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AzTrials

Autoimmune or Autoinflammatory DiseasesCOVIVAC-IDNCT04844489

Study of the Humoral Response to SARS-CoV-2 Variants and of the Cellular Response After Vaccination Against COVID-19 in Immunocompromised People

A study testing Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19 in people with Autoimmune or Autoinflammatory Diseases and HIV, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Prospective, multicenter, non-comparative cohort study of immunocompromised people vaccinated against Covid-19 with the aim to know the humoral and cellular response to BNT162b2 vaccination against SARS-CoV-2 variants. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19
Could I receive a placebo?
No, everyone receives an active treatment
How many people
377 participants
Where
1 siteFrance
Study dates
16 Apr 2021to 31 Dec 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age greater than or equal to 18 years
  • Patients eligible for BNT162b2 vaccination
  • Immunocompromised patients according to one of the following criteria:
  • Patients with autoimmune or autoinflammatory diseases treated
  • For at least three months
  • Having received at least 0.1 mg / kg / day of prednisone (or equivalent) for at least three months
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  • Currently receiving at least 5 mg / day of prednisone in combination with an immunosuppressant (methotrexate, cyclosporine, mycophenolate mofetil, rapamycin, azathioprine, cyclophosphamide) or biotherapy (anti-B cells (rituximab and others) anti-TNF, IL- 1, IL-6R, IL-12/23, IL-17, or B7 (CTLA4-Ig)) or a kinase inhibitor (Janus, Tyrosine))
  • HIV-infected patients with a CD4 count <500 / mm3 and a viral load <50 copies / ml on stable antiretroviral therapy for at least 3 months
  • Patients with multiple sclerosis treated with a disease-modifying drug for at least 3 months at a stable dose (teriflunomide, dimethyl-fumarate, fingolimod, ocrelizumab, rituximab, natalizumab)
  • Patients with solid tumors or cancers:
  • Patients who have received active cancer treatment other than chemotherapy (targeted therapy, radiotherapy, surgery, hormone therapy) in the previous month
  • Patients who have received active cancer treatment with chemotherapy (alone or in combination with immunotherapy, radiotherapy or targeted therapy) in the previous month
  • Patients who have received active oncology treatment with one or more immunotherapy (s) in combination with anti-PD1, anti-PD-L1, anti-CTLA4 antibodies without chemotherapy in the previous month.
  • Solid organ transplant patients for more than 3 months who have not received a depleting T agent in the induction protocol, and for> 6 months otherwise
  • Life expectancy of more than 3 months
  • Having been informed about the study and having given their written and informed consent
  • Beneficiaries or beneficiaries of a social security scheme

Who cannot join

  • Patients who may be included in more than one of the sub-cohorts
  • Other vaccination received in the 15 days preceding recruitment or planned in the month following the second vaccine injection
  • Known or suspected allergy to one of the components of the vaccine
  • Severe reaction after previous administration of any influenza vaccine (multiple sclerosis, Guillain-Barré syndrome)
  • Contact subjects of a patient with an undetected documented SARS-CoV-2 infection
  • Evocative signs of COVID-19
Show all 15Show fewer
  • History of documented SARS-CoV-2 infection of less than 3 months (RT-PCR, Lamp PCR, antigen test)
  • Last outbreak of the disease less than 3 months old for patients with Multiple Sclerosis; less than a month old for patients with autoimmune or autoinflammatory diseases
  • For patients with HIV, transient viremia (blip) less than 3 months old
  • Intercurrent infection
  • For organ transplants, episode of cellular or humoral rejection during the 3 months preceding inclusion
  • Healthy volunteers
  • Pregnancy less than 13 weeks old according to the declaration of pregnancy
  • Refusal of participation by the patient
  • Patients subject to legal protection measures

Trial locations and contacts

1 site in 1 country.

