We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04844489
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : June 21, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Autoimmune or Autoinflammatory Diseases HIV Multiple Sclerosis Solid Tumors or Cancers Solid Organ Transplant 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 Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 485 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Study of the Humoral Response to SARS-CoV-2 Variants and of the Cellular Response After Vaccination Against COVID-19 in Immunocompromised People
Actual Study Start Date : April 16, 2021
Estimated Primary Completion Date : April 16, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Blood samples 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

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




Primary Outcome Measures :
  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 [ Time Frame: At the third injection visit and at one, six and twelve months after the last injection ]

Secondary Outcome Measures :
  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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At inclusion visit ]
  4. Anti-RBD IgG level [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
  5. Antibody neutralization title [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: At Day 0, at the third injection visit and at one month after the last injection ]
    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

  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 [ Time Frame: 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 [ Time Frame: At Day 0, at the third injection visit and at one month after the last injection ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 18 years
  • Patients eligible for BNT162b2 vaccination
  • Immunocompromised patients according to one of the following criteria:

    1. Patients with autoimmune or autoinflammatory diseases treated

      1. For at least three months
      2. Having received at least 0.1 mg / kg / day of prednisone (or equivalent) for at least three months
      3. 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))
    2. 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
    3. 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)
    4. Patients with solid tumors or cancers:

      1. Patients who have received active cancer treatment other than chemotherapy (targeted therapy, radiotherapy, surgery, hormone therapy) in the previous month
      2. Patients who have received active cancer treatment with chemotherapy (alone or in combination with immunotherapy, radiotherapy or targeted therapy) in the previous month
      3. 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.
    5. 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04844489


Contacts
Layout table for location contacts
Contact: Anne-Geneviève MARCELIN, MD, PhD +33142177401 anne-genevieve.marcelin@aphp.fr
Contact: Olivier BENVENISTE, MD, PhD olivier.benveniste@aphp.fr

Locations
Layout table for location information
France
Hospital Pitié-Salpêtrière - AP-HP Recruiting
Paris, France, 75013
Contact: Olivier BENVENISTE, MD,PhD    0142161088    olivier.benveniste@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04844489    
Other Study ID Numbers: APHP210305
2021-A00469-32 ( Other Identifier: IDRCB )
First Posted: April 14, 2021    Key Record Dates
Last Update Posted: June 21, 2021
Last Verified: June 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Covid-19
Vaccination
Variants
Neutralizing antibodies
Cellular immunity
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Multiple Sclerosis
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases