Clinical trial NCT04748471: Immunogenecity and Safety of VaccinemRNA-1273 in Elderly Volunteers (Over 65 y) Compared to Younger Ones (18-45y)
Official title: A Phase II Trial Assessing Immunogenicity and Safety of SARS-CoV-2 Vaccine mRNA-1273 in Volunteers Aged of 65 Years or More Compared to Participants 18-45 Years Old
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Prevention of COVID19
Keywords: Vaccinology
Infectiology
Vaccine
COVID-19
Immunity
Immune
Cells
Mucosal immunity
Autoimmunity
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2021-02-10
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study aims to evaluate the immunogenicity of Moderna mRNA-1273 vaccine in volunteers aged 65 years or more compared to volunteers aged 18-45 years, over 24 months duration. It will provide necessary data on the early immunological response to the vaccine and its evolution in quantitative and qualitative terms. This study will allow establishing how aging influences the response to the vaccine and help to adapt the vaccinal plan. For instance it will suggest the necessity of a vaccination booster.

Detailed description: Phase II, comparative, non-randomized trial assessing the immunogenicity and safety of vaccine candidate Moderna-1273 against SARS-CoV-2. A total of 180 volunteers will be included and vaccinated (2 doses, at day 1 and day 29), divided in 3 groups (60 volunteers 18 - 45 years old, 60 volunteers 65 - 74 years old, 60 volunteers at least 75 years old). Vaccinated volunteers of the three arms will be immune-monitored during 24 months via a battery of in vitro and ex vivo tests to comprehensively assess the course of humoral, cellular and mucosal immunity over time.

Eligibility criteria: Inclusion Criteria:

1. At least 65 years old, at least 75 years old or 18 to 45 years old, depending on the group of inclusion.
2. Healthy adults, or stable medical condition for adults with pre-existing medical conditions. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during 3 months before enrolment, nor expected to require any significant change in therapy or hospitalization for worsening disease in foreseeable future.
3. Understands and agrees to comply with the study procedures (visits, phone calls) and provides written free informed consent.
4. Able to comply with study procedures based on Investigator judgement.
5. Affiliated to a social security system, (except state medical aid)

Exclusion criteria:

1. Subject is ill or febrile (body temperature ≥ 38.0°C) within 72 prior hours or and/or symptoms suggestive of COVID-19 within the past 14 days at enrolment visit.

   (Ill or febrile participants may be re-scheduled within the inclusion period when no longer presenting symptoms)
2. History of documented COVID-19 (PCR+, antigenic test+ or chest TDM+ or serology SARS-CoV-2+) prior to first vaccine administration
3. Subjects with positive serology to SARS-CoV-2 at the enrolment visit
4. Subjects who already received another anti-SARS-CoV-2-vaccine
5. Subjects who received BCG given within the last year.
6. An immediate family member or household member of study staff.
7. Use of immunosuppressive drugs like e.g. corticosteroids at a dosage \> 10mg/day (excluding topical preparations and inhalers) within 3 months prior to enrolment or 6 months for chemotherapies
8. Received immunoglobulin or other blood product within 3 months prior to enrolment or planned receipt of immunoglobulin or a blood product through study completion.
9. Received any vaccination within 4 weeks prior to first injection or plan to receive a licensed vaccine 4 weeks after the last injection.
10. History of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as rush, respiratory difficulty, angioedema and abdominal pain to vaccines, or history of allergic reaction likely to be exacerbated by any component of the anti-SARS-CoV-2-vaccine.
11. History of severe allergic event
12. Participation in another investigational clinical study (Jardé 1 or Jardé 2) within 4 weeks before the enrolment visits or planned before the study completion.
13. Known HIV, active HCV or HBV infection
14. Any pathological condition, such as cancer, which may be susceptible of reducing immunity response
15. Any bleeding disorder considered as contraindication to intramuscular injection or phlebotomy
16. The use of investigational Ig, investigational monoclonal antibodies or convalescent serum are not allowed during the study
17. Any condition which in the opinion of the investigator may interfere with the aim of the study
18. Pregnant or breastfeeding or positive pregnancy urine test at enrolment visit.
19. Woman in childbearing without efficacious contraception (in the opinion of the investigator) for 31 days after treatment (2nd vaccine injection)
20. People under legal protection measure (tutorship, curatorship or safeguard measures)

Primary outcomes:
measure: Titers of anti-SARS-CoV-2 Spike IgG Immunoglobulin in sera
timeFrame: Day 57 (28 days after second injection of mRNA-1273)
Secondary outcomes:
measure: Anti SARS-CoV -2 IgG, IgA and IgM (total and subclasses IgG1-4) as measured by ELISA.
timeFrame: From Day 1 to Month 24
measure: Anti-SARS-CoV-2 neutralizing antibody (in vitro neutralisation assay.
timeFrame: From Day 1 to Month 24
measure: Anti-SARS-CoV-2 -specific neutralizing antibody (Pseudo neutralisation assay using lentiviral phenotypes carrying specific SARS-Cov-2 proteins.
timeFrame: From Day 1 to Month 24
measure: Fluorospot assays (TH1, TH2, TH17, Cytotoxicity). Phenotyping of antigen specific T-Cells via Mass cytometry, B cell repertoire and memory
timeFrame: From Day 1 to Month 24
measure: Mucosal SARS-CoV-2 -specific antibody via measure of sIgA, sIgM and IgG in saliva by specific home-made and commercially available ELISA assays.
timeFrame: From Day 1 to Month 24
measure: Functionality of mucosal sIgA and sIgM by Antibody Dependent Cellular Cytotoxicity (ADCC) assay specific for SARS-CoV-2 mucosal IgA and IgM
timeFrame: From Day 1 to Month 24
measure: Local and systemic reactogenicity
timeFrame: From Day 1 to Month 24
measure: Determination of autoimmunity markers such as antibodies Anti-nuclear (unit measure: titers)
timeFrame: From Day 1 to Month 24
measure: Determination of autoimmunity markers such as antibodies Anti-ACL, Anti-β2-GP1, Rheumatoid factor (unit measure: U/L)
timeFrame: From Day 1 to Month 24
measure: Determination of autoimmunity markers such as antibodies Anti-GM1, Anti-MAG ( unit measure: pos/ne)
timeFrame: From Day 1 to Month 24
Other outcomes:
Locations:
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Odile LAUNAY, Professor
role: PRINCIPAL_INVESTIGATOR
References: