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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GlaxoSmithKline Biologicals

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

7 Nov 2023 → 3 Jul 2025

Decision date (initial)

2023-10-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline Biologicals

External identifiers

EU CT number

2023-503951-81-00

ClinicalTrials.gov

NCT05921903

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Others, Safety

To evaluate the humoral immune response against RSV-A following the first and the second dose of RSVPreF3 OA investigational vaccine within 2-dose group in renal and lung SOT patients.
To evaluate the humoral immune response against RSV-B following the first and the second dose of RSVPreF3 OA investigational vaccine within 2-dose group in renal and lung SOT patients.

Secondary objectives 2

1. Secondary-Immunogenicity : To evaluate the humoral immune response to the RSVPreF3 OA investigational vaccine until 12 months post-study intervention administration in all groups. To evaluate the CMI response following RSVPreF3 OA investigational vaccine administration in a subset of participants in all groups.
2. Secondary-Safety To evaluate the safety and reactogenicity following RSVPreF3 OA investigational vaccine administration in all groups.

Conditions and MedDRA coding

Respiratory Syncytial Virus Infections

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. "Inclusion criteria for all participants: • 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 (e.g., completion of the paper diary cards, return for follow-up visits, ability to access and utilize a phone or other electronic communications, have regular contact to allow evaluation during the study). • 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)/LARs (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. Refer to protocol section 10.4.1 for definitions of women of childbearing potential, non childbearing potential, menarche and menopause and protocol section 10.4.2 on adequate contraception. "
2. "Specific inclusion criteria for renal/lung transplant patients: •A male or female participant, ≥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. "
3. 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.
4. 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.
5. "Specific inclusion criteria for healthy participants: • A male or female, ≥50 YoA at the time of signing the Informed consent form (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 6

1. "Medical conditions for all: •History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention. (For details on components of study intervention administered, refer to the study protocol and Arexvy SmPC/Prescribing information). • Acute or chronic clinically significant cardiovascular or hepatic functional abnormality as determined by physical examination or laboratory screening tests. • Recurrent or uncontrolled neurological disorders or seizures. Participants with medically controlled 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 (e.g., completion of the diary cards, attend study site visits). Study participants may decide to assign a caregiver to help them complete some of the study procedures (Refer protocol section 8). • Any history of dementia or any medical condition that moderately or severely impairs cognition. • Any condition which, in the judgment of the investigator, would make IM injection unsafe. • Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival up to study end). • Acute disease and/or fever at the time of study intervention administration. Fever is defined as temperature ≥ 38°C /100.4°F determined by oral or axillary route. However, participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. • Bedridden participants. • Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study."
2. "Prior/Concomitant therapy for all: • Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study intervention administration during the period beginning 30 days before the first dose of study intervention administration (Day -30 to Day 1), or their planned use during the study period (up to Visit 6). • Previous vaccination with the same antigen (RSV) containing vaccine as that of the study intervention, including investigational RSV vaccines. • Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose of study intervention administration and ending 30 days after the last dose of study intervention administration*. In the case of COVID-19 and inactivated/subunit/split influenza vaccines, this time window can be decreased to 14 days before and after each study intervention administration."
3. "Prior/Concurrent clinical study experience for all: • 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 intervention (drug/invasive medical device). "
4. "Other exclusion criteria for all: • 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 as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures. • Participation of any study personnel or their immediate dependents, family, or household members. • Planned move during the study period that will prohibit participating in the study until study end. "
5. "Specific exclusion criteria for renal/lung transplant patients: • More than one organ transplanted (i.e., kidney-liver or kidney-other organ(s) transplanted). Dual organ is allowed (double kidney or double lung). • History of events that, in the opinion of the investigator, may put the participant at increased risk for chronic allograft dysfunction. • Participant with an episode of allograft rejection over the previous 3 months (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 in the opinion of the investigator may put the participant at increased risk. • Any confirmed or suspected HIV infection or primary immunodeficiency disease or ongoing CMV infection with a viremia > 200 IU/mL. • Use of anti-CD20 or other B-cell monoclonal antibody agents (e.g., rituximab) as induction, maintenance and/or therapeutic immunosuppressive therapy for the prevention of allograft rejection within 9 months (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 non-registered and:  available locally through compassionate use programs,  submitted for and pending local/country registration,  approved and registered for use in other countries with well-documented SmPC or Prescribing Information. The name of the active component(s) of these immunosuppressants must be provided in the concomitant medication listing. • Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to use of induction and/or maintenance immunosuppressive therapies. • Any clinically significant* hematologic (hemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, platelet red blood cell count and erythrocyte mean corpuscular volume) and/or biochemical (ALT, AST, creatinine, blood urea nitrogen) laboratory abnormality. Specific exclusion criteria for renal transplant (RTx) patients: • Previous allograft loss secondary to recurrent primary kidney disease. Multiple consecutive kidney transplants are allowed if the reason for a previous allograft loss is not recurrent primary kidney disease. • Evidence of significant proteinuria/albuminuria in the opinion of the investigator. Specific exclusion criteria for lung transplant (LTx) patients: • At study intervention administration visit, diagnosis of documented acute pulmonary infection within the 2 prior weeks, based on the following: clinical, radiological, and physiological deterioration; OR isolation of an organism from a clinically relevant BAL fluid culture. • Patients with diagnosis of chronic lung allograft dysfunction, defined as a decrement of 20% or more in FEV1 compared to post-transplant baseline FEV1. "
6. "Specific exclusion criteria for healthy participants: • Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., current malignancy, HIV) or immunosuppressive / cytotoxic therapy (e.g., medication used during cancer chemotherapy, organ transplantation, or to treat autoimmune disorders), based on medical history and physical examination (no laboratory testing required). • Unstable serious chronic illness. • 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 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 including among others, immunotherapy (e.g., TNF-inhibitors), monoclonal antibodies, antitumoral medication."

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. "•RSV-A serum neutralizing titers expressed as MGI post-Dose 2 (Visit 4*) over post-Dose 1 (Visit 3*) in renal and lung SOT patients in the 2-dose group. "
2. •RSV-B serum neutralizing titers expressed as MGI post-Dose 2 (Visit 4*) over post-Dose 1 (Visit 3*) in renal and lung SOT patients in the 2-dose group.

Secondary endpoints 2

1. "Secondary-Immunogenicity: •RSV-A and RSV-B serum neutralizing titers expressed as: - GMT, at pre-study and all post-study intervention visits in all participants. - Group GMT ratio RSV_HA over RSV_IC at V2-6, & IC_2 over IC_1 V4-6 - MGI at Visit 2 and 3 over Visit 1, in RSV_HA and pooled RSV_IC and at Visit 4-6 in all groups. •CMI response expressed as group GMT of the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells at pre- and all post-study visits in a subset participants."
2. "Secondary-Safety •Percentage of participants reporting each solicited administration site and systemic events with onset within 7 days post-study intervention administration. •Percentage of participants reporting unsolicited AEs within 30 days post-study intervention administration (i.e., the day of vaccination and 29 subsequent days). •Percentage of participants reporting any SAEs, any pIMDs and any AESIs after study intervention administration up to study end."

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GlaxoSmithKline Biologicals

Sponsor organisation

GlaxoSmithKline Biologicals

Address

Rue De L'institut 89

City

Rixensart

Postcode

1330

Country

Belgium

Scientific contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

GlaxoSmithKline Biologicals

Contact name

EU GSK Clinical Trials Call Center

Third parties 14

Locations

3 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications