RSV OA=ADJ-023: A Study on the Immune Response and Safety of an RSV Vaccine When Given to Adults 50 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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05921903
• Collaborator: (none)
• Enrollment: 375
• Locations: 53
• Arms: 3
• Anticipated Duration (Months): 24.4
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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. The aim of the study is to prevent severe Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease (LRTD).

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Biological: RSVPreF3 OA Investigational Vaccine	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 375 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: This study is an open label study. Potential bias will be reduced by central randomization.
• Primary Purpose: Prevention
• 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 (≥50 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
• Anticipated Study Start Date: Jul 31, 2023
• Anticipated Primary Completion Date: Sep 9, 2024
• Anticipated Study Completion Date: Aug 13, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RSV_IC_1 group Immunocompromised (IC) patients receiving 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1).	Biological: RSVPreF3 OA Investigational Vaccine; The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).
Experimental: RSV_IC_2 group Immunocompromised (IC) patients receiving 2 doses of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1) and Visit 3 (Visit 1 + 30-60 days).	Biological: RSVPreF3 OA Investigational Vaccine; The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).
Active Comparator: RSV_HA group Healthy participants receiving 1 dose of RSVPreF3 OA investigational vaccine at Visit 1 (Day 1).	Biological: RSVPreF3 OA Investigational Vaccine; The investigational vaccine will be administered intramuscularly as 1 dose to RSV_IC_1 and RSV_HA groups, and 2 doses to RSV_IC_2 group).

Outcome Measures

Primary Outcome Measures

1. RSV-A serum neutralizing titers expressed as mean geometric increase (MGI) post Dose 2 over post-Dose 1 [At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60)]

   The analysis is performed on the renal and lung SOT patients in the 2-dose group.

2. RSV-B serum neutralizing titers expressed as MGI post-Dose 2 over post-Dose 1 [At Visit 4 (Visit 3 + 30-42 days) versus Visit 3 (Day 30-60)]

   The analysis is performed on the renal and lung SOT patients in the 2-dose group.

Secondary Outcome Measures

1. RSV-A serum neutralizing titers expressed as geometric mean titers (GMT) [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)]

   RSV-A serum neutralizing titers expressed as group GMT ratio RSV_HA group over RSV_IC group (pooled RSV_IC_1 and RSV_IC_2 groups) is assessed at Visit 2 (in a subset of participants) and Visit 3, and RSV_IC_2 over RSV_IC_1, RSV_HA over RSV_IC_1, and RSV_HA over RSV_IC_2) at Visit 4, Visit 5 and Visit 6.

2. RSV-B serum neutralizing titers expressed as geometric mean titers (GMT) [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)]

   RSV-B serum neutralizing titers expressed as group GMT ratio RSV_HA group over RSV_IC group (pooled RSV_IC_1 and RSV_IC_2 groups) is assessed at Visit 2 (in a subset of participants) and Visit 3, and RSV_IC_2 over RSV_IC_1, RSV_HA over RSV_IC_1, and RSV_HA over RSV_IC_2) at Visit 4, Visit 5 and Visit 6.

3. Cell Mediated Immunity (CMI) response in a subset of participants [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)]

   CMI response is expressed as group geometric mean of the frequency of RSVPreF3-specific CD4+ and/or CD8+ T cells expressing at least 2 activation markers including at least one cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL- 13 and IL-17. The CMI is measured in a subgroup consisting of participants with renal and lung SOT (from 1-dose group and 2-dose group) and healthy participants.

4. Percentage of participants with solicited administration site events [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)]

   Assessed solicited administration site events included pain, redness and swelling, at the injection site.

5. Percentage of participants with solicited administration site events and solicited systemic events [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)]

   Assessed solicited systemic events included fever, myalgia, arthralgia, headache, and fatigue.

6. Percentage of participants with unsolicited adverse events (AEs) [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)]

   An unsolicited AE is an AE that was not included in the list of solicited events. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.

7. Percentage of participants with serious adverse events (SAEs) [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)]

   A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study participant.

8. Percentage of participants with any serious adverse events (SAEs), SAEs related to study intervention and fatal SAEs [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)]

   A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study participant.

9. Percentage of participants with any potential immune-mediated disease (pIMDs) and pIMDs related to study intervention [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)]

   Potential immune-mediated diseases (pIMDs) are a subset of AEs of special interest (AESIs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

10. Percentage of participants with any AESIs [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)]

    AESIs are AEs of special interest. Along with pIMDs, they include also the acute rejection (specific to renal and lung SOT patients) and Atrial fibrillation (AF).

