Clinical trial NCT05921903: A Study on the Immune Response and Safety of an RSV Vaccine When Given to Adults 18 Years of Age and Above Who Received Lung or Kidney Transplant and Are at an Increased Risk of Respiratory Syncytial Virus Lower Respiratory Tract Disease and Compared to Healthy Adults 50 Years of Age and Above
Official title: A Phase 2b, Randomized, Controlled, Open-label Study to Evaluate the Immune Response and Safety of the RSVPreF3 OA Investigational Vaccine in Adults (>=18 Years of Age) When Administered to Lung and Renal Transplant Recipients Comparing 1 Versus 2 Doses and Compared to Healthy Controls (>=50 Years of Age) Receiving 1 Dose
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory syncytial virus
Vaccine
Immunogenicity
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-06-27
Enrollment: 387
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the immunogenicity, safety, and reactogenicity of the RSVPreF3 OA investigational vaccine in an immunocompromised (lung and renal transplant recipients) population and assess whether a second dose of the vaccine increases the immune response.


Eligibility criteria: Inclusion Criteria:

* Participants and/or participant's parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Participants living in the general community or in an assisted-living facility that provides minimal assistance can be enrolled, such that the participant is primarily responsible for self-care and activities of daily living.
* Written or witnessed informed consent obtained from the participant/participant's parent(s)/LAR(s) (participant must be able to understand the informed consent) prior to performance of any study-specific procedure.
* Female participants of nonchildbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and 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 and agreed to continue adequate contraception until study end for this study, and has a negative pregnancy test on the day of and prior to study intervention administration.

Specific inclusion criteria for renal/lung transplant patients:

* A male or female, \>=18 YoA at the time of signing the Informed consent form (ICF) or Informed assent form (IAF).
* Written informed assent obtained from the participant (participant must be able to understand the informed assent) if he/she is less than legal age of consent, or written informed consent obtained from the participant if the participant has achieved legal age of consent.
* Participant who has received an ABO compatible allogeneic renal or lung transplant (allograft) more than 12 months (365 days) prior to the first study intervention administration.
* Participant receiving maintenance immunosuppressive therapy for the prevention of allograft rejection.

Specific inclusion criteria for renal transplant (RTx) patients:

• Participant with stable renal function, stability defined as less than 20% variability between last two results of eGFR or in the opinion of the investigator after investigator review of more than the last two results of eGFRs and based on medical history.

Specific inclusion criteria for lung transplant (LTx) patients:

• Participant with stable lung function, with stability defined as the stability in the FEV1 compared to post-transplant baseline FEV1 and based on medical history of the last 3 months, in the opinion of the investigator.

Specific inclusion criteria for healthy participants:

* A male or female, \>=50 YoA at the time of signing the ICF.
* Healthy participants as established by medical history and clinical examination before entering the study.
* Participants who are medically stable in the opinion of the investigator at the time of first study intervention administration.
* Participants with chronic stable medical conditions with or without specific treatment, such as diabetes mellitus, hypertension, or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable.

Exclusion Criteria:

Medical conditions:

* History of any reaction/ hypersensitivity likely to be exacerbated by any component of the study intervention.
* Acute or chronic clinically significant cardiovascular or hepatic functional abnormality as determined by physical examination or laboratory screening tests.
* Recurrent/uncontrolled neurological disorders or seizures. Participants with medically controlled chronic neurological diseases can be enrolled in the study if their condition will allow them to comply with the requirements of the protocol, with the help of a caregiver if needed.
* Any history of dementia or any medical condition that moderately or severely impairs cognition.
* Any condition which would make IM injection unsafe.
* Significant underlying illness that would prevent completion of the study).
* Acute disease and/or fever at the time of study intervention administration (\>=38°C /100.4°F, oral or axillary). Participants with a minor illness without fever may be enrolled at the discretion of the investigator.
* Bedridden participants.

Prior/Concomitant therapy:

* Use of any other investigational or non-registered product (drug, vaccine, or medical device) up to 30 days before the first dose administration (Day -30 to Day 1), or their planned use during the study period (up to Visit 6).
* Previous vaccination with the study antigen (RSV), including investigational RSV vaccines.
* Unexpected vaccine administration during a study should not occur 30 days prior to the first dose or 30 days after the last dose. For COVID-19 and inactivated/subunit/split influenza vaccines, this window is shortened to 14 days.

Prior/Concurrent clinical study experience:

• Concurrently participating in another active clinical study

Other exclusion criteria:

* Pregnant or lactating female participant.
* Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
* History of chronic alcohol consumption and/or drug abuse
* Participation of any study personnel or their immediate dependents.
* Planned move during the study period that will prohibit participating in the study until study end.

