Workpackage 7

 

Work package number

7

Start date or starting event:

M32

Work package title

Phase I clinical trial

Activity Type[1]

 

Participant number

1

4

5

6

7

 

 

Participant short name

IQUR

UCL

CRP-Santé

3P

ICS

 

 

Person-months per participant:

2.0

0.6

32.6

1.0

0.9

 

 

                   

 

Objectives

A Phase I clinical trial will be conducted in 20 individuals to ensure safety and immunogenicity in humans. Immunogenicity will be tested ex vivo using the assays described in WP3.  

 

Description of work (possibly broken down into tasks), and role of participants

Introduction

This WP includes study design, execution, reporting and evaluation of a phase I clinical trial to demonstrate safety and immunogenicity, based on pre-clinical immunogenicity and toxicology reports developed in previous WPs 1-6.

 

Task 7.1: Design of the study and approvals (IQUR & ICS, M32-M34)

Includes the review of the available evidence from previous stages, the drafting of study protocol and obtaining the approvals to conduct the study from the Clinical Research Ethics Committee (CREC) of Vall d’Hebron Hospital, the Spanish Agency of Medicines and Medical Devices, and any other regulatory requirements at the moment of the study.

 

Task 7.2: Conduction of the study (IQUR & ICS, M34-M42)

Task 7.2.1 Recruitment (ICS);

Recruitment of potential trial participant subjects among healthy adult (≥18 years old) female (without bearing potential) and male volunteers.

Task 7.2.2 Screening (ICS);

Inclusion and exclusion criteria will be considered for all potential trial participants. Screening activities comprise: medical history, clinical examination, and urine pregnancy test if applicable.

Task 7.2.3 Obtaining informed consent (ICS);

Trial candidate subjects will receive fully oral and written information, and should provide their consent to participate in the writing form approved by the CREC.

Task 7.2.4 Randomization (ICS);

Trial subjects allocation will correspond with the code used for packaging the trial vaccine to guarantee concealment and will be assigned randomly.

Task 7.2.5 Vaccine administration (ICS & 3P);

Vaccine will be delivered to ICS from 3P. After confirmation of normal axilar body temperature, verification of inclusion and exclusion criteria, and signed informed consent, assigned vaccine will be administered intramuscular in the deltoid muscle of the non-dominant arm. Further in this document, this will be considered day 0 and timing will be mentioned as number of days since vaccination.

Task 7.2.6 Close monitoring (ICS);

Following the administration of the vaccine, all trial subjects will stay in the observational area for 30 minutes, with appropriate emergency treatment available if needed.

Task7.2.7 Safety follow-up (ICS);

Trial subjects will receive a diary card to record any adverse event until day 21. Concomitant medication, other vaccination, or any new medical condition will be recorded. Safety follow-up visits will be scheduled on days 7 and 21. Routine safety blood test will be done on day 0 and 21. Patients will be contacted by phone 180 days after vaccination to register any serious adverse event between days 21 and 180. Subject will be instructed to contact the investigator immediately in case of perception of any serious sign or symptom. A standard procedure will be in place to report and evaluate any serious adverse event.

 

Task 7.3 Data analysis (ICS & IQUR, M38-M42) The statistical analyses will be performed in two steps. The main analysis will be performed when all data on immunogenicity and safety upon day 21 post vaccination is available. A second analysis will include safety data until day 180 after vaccination.  Descriptive statistics for the vaccination group and for each individual on day 0, 21 and 180 will be provided. Geometric mean titres, seroconversion rates, conversion factors, protection rates, frequency of influenza specific-antibody forming cells and other immunogenicity related parameters will be analysed according to the protocol of the study. Missing or non-evaluable measurements will not be replaced.

 

Task 7.4 Reporting and evaluation. (ICS & IQUR, M38-M42).  A preliminary report will be presented with data upon day 21, followed by an annex study report including data of days 21-180.  Analysis and discussion will be performed on final and cleaned data and published properly.

 

Task 7.5: Seroconversion (ICS & UCL, M36-M43)

A minimal of 30ml of whole blood sample to measure humoral and cell mediated immune response will be taken on days 0 and 21. These samples will be adequately processed, and delivered to CRP-Sante for detailed analysis of the nature and quantity of the immune response.

Sera will be transferred to UCL (Prof Rosenberg) and tested for antibody responses by ELISA to both core protein vector and inserted antigens.

 

Task 7.6: T&B receptor usage (ICS & CRP-SANTÉ, M36-M43)

PBL will be shipped to Luxembourg for full immunological screening. This will be similar to that outlined for murine responses in WP 3.6 and 3.7.

 

 

Deliverables** (brief description and month of delivery)

D 7.1: Report of clinical data proving immunogenicity and safety in volunteers (M42)

Immunological data showing seroconversion and T-cell activity will be processed from the blood samples of trial participants extracted on days 0 and 21 after immunization. Safety data about any local or systemic reactions produced within 180 days after immunization will be analysed and presented.

D 7.2: Seroconversion (M43)

Proof of VLP induced seroconversion. Antibodies specific for IAV generated.

D 7.3: T&B cell receptor usage (M43)

Evidence of systemic anti-IAV immunity



[1]   Please indicate one activity per work package: RTD = Research and technological development; DEM = Demonstration; MGT = Management of the consortium; OTHER = Other specific activities, if applicable (including any activities to prepare for the dissemination and/or exploitation of project results, and coordination activities).