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

• 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 prior to performance of any study-specific procedure.

• A male or female, ≥50 YoA at the time of signing the Informed consent form (ICF).

• 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:

• 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:

• 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.

• 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). However, 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 (double kidney or double lung).

• 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 renal transplant (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 lung transplant (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% or more 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Phoenix	Arizona	United States	85013
2	GSK Investigational Site	Chicago	Illinois	United States	60612
3	GSK Investigational Site	Iowa City	Iowa	United States	52242
4	GSK Investigational Site	Lexington	Kentucky	United States	40536
5	GSK investigational Site	Minneapolis	Minnesota	United States	55455
6	GSK Investigational Site	Saint Louis	Missouri	United States	63110
7	GSK Investigational Site	Omaha	Nebraska	United States	68198
8	GSK Investigational Site	New York	New York	United States	10032
9	GSK Investigational Site	New York	New York	United States	10065
10	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
11	GSK Investigational Site	Dallas	Texas	United States	76502
12	GSK Investigational Site	Birtinya	Queensland	Australia	4556
13	GSK Investigational Site	Herston	Queensland	Australia	4029
14	GSK Investigational Site	Woolloongabba	Queensland	Australia	4102
15	GSK Investigational Site	Adelaide	South Australia	Australia	5000
16	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
17	GSK Investigational Site	Edmonton	Alberta	Canada	T6G 2B7
18	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
19	GSK Investigational Site	London	Ontario	Canada	N6A 5A5
20	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
21	GSK Investigational Site	Montreal	Quebec	Canada	H2X 3H9
22	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1J 2G2
23	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
24	GSK Investigational Site	Giessen	Hessen	Germany	35392
25	GSK Investigational Site	Kaiserslautern	Rheinland-Pfalz	Germany	67655
26	GSK Investigational Site	Milano	Lombardia	Italy	20122
27	GSK Investigational Site	Milano	Lombardia	Italy	20132
28	GSK Investigational Site	Pavia	Lombardia	Italy	27100
29	GSK Investigational Site	Palermo	Sicilia	Italy	90127
30	GSK Investigational Site	Siena	Toscana	Italy	53100
31	GSK Investigational Site	Aichi		Japan	466-8650
32	GSK Investigational Site	Aichi		Japan	470-1192
33	GSK Investigational Site	Fukuoka		Japan	814-0180
34	GSK investigational Site	Hyogo		Japan	662-0918
35	GSK Investigational Site	Kumamoto		Japan	861-8520
36	GSK Investigational Site	Kyoto		Japan	606-8507
37	GSK Investigational Site	Okayama		Japan	700-8558
38	GSK Investigational Site	Tokyo		Japan	160-0017
39	GSK Investigational Site	Tokyo		Japan	193-0998
40	GSK Investigational Site	Seoul	Korea	Korea, Republic of	03722
41	GSK Investigational Site	Seoul	Korea	Korea, Republic of	110-774
42	GSK Investigational Site	Seoul	Korea	Korea, Republic of	138-736
43	GSK Investigational Site	Santander	Cantabria	Spain	39011
44	GSK Investigational Site	Barcelona	Catalonia	Spain	08907
45	GSK Investigational Site	A Coruna	Coruna	Spain	15006
46	GSK Investigational Site	Majadahonda	Madrid	Spain	28222
47	GSK Investigational Site	Barcelona		Spain	08036
48	GSK Investigational Site	Córdoba		Spain	14004
49	GSK Investigational Site	Madrid		Spain	28007
50	GSK Investigational Site	Madrid		Spain	28034
51	GSK Investigational Site	Madrid		Spain	28040
52	GSK Investigational Site	Madrid		Spain	28041
53	GSK investigational Site	Sevilla		Spain	41013

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT05921903
• Other Study ID Numbers: 219900; 2023-503951-81-00
• First Posted: Jun 27, 2023
• Last Update Posted: Jun 27, 2023
• Last Verified: Jun 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by GlaxoSmithKline: Respiratory syncytial virus; Vaccine; Immunogenicity; Safety
• Additional relevant MeSH terms: Respiratory Syncytial Virus Infections

Study Results

No Results Posted as of Jun 27, 2023