markers, at Month 6 and Month 12	Among markers expressed are IL-2, IL-13, IL-17, CD40L, 41BB, TNF-a and IFN-?, in vitro upon stimulation with RSVPreF3 peptide preparations.	At 6 months and at 12 months after study intervention administration