Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial.

BACKGROUND: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. METHODS: Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. DISCUSSION: This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. TRIAL REGISTRATION: ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.

Immune response to rabies post-exposure prophylaxis in patients with non-HIV secondary immunodeficiencies.

BACKGROUND: This study sought to determine the proportion of individuals with non-HIV secondary immunodeficiencies presenting inadequate antibody titers after rabies post-exposure prophylaxis (PEP) and to identify variables associated with inadequate response. METHODS: A retrospective review of the records of immunocompromised patients having received a full course of PEP after a rabies exposure and having been tested for post-PPE antibody titers in two French Antirabies Clinics, between 2013 and 2018, was conducted. Antibody titers < 0.5 EU/ml (ELISA) were classified as inadequate. RESULTS: A total of 28 individuals were included, 6 had inadequate post-PPE titers. None of the tested variable was independently associated with inadequate titers. CONCLUSIONS: Inadequate response was unpredictable and not explained either by the characteristics of patients or by the PEP regimen they received. These findings support the WHO recommendation to systematically assess post-PEP response in immunocompromised patients to detect non-responders, who might require an additional dose.

Characteristics of B-cell lymphomas in HIV/HCV-coinfected patients during the combined antiretroviral therapy era: an ANRS CO16 LYMPHOVIR cohort study.

Hepatitis C virus (HCV) infection is frequent among HIV-infected patients. We describe, the characteristics of 6 HIV/HCV-coinfected patients with B-cell non-Hodgkin lymphoma (NHL) included in a prospective cohort study of HIV-related lymphomas. Five of the 6 cases had features of marginal zone/lymphoplasmacytic NHL versus 1 of 33 HIV only-infected patients. Remarkably, anti-HCV treatment led to a hematological response in a patient with splenic marginal zone lymphoma. This supports the role of chronic antigenic stimulation by HCV on lymphomagenesis and further evaluation of HCV antiviral therapy in coinfected patients with NHL.