A phase-2b controlled study to evaluate the humoral and cellular immune response and safety following one and two doses of an adjuvanted RSV subunit vaccine in immunocompromised patients aged 18 years and older.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

10 Sep 2024 → ongoing

Decision date (initial)

2024-09-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GlaxoSmithKline Pharma GmbH

External identifiers

EU CT number

2024-513187-25-00

ClinicalTrials.gov

NCT06597916

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Prophylaxis

To assess the Arexvy-induced humoral response after second vaccine dose over first vaccine dose with Arexvy in immunocompromised patients ≥ 18 YoA.

Secondary objectives 3

1. To assess safety and tolerability of the first and second dose of Arexvy in immunocompromised patients.
2. To evaluate the Arexvy-induced humoral responses after the first and second dose of Arexvy from baseline up to 12 months post last dose in immunocompromised patients ≥ 18 YoA and healthy controls ≥ 60 YoA (receiving only one dose of Arexvy).
3. To assess vaccine antigen-specific cellular immune response after first and second dose of Arexvy and up to 12 months after the last dose in immunocompromised patients ≥ 18 YoA and after one dose of Arexvy in healthy controls ≥ 60 YoA.

Conditions and MedDRA coding

Respiratory syncytial virus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants who, in the opinion of the investigator, can understand and will comply with the requirements of the protocol.
2. Participants who can give written informed consent prior to study entry and performance of any study-specific procedure.
3. Female participants of childbearing potential may be enrolled in the study if the participant has practiced adequate contraception as described in chapter 6.5.1. from 1 month prior to first Arexvy vaccination and agreed to continue adequate contraception for at least 1 month after completion of the last study intervention administration, and has a negative pregnancy test on the day of first vaccination prior to vaccine application.
4. Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, and post-menopause.
5. 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.
6. Participants with chronic medical conditions with or without specific treatment are allowed to participate in this study if considered by the investigator as medically stable.

Exclusion criteria 18

1. Previous RSV vaccination, including investigational RSV vaccines.
2. Known hypersensitivity to a component of the study vaccine (Arexvy).
3. Acute infection and/or fever at the time of study vaccine administration (>=38°C oral, tympanic or axillary). Participants with a minor illness without fever may be enrolled at the discretion of the investigator.
4. Acute or chronic clinically significant/unstable disease of the cardiovascular, renal, hepatic or neurological organ system (such as hemodialysis, liver cirrhosis (Child-Pugh class C), uncontrolled seizures etc.).
5. Significant underlying illness that would prevent completion of the study.
6. Contraindication for i. m. injection.
7. Use of any other investigational or non-registered product (drug, vaccine, or medical device) less than 30 days before the first dose administration (Day -30 to Day 1), or their planned use during the study period / participation (up to 12 months after last vaccination).
8. Concurrently participating in another active clinical study that includes the application of investigational products (medication, vaccine, medical devices).
9. Participant received other vaccinations starting from 30 days prior to the first dose and ending 30 days after the last dose. For COVID-19 and influenza vaccines a 14 day interval applies.
10. Pregnant or lactating female participant.
11. Female participant planning to become pregnant or planning to discontinue contraceptive precautions.
12. History of ongoing chronic alcohol consumption and/or drug abuse.
13. Participation of any study personnel or their immediate dependents.
14. Any history of dementia or any medical condition that moderately or severely impairs cognition
15. Expected unavailability for the planned study visits.
16. Administration of immunoglobulins and/or any blood products or plasma derivatives within three months before first dose of Arexvy) and during the entire study participation.
17. A confirmed or suspected primary immunodeficiency disease or HIV infection.
18. Evidence or high suspicion, in the opinion of the investigator, of non-compliance or non-adherence to the use of induction and/or maintenance immunosuppressive therapies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Fold increase of RSV-A and -B-specific neutralizing titers 30-60 days (V5) after the second dose relative to titers 30-60 days (V3) after the first dose in immunocompromised patients. Analysis will be performed by group and on the pooled immunocompromised patient.

Secondary endpoints 12

1. RSV-A and -B-specific neutralizing antibody (NT) and PreF3-specific IgG (ELISA) levels from baseline to up to 12 months post last dose by group and on the pooled immunocompromised patients and in controls.
2. RSV-A and -B-specific neutralizing antibody (NT) and PreF3-specific IgG (ELISA) increase above baseline (V1) at all visits (V2-V7) by group and on the pooled immunocompromised patients and in controls.
3. Seroresponse rate (increase in NT/IgG ELISA) of participants per group at all post-first dose visits over baseline by group and on the pooled immunocompromised patients and in controls.
4. Antibody decline (NT/IgG ELISA) after first and second dose of Arexvy in immunocompromised patients by group and on the pooled immunocompromised patients and in controls.
5. Antibody decline (NT/IgG ELISA) after one dose of Arexvy the healthy control group ≥60 YoA.
6. RSV-A and -B-specific neutralizing antibody (NT) and PreF3-specific IgG (ELISA) from baseline to 12 months post last dose in immunocompromised patients by group and on the pooled immunocompromised patients and in controls and compared to controls.
7. RSV-A and -B-specific neutralizing antibodies and PreF3-specific IgG (ELISA) antibody decline after second dose in immunocompromised patients per group and pooled compared to decline in controls after first dose up to 12 months post last dose.
8. Cytokine production after RSV PreF3-specific PBMC restimulation such as IFN-g and IL-2 (V1-V7) in immunocompromised patients per group and controls.
9. Participants reporting solicited local and systemic AEs (up to 7 days post V1 and V3)
10. Participants reporting unsolicited (up to 30 days post V1 and V3) adverse events
11. Participants reporting SAEs, and AEs of special interest (atrial fibrillation, pIMD) from patient notification during the whole study period.
12. Cases of death after application of the first dose up to 12 months post last dose.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Institute of Specific Prophylaxis and Tropical Medicine

Public contact point

Organisation

Medical University Of Vienna

Contact name

Institute of Specific Prophylaxis and Tropical Medicine

Locations

1 EU/EEA country · 1 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

Documents 13 files

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

Application history

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