France1 site
  • Hospital Pitié-Salpêtrière - AP-HP

    Paris, 75013

Other trials in France

About this study

Prospective, multicenter, non-comparative cohort study of immunocompromised people vaccinated against Covid-19 with the aim to know the humoral and cellular response to BNT162b2 vaccination against SARS-CoV-2 variants. This study will enroll patients in 5 parallel sub-cohorts of the same size, distinct according to the source of the immunosuppression: autoimmune or auto-inflammatory disease, HIV infection, multiple sclerosis, solid cancer, organ transplantation with prospective data collection and constitution of biological collections.

Read the detailed description

The SARS-CoV-2 pandemic represents an extraordinary challenge for global health, it has caused more than 97 million cases of Covid-19 and 2 million deaths worldwide as of January 22, 2021. Vaccination against Covid-19 is an essential weapon to mitigate the consequences of the SARS-CoV-2 pandemic. Its effect in reducing mortality is of course expected in people most vulnerable to Covid-19 such as immunocompromised people.

In general, the immunogenicity of vaccines in immunocompromised populations is conditioned by the nature and intensity of the chronic pathology (s), the age and the treatments received. In addition, the emergence of new variants of SARS-CoV-2 is a major concern today. Three new variants that have rapidly become dominant within their countries have aroused concerns: B.1.1.7 (also known as VOC-202012/01), 501Y.V2 (B.1.351), and P.1 (B.1.1.28.1) and questions are raised about their potential to escape from vaccine-induced immunity. It is therefore important to be able to assess vaccine efficacy in subjects who are fragile with respect to these variants.

The investigators are proposing the establishment of a multicenter cohort study of immunocompromised people vaccinated against Covid-19 with the aim to know the humoral and cellular response to BNT162b2 vaccination against SARS-CoV-2 variants. The primary objective is to evaluate the neutralizing capacity of the antibodies regarding different variants of SARS-CoV-2 after vaccination on 1 month after the first injection, then on 1, 6 and 12 months after the last injection. In-depth immunophenotyping of immune blood cells which analyzes in detail the subpopulations of T lymphocytes and their responses to SARS-CoV-2 will be also analyze before vaccination and after vaccination on 1 month after the first injection, then on 1 month after the last injection. Extensive explorations of the humoral and cellular response to BNT162b2 vaccination will provide crucial data on the potential efficacy of the BNT162b2 vaccine on the recently identified SARS-CoV-2 variants, as well as innovative data on the dynamic of the functional responses of T cells and of the TCR repertoire, the dynamic of which (increase after vaccination, remote contraction) makes it possible to link them to a vaccine response, as has already been done in the context of other vaccination.

This study will provide a better understanding of the biological response to BNT162b2 vaccination in immunocompromised people with respect to the English VOC 202012/01, South African 501Y.V2 variants and any other variants that may emerge. In particular, the investigators are waiting to be able to estimate the proportion of patients whose immunogenicity suggests a reduction in the frequency of severe forms of COVID-19. Conversely, the investigators are waiting to estimate the proportion of patients with a level of immunogenicity too low to hope for good clinical protection against COVID-19. In addition, there are no data on the durability of the biological response to BNT162b2 vaccination.

It is possible that these observations could lead to the implementation of reinforced vaccination protocols for this population, as is already the case for vaccination for hepatitis B vaccination.

Being tested
Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19
Keywords
Covid-19, Vaccination, Variants, Neutralizing antibodies, Cellular immunity
Medical subject headings
Multiple Sclerosis, Neoplasms, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19Other

    Blood samples at:

    • D0 (the day of the injection of the SARS-CoV-2 vaccine),
    • during the 2nd injection as part of the national vaccination campaign (on D28)
    • during the 3rd injection for patients for whom a third injection is recommended (according to the recommendations in force)
    • then to M1, M6 and M12 of the last injection
Study groups in NCT04844489
Study groupRoleWhat they receive
Blood samplesOtherNot described
Receives: Other: Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients with a neutralizing antibody titer greater than 1/10 towards the wild strain and the English VOC 202012/01, South African 501Y.V2 variants and any other variants that may emerge

