Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of XAV-19 drug in patients with moderate-to-severe COVID-19.

Official Title
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An International, Placebo-controlled, Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of 150 mg XAV-19 Infusion, in Patients With Moderate to Severe COVID-19: the EUROXAV Study

Conditions
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COVID-19

Intervention / Treatment
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* Drug: XAV-19
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I1) Male or female patient aged 18 years or over, weighing >50 Kg and <120 Kg, at the time of signing the informed consent, I2) Patient presenting in a specialized or an emergency unit I3) Patient presenting signs of pneumonia evidenced by at least 1 of the following: auscultation, chest X-Ray, CT scan OR presenting COVID-19 related symptoms having started less than 10 days prior to screening visit, including at least 2 of the following: fever, cough, sore throat or nasal discharge, dyspnea (shortness of breath), thoracic pain, headache or fatigue, myalgia, anosmia, dysgeusia, diarrhea, nausea I4) Patient with SpO2 > 90% (at ambient air) I5) Patient with a first positive SARS-CoV-2 test (RT-PCR, RT-qPCR or antigen test) in the last 10 days or at screening I6) Women of childbearing potential (WOCBP) must have a negative urine pregnancy test at screening and use a highly effective birth control until 90 days after the administration of study drug I7) Non-vasectomized male patients having a female partner of childbearing potential must agree to use a highly effective method of contraception until 90 days after the administration of study drug, I8) Patient capable of giving signed informed consent. Exclusion Criteria: E1) Patient with a positive SARS CoV-2 test (RT-PCR, RT-qPCR or antigen test) of more than 10 days before the screening visit E2) Patient with multiorgan failure E3) Patient requiring immediate Intensive Care Unit (ICU) hospitalization E4) Patient participating in another clinical trial with an investigative agent E5) Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a phase II/III, multicenter, international, randomized (1:1), placebo-controlled, parallel group, double-blind study to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XAV-19<br>XAV-19 | Drug: XAV-19<br>* 150 mg of XAV-19 single IV perfusion<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an aggravation of COVID-19 | The aggravation is defined as a worsening of the score of at least 1 point on the WHO 7-point ordinal scale compared to the score on the WHO 7-point ordinal scale at randomization. | within 8 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical parameters : body temperature | °C | Between randomization and Day 3, 5, 8 and 15 | 
| Change in Clinical parameters : Respiratory rate | breath/min | Between randomization and Day 3, 5, 8 and 15 | 
| Change in Clinical parameters : SpO2 at ambiant air |  | Between randomization and Day 3, 5, 8 and 15 | 
| Change in Clinical parameters : Supplemental O2 | L/min | Between randomization and Day 3, 5, 8 and 15 | 
| Change in severity on Common Terminology Criteria of Adverse Events (CTCAE) scale (version 5.0) | Shortness of breath and thoracic pain Scale score : Dyspnea: grade 1 (shortness of breath with moderate exertion) to 5 (death) Non-cardiac chest pain: grade 1 (mild pain) to 3 (severe pain) | Between randomization and Day 3, 5, 8 and 15 | 
| Duration of patient's requirement in supplemental O2 | Time requiring supplemental O2 at Day 15 will be defined as the time in days from randomization to the date of requiring supplemental O2. | up to 15 days | 
| Duration of aggravation | Duration of aggravation will be defined as the time in days between start date of aggravation and improvement date. | up to 15 days | 
| Length of hospital stay |  | up to 15 days | 
| Viral status: RT-PCR or RT-qPCR for SARS-CoV-2 | (positive/negative) | At randomization and on Day 8 or at the end of follow-up, whichever comes first | 
| Proportion of patients referred to Intensive Care Unit (ICU) |  | Between randomization and Day 3, 5, 8 and 15 | 
| Proportion of patients with need for mechanical ventilation |  | At randomization and at Day 3, 5, 8 and 15 | 
| Survival rates |  | at day 8 and day 15 after randomization | 
| Safety: Occurrence of adverse effects | Number and Proportion of participants with AE, SAE and treatment emergent adverse events leading to study drug discontinuation, to concomitant or additional treatment | up to 15 days | 
| Safety: hypersensitivity or allergy | Incidence of hypersensitivity reactions and allergy | up to 15 days | 
| Safety: laboratories abnormalities : white blood cell count | G/L | up to 15 days | 
| Safety: laboratories abnormalities : red blood cell count | 10 12/L | up to 15 days | 
| Safety: laboratories abnormalities : hemoglobin | g/dL | up to 15 days | 
| Safety: laboratories abnormalities : platelets | G/L | up to 15 days | 
| Safety: laboratories abnormalities : creatinine | µmol/L | up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, polyclonal IgG