TIXAGEVIMAB/CILGAVIMAB Protection of Covid-19 in Transplanted Patients

NCT05234398 | Withdrawn

• 2 other identifiers: 69HCL21_14332021-A03245-36
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Solid Organ Transplant Recipients

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)

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (2)

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

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

Interventions

Blood and saliva samplings BIOLOGICAL

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.

Naïve patients; Switched patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• History of anaphylactic shock or known allergy to TIXAGEVIMAB/CILGAVIMAB
• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Service de Néphrologie, Transplantation et Immunologie Clinique Hôpital Edouard Herriot - Hospices Civils de Lyon

Lyon, 69437, France

Location

Service de Néphrologie et Transplantation, Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Olivier THAUNAT, MD-PhD

  Service de Néphrologie, Transplantation et Immunologie Clinique Hôpital Edouard Herriot - Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 10, 2022
• Study Start: February 1, 2022
• Primary Completion: February 1, 2023
• Study Completion: August 1, 2023
• Last Updated: September 1, 2022

Record last verified: 2022-08

Locations

FR (2)