Specific exclusion criteria for renal/lung transplant patients:

* More than one organ transplanted. Dual organ is allowed.
* History of events that may put the participant at increased risk for chronic allograft dysfunction.
* Participant with an episode of allograft rejection over the previous 90 days prior to the first study intervention administration.
* Histologic evidence of chronic allograft injury.
* Active treatment for acute rejection.
* Current diagnosis of malignancy (except non-melanoma skin cancer that does not require systemic therapy).
* Any autoimmune conditions or pIMDs that may put the participant at increased risk.
* Any confirmed or suspected HIV infection, primary immunodeficiency disease or ongoing CMV infection with a viremia \>200 IU/mL.
* Use of anti-CD20 or other B-cell monoclonal antibody agents for the prevention of allograft rejection within 274 days of first dose of study.
* Use of investigational and non-registered immunosuppressants at the local/country level, unless specifically prescribed for the prevention of allograft rejection, and which are in process of approval, approved in other countries and locally available.
* Evidence/high suspicion\\ of noncompliance/nonadherence to use of induction and/or maintenance immunosuppressive therapies.
* Any clinically significant hematologic and/or biochemical laboratory abnormality.

Specific exclusion criteria for RTx patients:

* Previous allograft loss secondary to recurrent primary kidney disease. Multiple consecutive kidney transplants are allowed if the reason is not recurrent primary kidney disease.
* Evidence of significant proteinuria/albuminuria.

Specific exclusion criteria for LTx patients:

* At study intervention administration visit, diagnosis of documented acute pulmonary infection within the 2 prior weeks.
* Patients with diagnosis of chronic lung allograft dysfunction (decrement of \>=20% in FEV1 compared to post-transplant baseline FEV1).

Specific exclusion criteria for healthy participants:

* Any confirmed/suspected immunosuppressive/immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination.
* Unstable serious chronic illness.
* Chronic administration of immune-modifying drugs (\>14 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 -prednisone equivalent ≥20 mg/day, or equivalent. Inhaled, topical and intra-articular 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.

Primary outcomes:
measure: RSV-A serum neutralizing titers expressed as mean geometric increase (MGI) post Dose 2 over post-Dose 1
timeFrame: At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60)
measure: RSV-B serum neutralizing titers expressed as MGI post-Dose 2 over post-Dose 1
timeFrame: At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60)
Secondary outcomes:
measure: RSV-A serum neutralizing titers expressed as Geometric Mean Titers
timeFrame: At Visit 2 in a subset of participants (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: RSV-B serum neutralizing titers expressed as Geometric Mean Titers
timeFrame: At Visit 2 in a subset of participants (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: RSV-A serum neutralizing titers expressed as group geometric mean titers (GMT) ratio
timeFrame: At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: RSV-B serum neutralizing titers expressed as group geometric mean titers (GMT) ratio
timeFrame: At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: RSV-A serum neutralizing titers expressed as mean geometric increase (MGI)
timeFrame: At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: RSV-B serum neutralizing titers expressed as mean geometric increase (MGI)
timeFrame: At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: Cell Mediated Immunity (CMI) response in a subset of participants
timeFrame: At Day 1 (dose 1), at Visit 2 (7-14 days post-dose 1), Visit 3 (30-60 days post dose-1, dose 2 for the RSV_IC_2 group), Visit 4 (Visit 3+30-42 days), Visit 5 (180-210 days post last-dose) and at Visit 6 (350-380 days post last dose)
measure: Percentage of participants with solicited administration site events
timeFrame: Within 7 days post-study intervention administration (i.e., the day of vaccination and 6 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
measure: Percentage of participants with solicited systemic events
timeFrame: Within 7 days post-study intervention administration (i.e., the day of vaccination and 6 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
measure: Percentage of participants with unsolicited adverse events (AEs)
timeFrame: Within 30 days post-study intervention administration (i.e., the day of vaccination and 29 subsequent days, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
measure: Percentage of participants with any serious adverse events (SAEs) after study intervention, SAEs related to study intervention and fatal SAEs
timeFrame: From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
measure: Percentage of participants with any potential immune-mediated disease (pIMDs) after study intervention and pIMDs related to study intervention
timeFrame: From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
measure: Percentage of participants with any AESIs
timeFrame: From Day 1 up to study end (Day 350-380 post last dose, vaccine administered on Day 1 for all groups and Day 30-60 for RSV_IC_2)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Temple
country: United States
facility: GSK Investigational Site
state: Texas
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Birtinya
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Giessen
country: Germany
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Palermo
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Siena
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: A Coruna
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
Study officials:
References: