TIXAGEVIMAB/CILGAVIMAB Protection of Covid-19 in Transplanted Patients (TIXCI-TRANS)

TIXAGEVIMAB/CILGAVIMAB for Covid-19 Pre-exposition Prophylaxis in Solid Organ Transplanted Recipients

Covid-19 has a very bad prognosis in solid organ transplant recipients with a 60 days-mortality exceeding 20%. For this reason, transplant patients were prioritized to receive Covid-19 vaccination since December 2020 in France. Unfortunately, the vaccine response of these patients is insufficient after a standard vaccine regimen including 2 doses of mRNA (messenger ribonucleic acid) vaccine with a 50% seroconversion rate in many cohorts. As a result, on the advice of the "Conseil National d'Orientation Vaccinale", the French Health Authorities has authorized physicians to offer a 3rd dose of vaccine to organ transplant patients since April 11, 2021. The subsequent studies showed that half of the patients who did not seroconvert after the 2nd dose did develop a vaccine response after the third dose. For patients who do not respond after the 3rd dose, the clinicians are now allowed to offer a 4th dose of vaccine.

Unfortunately, approximately 25% of patients still remain non-responders to this 3- or 4-doses vaccine regimen. In addition, transplant recipients who do not developed a vaccine response after the 3rd dose are very unlikely to respond after the 4th dose. For patients who do not respond to the vaccination, the French Health Authorities had authorized the infusion of SARS Cov2 (Severe Acute Respiratory Syndrome Coronavirus 2) monoclonal antibodies as a pre-exposition prophylaxis in immunocompromised patients.

The value of using the TIXAGEVIMAB/CILGAVIMAB monoclonal antibody cocktail as primary prophylaxis has been demonstrated in the general population but this study did not include immunocompromised patients.

Here, the investigators propose to study the pharmacokinetics of TIXAGEVIMAB/CILGAVIMAB given in a pre-exposition prophylaxis scheme in non-responder solid organ transplanted patients after an adapted vaccinal scheme (i.e. 3 doses or more of mRNA vaccines).

Study Overview

• Status: Withdrawn
• Conditions: Solid Organ Transplant Recipients
• Intervention / Treatment: Biological: Blood and saliva samplings

• Study Type: Observational

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69437
    • Service de Néphrologie, Transplantation et Immunologie Clinique Hôpital Edouard Herriot - Hospices Civils de Lyon
  • Strasbourg, France, 67091
    • Service de Néphrologie et Transplantation, Hôpitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

160 solid organ transplant patients will be enrolled in the study. Recruitment will be performed among transplant patients at the two transplant centers participating in the study during a follow-up visit, after receipt of their serology results.

Patients will be allocated into two groups:

• Group 1 (100 patients): naïve patients, who have never received anti-SARS CoV2 monoclonal antibodies.
• Group 2 (60 patients): patients who have previously received anti-SARS Cov2 monoclonal antibodies.

Description

Inclusion Criteria:

• Male or female, 18 years of age or older
• Recipient of a solid organ transplant
• Subject affiliated with a health insurance company
• Patient able to understand the objectives and risks of the research and to give a non-objection
• Patient with a post-vaccination anti-Spike IgG (or RBD - Receptor Blinding Domain) titer of less than 30 BAU/ml ( (binding antibody units) measured at least 14 days after completion of an intensified vaccination regimen (at least 3 doses of mRNA vaccine) and prior to administration of anti-SARS-Cov-2 monoclonal antibodies.
• Group 1 criteria: Naïve patients, never having received anti-SARS CoV2 monoclonal antibodies.
• Group 2 criteria: Patients who have previously received anti-SARS Cov2 monoclonal antibodies

Exclusion Criteria:

• History of anaphylactic shock or known allergy to TIXAGEVIMAB/CILGAVIMAB
• Known history of Covid-19 or positive Covid-19 serology within 3 months prior to inclusion
• History of myocardial infarction or coronary artery disease within 3 months prior to inclusion
• Contraindication to an intramuscular injection
• Impossibility to give to the subject an informed information
• Subject under legal protection, guardianship or curatorship
• Plasmapheresis in progress or planned
• Weight less than 48 kg
• Patient participating in another interventional research study in progress
• Pregnant, parturient, or breastfeeding women

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Naïve patients; This study involve non-responder solid organ transplanted patients after an adapted vaccinal scheme (i.e. 3 doses or more of mRNA vaccines). Patients included in Group 1 are naïve patients; there have never received anti-SARS Cov2 monoclonal antibodies. They will have additional blood and saliva samplings during their study visits, which are included in their usual medical follow-up.	Biological: Blood and saliva samplings; At each protocol visits, on the occasion of a care collection, additional blood and saliva samples will be taken specifically for the study, with a total volume of blood of 38 mL, and a saliva sample of 1.5 to 2 mL per visit (inclusion, month 1, month 4, month 6, month 9 and month 12), corresponding to routine care.
Switched patients; This study involve non-responder solid organ transplanted patients after an adapted vaccinal scheme (i.e. 3 doses or more of mRNA vaccines). Patients included in Group 2 have previously received anti-SARS Cov2 monoclonal antibodies. They will have additional blood and saliva samplings during their study visits, which are included in their usual medical follow-up.	Biological: Blood and saliva samplings; At each protocol visits, on the occasion of a care collection, additional blood and saliva samples will be taken specifically for the study, with a total volume of blood of 38 mL, and a saliva sample of 1.5 to 2 mL per visit (inclusion, month 1, month 4, month 6, month 9 and month 12), corresponding to routine care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients whose serum has viral neutralization capacity in vitro at M6 after TIXAGEVIMAB/CILGAVIMAB injection.	Viral neutralization capacity will be analyzed by performing in-vitro neutralization tests from blood samples of enrolled patients. Samples will be analyzed centrally by virology Laboratory of Strasbourg Hospital throughout the study.	At Month 6.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Olivier THAUNAT, MD-PhD, Service de Néphrologie, Transplantation et Immunologie Clinique Hôpital Edouard Herriot - Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: monoclonal antibody; protective level of SARS CoV2 antibodies; pharmacokinetic of anti-SARS CoV2 antibodies; SARS CoV2 infection; viral neutralization capacity; anti-Nucleocapsid IgG (Immunoglobulin G)
• Other Study ID Numbers: 69HCL21_1433; 2021-A03245-36 (Other Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No