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.

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05590403

Collaborator

(none)

1,520

Enrollment

Arms

15.8

Anticipated Duration (Months)

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Biological: RSVPreF3 OA investigational vaccine Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1520 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Observer-blind for Cohort 1 (Day1-Day 31) and single-blind afterwards and open-label for Cohort 2

Primary Purpose:

Prevention

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.

Anticipated Study Start Date :

Oct 28, 2022

Anticipated Primary Completion Date :

Mar 14, 2023

Anticipated Study Completion Date :

Feb 21, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adults HA-RSV Group Healthy adults (HA) 50-59 YOA, who receive 1 dose of RSVPreF3 OA investigational vaccine at Day 1.	Biological: RSVPreF3 OA investigational vaccine One dose administered intramuscularly at Day 1.
Placebo Comparator: Adults HA-Placebo Group HA 50-59 YOA, who receive 1 dose of placebo at Day 1.	Drug: Placebo One dose administered intramuscularly at Day 1.
Experimental: Adults AIR-RSV Group Adults at increased risk (AIR) 50-59 YOA, who receive 1 dose of RSVPreF3 OA investigational vaccine at Day 1.	Biological: RSVPreF3 OA investigational vaccine One dose administered intramuscularly at Day 1.
Placebo Comparator: Adults AIR-Placebo Group Adults AIR 50-59 YOA, who receive 1 dose of placebo at Day 1.	Drug: Placebo One dose administered intramuscularly at Day 1.
Experimental: OA-RSV Group Older adults (OA) ≥60 YOA, who receive 1 dose of RSVPreF3 OA investigational vaccine at Day 1.	Biological: RSVPreF3 OA investigational vaccine One dose administered intramuscularly at Day 1.

Outcome Measures

Primary Outcome Measures

RSV-A neutralization antibody titers expressed as group geometric mean titer (GMT) ratio in healthy participants compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)]
RSV-A neutralization antibody titers expressed as group seroresponse rate (SRR) difference in healthy participants compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)]
RSV-B neutralization antibody titers expressed as group GMT ratio in healthy participants compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)]
RSV-B neutralization antibody titers expressed as group SRR difference in healthy participants compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)]
RSV-A neutralization antibody titers expressed as group GMT ratio in participants at increased risk of RSV-LRTD compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)]
RSV-A neutralization antibody titers expressed as group SRR difference in participants at increased risk of RSV-LRTD compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)]
RSV-B neutralization antibody titers expressed as group GMT ratio in participants at increased risk of RSV-LRTD compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31)]
RSV-B neutralization antibody titers expressed as group SRR difference in participants at increased risk of RSV-LRTD compared to OA [1 month after the RSVPreF3 OA investigational vaccine administration (Day 31) compared to baseline (Day 1)]

Secondary Outcome Measures

Percentage of participants reporting each solicited administration site event (pain, redness and swelling) [Within 4 days after study intervention administered on Day 1]
Percentage of participants reporting each solicited systemic event (fever, headache, muscle pain, joint pain, tiredness) [Within 4 days after study intervention administered at Day 1]
Percentage of participants reporting unsolicited adverse events (AEs) [Within 30 days after study intervention administered at Day 1]
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.
Percentage of participants reporting any serious adverse events (SAEs) [After study intervention administration (Day 1) up to Month 6]
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.
Percentage of participants reporting any potential immune mediated diseases (pIMDs) [After study intervention administration (Day 1) up to Month 6]
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.
Percentage of participants reporting SAEs related to study intervention administration [After study intervention administration (Day 1) up to study end (Month 12)]
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.
Percentage of participants reporting pIMDs related to study intervention administration [After study intervention administration (Day 1) up to study end (Month 12)]
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.
Percentage of participants reporting any fatal SAEs [After study intervention administration (Day 1) up to study end (Month 12)]
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.
RSV-A neutralization antibody titers expressed as GMT [At pre-study intervention administration, 1 month, 6 months and at 12 months after study intervention administration]
RSV-B neutralization antibody titers expressed as GMT [At pre-study intervention administration, 1 month, 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 [At pre-study intervention administration, 1 month, 6 months and at 12 months after study intervention administration]
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-α) and interferon gamma (IFN-γ), in vitro upon stimulation with RSVPreF3 peptide preparations.
Frequency of RSVPreF3-specific CD8+ T cells expressing at least 2 activation markers [At pre-study intervention administration, 1 month, 6 months and at 12 months after study intervention administration]
Among markers expressed are IL-2, IL-13, IL-17, CD40L, 41BB, TNF-α and IFN-γ, in vitro upon stimulation with RSVPreF3 peptide preparations.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.
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