Immunogenecity and Safety of VaccinemRNA-1273 in Elderly Volunteers (Over 65 y) Compared to Younger Ones (18-45y) (CoviCompareM)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prevention of COVID19
• Intervention / Treatment: Biological: mRNA-1273

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.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Odile LAUNAY, Professor; Phone Number: 01 58 41 28 58; Email: odile.launay@aphp.fr
• Study Contact Backup: Name: Jean Daniel LELIEVRE, Professor; Phone Number: 01 49 81 24 09; Email: jean-daniel.lelievre@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 18-45 years old; 18 - 45 years old (60 volunteers), 2 injections of mRNA-1273, at day 1 and day 29	Biological: mRNA-1273; SARS-CoV-2 vaccine
Experimental: 65-74 years old; 65 - 74 years old (60 volunteers), 2 injections of mRNA-1273, at day 1 and day 29	Biological: mRNA-1273; SARS-CoV-2 vaccine
Experimental: At least 75 years old; At least 75 years old (60 volunteers), 2 injections of mRNA-1273, at day 1 and day 29	Biological: mRNA-1273; SARS-CoV-2 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers of anti-SARS-CoV-2 Spike IgG Immunoglobulin in sera	Anti-SARS-CoV-2 Spike specific IgG Immunity acquisition	Day 57 (28 days after second injection of mRNA-1273)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti SARS-CoV -2 IgG, IgA and IgM (total and subclasses IgG1-4) as measured by ELISA.	Assessment of humoral immunity-systemic response	From Day 1 to Month 24
Anti-SARS-CoV-2 neutralizing antibody (in vitro neutralisation assay.	Assessment of humoral immunity-systemic response	From Day 1 to Month 24
Anti-SARS-CoV-2 -specific neutralizing antibody (Pseudo neutralisation assay using lentiviral phenotypes carrying specific SARS-Cov-2 proteins.	Assessment of humoral immunity-systemic response	From Day 1 to Month 24
Fluorospot assays (TH1, TH2, TH17, Cytotoxicity). Phenotyping of antigen specific T-Cells via Mass cytometry, B cell repertoire and memory	Assessment of cellular immunity acquisition	From Day 1 to Month 24
Mucosal SARS-CoV-2 -specific antibody via measure of sIgA, sIgM and IgG in saliva by specific home-made and commercially available ELISA assays.	Assessment of mucosal immunity	From Day 1 to Month 24
Functionality of mucosal sIgA and sIgM by Antibody Dependent Cellular Cytotoxicity (ADCC) assay specific for SARS-CoV-2 mucosal IgA and IgM	Assessment of mucosal immunity	From Day 1 to Month 24
Local and systemic reactogenicity	Clinical safety evaluation	From Day 1 to Month 24
Determination of autoimmunity markers such as antibodies Anti-nuclear (unit measure: titers)	Biological safety evaluation	From Day 1 to Month 24
Determination of autoimmunity markers such as antibodies Anti-ACL, Anti-β2-GP1, Rheumatoid factor (unit measure: U/L)	Biological safety evaluation	From Day 1 to Month 24
Determination of autoimmunity markers such as antibodies Anti-GM1, Anti-MAG ( unit measure: pos/ne)	Biological safety evaluation	From Day 1 to Month 24

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Odile LAUNAY, Professor, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): February 10, 2021
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): January 25, 2023

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: February 6, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): February 10, 2021
• Last Update Submitted That Met QC Criteria: February 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Vaccine; COVID-19; Immunity; Vaccinology; Infectiology; Immune; Cells; Mucosal immunity; Autoimmunity
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: APHP201504; 2020-005889-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Data are available upon reasonable request The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No