    Measured: At the third injection visit and at one, six and twelve months after the last injection

Secondary outcomes (9)
  1. Proportion of patients with a positive serology by detection of IgG anti-receptor-binding domain (RBD) antibodies to the Spike protein of SARS-CoV-2 measured by the SARS-CoV technique -2 IgG II Quant assay (Abbott)

    Measured: At second and third injection visits and at one, six and twelve months after the last injection

  2. Proportion of patients with a positive serology by detection of the anti-Spike protein IgG antibodies of SARS-CoV-2 measured by the Euroimmun technique

    Measured: At second and third injection visits and at one, six and twelve months after the last injection

  3. Proportion of patients with positive anti-RBD IgG serology on D0

    Measured: At inclusion visit

  4. Anti-RBD IgG level

    Measured: At second and third injection visits and at one, six and twelve months after the last injection

  5. Antibody neutralization title

    Measured: At second and third injection visits and at one, six and twelve months after the last injection

  6. Neutralization title for antibodies against the wild strain and to the English VOC 202012/01, South African 501Y.V2 variants and any other variants that could be introduced to emerge.

    Measured: At second and third injection visits and at one, six and twelve months after the last injection

  7. Supervised and unsupervised analyzes of deep immunophenotyping of T and B lymphocytes

    Count of CD4 / CD8, B and NK T lymphocyte populations and quantification of Treg lymphocytes on fresh cells. In-depth immunophenotyping of T lymphocytes with naive distributions / memories and activation markers and on naive B distributions / memories and other classically described subpopulations

    Measured: At Day 0, at the third injection visit and at one month after the last injection

  8. Cytometric measurement of intracellular cytokines (IFN, TNF, IL-2, IL4, IL10, IL-17) after stimulation of T lymphocytes by pools of SARS-CoV-2, CMV, EBV and influenza peptides

    Measured: At Day 0, at the third injection visit and at one month after the last injection

  9. Structure and specificity of the TCR (T-cells Receptors) repertoire of blood cells

    High throughput TCR sequencing (Barennes et al, Nat Biotech, 2021) will be performed on separated CD8 and CD4 T cells. Standard diversity metrics, such as V and J gene usage, VJ combination and clonotype frequencies will describe the global repertoire structures before and after vaccination. TCR signatures that could characterize the immune response to vaccination will be define based on the dynamics of sequences. For such studies, analyses are based exclusively on the CDR3 region of the TCRs such as to analyze humans independently of their HLA genotype. Finally, we will search for virus specific TCRs using our curated database (Barennes et al, Nat Biotech, 2021)

    Measured: At Day 0, at the third injection visit and at one month after the last injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2021
  2. Study start16 Apr 2021
  3. Primary completion24 Nov 2022
  4. Study completion31 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
377 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04844489
Sponsor's protocol ID
APHP210305
Other IDs
2021-A00469-32
Acronym
COVIVAC-ID
Status last verified
Jun 2021
First submitted
2 Apr 2021
Last updated
6 Feb 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Louapre C, Belin L, Marot S, Hippolyte A, Januel E, Ibrahim M, Jeantin L, Zafilaza K, Malet I, Charbonnier-Beaupel F, Rosenzwajg M, Soulie C, Marcelin AG, Pourcher V. Three to four mRNA COVID-19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization. Eur J Neurol. 2023 Sep;30(9):2781-2792. doi: 10.1111/ene.15925. Epub 2023 Jun 25.

    PubMed 37310391

Questions about this trial

What is this clinical trial studying?

A study testing Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19 in people with Autoimmune or Autoinflammatory Diseases and HIV, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with a neutralizing antibody titer greater than 1/10 towards the wild strain and the English VOC 202012/01, South African 501Y.V2 variants and any other variants that may emerge (time frame: At the third injection visit and at one, six and twelve months after the last injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04844489, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.

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