Clinical trial NCT04952766: Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
Official title: Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplant
Myeloma
Cancer
Hematologic Malignancy
Multiple Sclerosis
Hypergammaglobulinemia
Malignant Tumor
Hiv
Diabetes Type 2
Keywords: SARS-CoV-2
BNT162b2 vaccine
antibody
neutralization
mucosa
immunocompromised
healthy subject
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2021-07-07
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants wil have at each of the 4 visits (for patients starting at month 1) or 5 visits (for patients starting at month 0):

1. a venipuncture sample of 2 dry tubes of 7 mL (less than 30 mL in total) to make up 3 aliquots and
2. a nasopharyngeal swab (optional). The aliquots of serum / plasma and the nasopharyngeal swab will be stored at -80°C until sent to the Pasteur Institute.
Primary purpose: OTHER

Brief summary: The primary endpoint of this study is to compare the humoral response (titre and neutralizing capacity of induced antibodies) against SARS-CoV-2 following vaccination with BNT162b2 (Pfizer BioNTech) in immunocompromised persons, in comparison to healthy subject. Secondary objectives are to evaluate the humoral response in the nasal mucosa, and the capacity of antibodies to neutralize emerging variants of concerns and to prevent COVID-19.

Detailed description: The serious, even fatal, forms of COVID-19 preferentially affect elderly and fragile subjects. Among these populations at risk, people who are immunocompromised (either by a disease and / or its treatment) have a theoretical risk of responding less well to a preventive vaccination.

The main objective of this study aims to compare the vaccine response of immunocompromised people with healthy subjects (non-immunocompromised), i.e. to assess the serum humoral response (titre and neutralizing capacity of the antibodies induced) following vaccination with ComirnatyTM (i.e. BNT162b2, an anti-SARS-CoV-2 vaccine from Pfizer BioNTech) in immunocompromised persons in comparison to healthy subjects (non-immunocompromised).

Secondary objectives are as follows:

* To evaluate the antibody response in the nasal mucosa (titre and neutralizing capacity of the antibodies induced, collected by means of a nasopharyngeal swab) following vaccination with ComirnatyTM in immunocompromised people as compared to healthy subjects (vaccinated either with two doses of ComirnatyTM or, in a subgroup, with one dose of Astra Zeneca's VaxzeriaTM followed by one dose of ComirnatyTM).
* Evaluate the serum and mucosal antibody response (titre and neutralizing capacity of the antibodies induced) against emerging strains of SARS-CoV-2 (so-called Alpha, Beta, Gamma, Delta strains).
* Evaluate the post-vaccination clinical protection against the risk of COVID-19 infection (incident cases after vaccination).

Eligibility criteria: Inclusion Criteria:

* Adult volunteers to be vaccinated with the ComirnatyTM vaccine and to participate in the study, belonging to one of the following groups:

  * Group of immunocompromised (15 participants per immunosuppression subgroup):

    * Kidney transplant
    * Extracorporeal dialysis
    * Solid cancer under chemotherapy and / or radiotherapy
    * Myeloma under chemotherapy
    * Hematologic malignancies under chemotherapy
    * Diseases treated with anti CD20 (or patients not treated at the time of the vaccine but who will be immediately after)
    * Multiple sclerosis under anti CD20 (or patients not treated at the time of the vaccine but who will be immediately after)
    * Common variable immune deficiency or other causes of severe hypogammaglobulinemia requiring chronic treatment with polyvalent immunoglobulin
    * Malignant tumor under anti-PD1 or anti-PDL1
    * People living with HIV
    * Complicated type 2 diabetes (with micro and / or macroangiopathy)
  * Group of non-immunocompromised subjects (controls, n = 75)

    * 60 people vaccinated with the ComirnatyTM
    * 15 people vaccinated with Astra Zeneca's VaxzevriaTM for the first dose

Exclusion Criteria:

* Minors
* Pregnant or breastfeeding women
* Persons under tutorship or curatorship
* Protected adults
* Person under legal protection
* Person not affiliated to a social security scheme
* People with a contraindication to receiving the ComirnatyTM vaccine
* People who have already been vaccinated against SARS-CoV-2

Note: a history of COVID-19 (\> at 3 months) is not a contraindication to vaccination and is therefore not a criterion for non-inclusion in the study.

Primary outcomes:
measure: Protective humoral response after vaccination
timeFrame: Month 2
Secondary outcomes:
measure: Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 0
measure: Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 1
measure: Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 2
measure: Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 3
measure: Mucosal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 6
measure: Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 0
measure: Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 1
measure: Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 2
measure: Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 3
measure: Serum and nasal neutralization capacity against wild-type and emerging variants of concern (VOC)
timeFrame: Month 6
measure: Clinical protection after vaccination
timeFrame: Month 0
measure: Clinical protection after vaccination
timeFrame: Month 1
measure: Clinical protection after vaccination
timeFrame: Month 2
measure: Clinical protection after vaccination
timeFrame: Month 3
measure: Clinical protection after vaccination
timeFrame: Month 6
Other outcomes:
Locations:
city: Orléans
country: France
facility: CHR d'Orleans - Service Maladies Infectieuses
Study officials:
affiliation: CHR d'Orléans
name: Aymeric SEVE, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grzelak L, Temmam S, Planchais C, Demeret C, Tondeur L, Huon C, Guivel-Benhassine F, Staropoli I, Chazal M, Dufloo J, Planas D, Buchrieser J, Rajah MM, Robinot R, Porrot F, Albert M, Chen KY, Crescenzo-Chaigne B, Donati F, Anna F, Souque P, Gransagne M, Bellalou J, Nowakowski M, Backovic M, Bouadma L, Le Fevre L, Le Hingrat Q, Descamps D, Pourbaix A, Laouenan C, Ghosn J, Yazdanpanah Y, Besombes C, Jolly N, Pellerin-Fernandes S, Cheny O, Ungeheuer MN, Mellon G, Morel P, Rolland S, Rey FA, Behillil S, Enouf V, Lemaitre A, Creach MA, Petres S, Escriou N, Charneau P, Fontanet A, Hoen B, Bruel T, Eloit M, Mouquet H, Schwartz O, van der Werf S. A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations. Sci Transl Med. 2020 Sep 2;12(559):eabc3103. doi: 10.1126/scitranslmed.abc3103. Epub 2020 Aug 17.
citation: Planas D, Bruel T, Grzelak L, Guivel-Benhassine F, Staropoli I, Porrot F, Planchais C, Buchrieser J, Rajah MM, Bishop E, Albert M, Donati F, Prot M, Behillil S, Enouf V, Maquart M, Smati-Lafarge M, Varon E, Schortgen F, Yahyaoui L, Gonzalez M, De Seze J, Pere H, Veyer D, Seve A, Simon-Loriere E, Fafi-Kremer S, Stefic K, Mouquet H, Hocqueloux L, van der Werf S, Prazuck T, Schwartz O. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021 May;27(5):917-924. doi: 10.1038/s41591-021-01318-5. Epub 2021 Mar 26.