A Phase II randomized trial of RSV vaccination in allogeneic hematopoietic stem cell transplant recipients (RSV-Allo study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre hospitalier universitaire de Liege

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Nov 2024 → ongoing

Decision date (initial)

2024-10-10

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The two main aims of the study are:

- 1) A 2-center phase II trial of anti-RSV vaccination in allo-HSCT recipients. Eligible patients will be first randomized to be part of the RSVPreF (Abrysvo) or the RSVPreF3 OA (Arexvy) arm of the trial, unless one of the two vaccine arms is closed. The design of each vaccine arm are Simon’s two-stage phase II trials (see section 9). Specifically, in each arm, sixteen patients will receive one single i.m. injection of the vaccine (first cohort). If 11 or more of the 16 evaluable patients (i.e. patients with day 28 sampling) achieve a seroconversion (> 5-fold increase in levels of RSV F binding IgG between day 0 (day of vaccine administration) and day 28), 25 additional patients will receive a single injection of the vaccine for a total of 41 evaluable patients. If ten or less of the 16 patients (first stage) or if 29 or less of the 41 patients (second stage) achieve a seroconversion, a second cohort of sixteen patients will receive two injections of the vaccine at 8-10 weeks apart. If 11 or more patients of the second cohort achieve a seroconversion, 25 additional patients will receive two injections of the vaccine at 8 weeks apart for a total of 41 patients for the second cohort (and 57 (if only the first stage was performed in the first cohort) or 82 (if the first and second stages were performed in the first cohort) eligible patients in total). If ten or less of the 16 patients from the first stage of second cohort achieve a seroconversion, the study will be closed for futility after a total of 32 or 57 eligible patients for each vaccine arm. So, according to the observed seroconversion rate, from 64 to 164 eligible patients will be included in the trial.

- 2) A systems biology study aimed at 1) defining a baseline signature predicting response to the vaccine; 2) assessing the impact of one or more dose of the RSV vaccine on the immune system; and 3) at comparing the immune signature of the RSVPreF (Abrysvo) or the RSVPreF3 OA (Arexvy) vaccine. This systems vaccinology study will be performed on samples collected during the phase II study described above as well as in a cohort of 40 healthy control subjects aged 60 years or more who will be randomized 1/1 to receive the RSVPreF (Abrysvo) or the RSVPreF3 OA (Arexvy) vaccine. The signature of each in allo-HSCT and in healthy controls will also be compared.

Conditions and MedDRA coding

allogeneic - Hematopoietic Stem Cell Transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Prior allo-HSCT 3 months to 5 years before first vaccination (any donor type except cord blood transplantation); patients > 5 years are also eligible if they are still on systemic immunosuppressive treatment for chronic GVHD
2. Age > or = 18 years at inclusion
3. Written informed consent

Exclusion criteria 10

1. Known HIV seropositivity
2. Active malignant disease at vaccination
3. Current grade III-IV acute GVHD
4. Ongoing transplant-associated thrombotic microangiopathy (TA-TMA)
5. In vitro T-cell depletion of the graft if vaccination within 6 months after transplantation
6. Rituximab administration < 6 months before inclusion
7. IVIg in the 30 days before vaccination or planned IVIg administration in the 28 days after the last vaccine administration
8. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s) or any related vaccine
9. Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular or subcutaneous injection
10. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. First co-primary endpoint : The primary endpoint will be to assess the efficacy of the each RSVpreF and RSVpreF3 OA vaccines in allo-HSCT recipients. We will use the surrogate marker of seroconversion (see section 7.3 for the definition of response) for assessing vaccine efficacy. Efficacy will be defined as a seroconversion rate > 80% with either one or two doses of the vaccine.
2. Second co-primary endpoint : To define a baseline signature predicting response to RSVpreF and RSVpreF3 OA vaccines using systems vaccinology tools.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre hospitalier universitaire de Liege

Sponsor organisation

Centre hospitalier universitaire de Liege

Address

Avenue De L'hopital 1

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Centre hospitalier universitaire de Liege

Contact name

Principal investigator

Public contact point

Organisation

Centre hospitalier universitaire de Liege

Contact name

Principal investigator

Locations

1 EU/EEA country · 2 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 10 files

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

Application history

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