Clinical trial • Phase II • Immunology|Haematology
RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP A, STABILIZED PREFUSION F PROTEIN 847A; RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP B, STABILIZED PREFUSION F PROTEIN 847B for Allogeneic hematopoietic stem cell transplantation
Phase II trial of RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP A, STABILIZED PREFUSION F PROTEIN 847A; RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP B, STABILIZED PREFUS…
Overview
- Trial Therapeutic Area
- Immunology|Haematology
- Trial Disease
- Allogeneic hematopoietic stem cell transplantation
- Trial Stage
- Phase II
- Drug Modality
- Vaccine
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 08-07-2024
- First CTIS Authorization Date
- 10-10-2024
Trial design
Randomised, abrysvo (rsvpref) intramuscular vaccine arm versus arexvy (rsvpref3 oa) intramuscular vaccine arm; participants randomized between the two vaccine arms. each arm may use a single i.m. injection (first cohort) or two injections 8-10 weeks apart (second cohort) according to the simon two-stage design.-controlled, adaptive Phase II trial across 2 sites in Belgium.
- Randomised
- Yes
- Comparator
- Abrysvo (RSVPreF) intramuscular vaccine arm versus Arexvy (RSVPreF3 OA) intramuscular vaccine arm; participants randomized between the two vaccine arms. Each arm may use a single i.m. injection (first cohort) or two injections 8-10 weeks apart (second cohort) according to the Simon two-stage design.
- Adaptive
- True - Simon's two-stage Phase II designs per vaccine arm with predefined stopping/expansion rules: in each arm 16 patients receive one injection (first cohort); if >=11/16 evaluable patients seroconvert, expand with additional 25 patients to 41 evaluable; if thresholds not met a second cohort of 16 patients may receive two injections and similar rules apply; study may be closed for futility based on these interim results.
- Target Sample Size
- 204
Eligibility
Recruits 204 paediatric patients.
- Vulnerable Population
- No vulnerable population selected; all participants must provide written informed consent ("Written informed consent" is listed as an inclusion criterion).
Inclusion criteria
- {"criterion_text":"- 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"}
- {"criterion_text":"- Age > or = 18 years at inclusion"}
- {"criterion_text":"- Written informed consent"}
Exclusion criteria
- {"criterion_text":"- Known HIV seropositivity"}
- {"criterion_text":"- Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation"}
- {"criterion_text":"- Active malignant disease at vaccination"}
- {"criterion_text":"- Current grade III-IV acute GVHD"}
- {"criterion_text":"- Ongoing transplant-associated thrombotic microangiopathy (TA-TMA)"}
- {"criterion_text":"- In vitro T-cell depletion of the graft if vaccination within 6 months after transplantation"}
- {"criterion_text":"- Rituximab administration < 6 months before inclusion"}
- {"criterion_text":"- IVIg in the 30 days before vaccination or planned IVIg administration in the 28 days after the last vaccine administration"}
- {"criterion_text":"- 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"}
- {"criterion_text":"- Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular or subcutaneous injection"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Seroconversion used as surrogate marker; definition provided elsewhere in protocol: \"seroconversion (> 5-fold increase in levels of RSV F binding IgG between day 0 (day of vaccine administration) and day 28)\". Assessment based on seroconversion rate (>80% defines efficacy)."}
- {"endpoint_text":"- Second co-primary endpoint : To define a baseline signature predicting response to RSVpreF and RSVpreF3 OA vaccines using systems vaccinology tools.","definition_or_measurement_approach":"Defined using systems vaccinology tools on samples collected during the phase II study and a cohort of 40 healthy control subjects aged 60 years or more randomized 1/1 to receive RSVPreF or RSVPreF3 OA; aims to define baseline signature predictive of vaccine response and compare immune signatures between vaccines."}
Recruitment
- Planned Sample Size
- 204
- Recruitment Window Months
- 36
- Consent Approach
- Written informed consent required. Separate subject information and informed consent forms are listed for patients and healthy volunteers (documents: "L1 _ ICF patients _ fr" and "L1 _ ICF healthy volonteers _ fr").
Geography
- Total Number Of Sites
- 2
- Total Number Of Participants
- 204
Belgium
- Earliest CTIS Part Ii Submission Date
- 05-09-2024
- Latest Decision Or Authorization Date
- 10-10-2024
- Processing Time Days
- 35
- Number Of Sites
- 2
- Number Of Participants
- 204
Sites
- Site Name
- Institut Jules Bordet
- Department Name
- Infectious diseases
- Principal Investigator Name
- Aspasia GEORGALA
- Principal Investigator Email
- aspasia.georgala@hubruxelles.be
- Contact Person Name
- Aspasia GEORGALA
- Contact Person Email
- aspasia.georgala@hubruxelles.be
- Site Name
- Centre hospitalier universitaire de Liege
- Department Name
- Hematology
- Principal Investigator Name
- Frédéric BARON
- Principal Investigator Email
- f.baron@chuliege.be
- Contact Person Name
- Frédéric BARON
- Contact Person Email
- f.baron@chuliege.be
Sponsor
Primary sponsor
- Full Name
- Centre hospitalier universitaire de Liege
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Belgium
Investigational products
- Investigational Product Name
- Abrysvo powder and solvent for solution for injection Respiratory syncytial virus vaccine (bivalent, recombinant)
- Active Substance
- RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP A, STABILIZED PREFUSION F PROTEIN 847A; RESPIRATORY SYNCYTIAL VIRUS, SUBGROUP B, STABILIZED PREFUSION F PROTEIN 847B
- Modality
- Vaccine
- Routes Of Administration
- INTRAMUSCULAR INJECTION
- Route
- Intramuscular injection
- Authorisation Status
- Marketing authorisation (EU/1/23/1752/001)
- Maximum Dose
- 120 µg (max daily), 240 µg (max total)
- Investigational Product Name
- Arexvy powder and suspension for suspension for injection Respiratory Syncytial Virus (RSV) vaccine (recombinant, adjuvanted)
- Active Substance
- RESPIRATORY SYNCYTIAL VIRUS, GLYCOPROTEIN F, RECOMBINANT, STABILISED IN THE PRE-FUSION CONFORMATION, ADJUVANTED WITH AS01E
- Modality
- Vaccine
- Routes Of Administration
- INTRAMUSCULAR INJECTION
- Route
- Intramuscular injection
- Authorisation Status
- Marketing authorisation (EU/1/23/1740/001)
- Maximum Dose
- 120 µg (max daily), 240 µg (max total)
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