- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04453384
Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia (POLYCOR)
A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia
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 blunt an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions1-3.
Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication in severe cases is observed, neutralising antibody treatment can be very interesting for patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected patients is therefore an interesting therapeutic option currently under evaluation. However, the difficulties of collecting plasma and its safety aspects are not adapted to many patients.
A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates and a First In Human study with another fully representative GH-pAb from Xenothera is ongoing in volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans.
The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1) to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19 induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when administered to patients with COVID-19 induced moderate pneumonia.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Amiens, France
- CHU Amiens Picardie
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Angers, France
- CHU Angers
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Antony, France
- Hôpital Privé d'Antony
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Avignon, France
- Ch Avignon
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Bayonne, France
- CH de la Cote Basque
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Bobigny, France
- APHP - Hôpital Avicennes
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Caen, France
- CHU Caen
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Chambéry, France
- CH Metropole Savoie
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Colmar, France
- CH Colmar
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Corbeil-Essonnes, France
- CH SUd Francilien
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La Roche-sur-Yon, France
- CHD Vendee
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La Rochelle, France
- CH de la Rochelle
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Le Mans, France
- CH Le Mans
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Lille, France
- CHRU Lille
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Limoges, France
- CHU Limoges
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Lyon, France
- Hospices Civils LYON
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Mont-de-Marsan, France
- CH de Mont de Marzan
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Mulhouse, France
- GHR Mulhouse Sud-Alsace
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Nantes, France
- CHU Nantes
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Nice, France
- CHU Nice
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Nîmes, France
- Chu Nimes
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Orléans, France
- CHR Orléans La Source
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Paris, France
- Hopital Saint Antoine
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Paris, France
- APHP - Hôpital Tenon
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Pontoise, France
- CH René Dubos
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Quimper, France
- Ch Cornouaille
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Reims, France
- CHU Reims
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Saint-Priest-en-Jarez, France
- CHU Saint Etienne
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Strasbourg, France
- CHU Strasbourg
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Suresnes, France
- Hopital FOCH
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Vandœuvre-lès-Nancy, France
- CHRU Nancy
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Vannes, France
- CH Bretagne Atlantique
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Fort de France, Martinique
- CHU Martinique
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Saint-Pierre, Réunion
- CHU La Réunion
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Phase 2a:
Inclusion Criteria:
- Willing and able to provide written informed consent prior to performing study procedures
- Male or female ≥ 18 years and ≤ 85 years
- Hospitalized for COVID-19
- Positive SARS-CoV-2 RT-PCR in any body specimen (nasopharynx, saliva, sputum) ≤ 10 days before enrolment
- Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chest-imaging [Chest X-ray or computed tomography])
- Requiring O2 supplement ≤ 6L/min at screening
- Requiring O2 supplementation with SpO2 ≥ 94% on O2 therapy at screening
- First onset of COVID-19 symptoms ≤ 10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist
- WOCBP must have a negative urinary pregnancy test the day of inclusion
- All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of XAV-19, whichever is longer
- Patients with French social security
Exclusion Criteria:
- Evidence of multiorgan failure (severe COVID-19)
- Mechanically ventilated (including ECMO)
- Receipt of immunoglobulins or any blood products in the past 30 days
- Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
- End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
- Child-Pugh C stage liver cirrhosis
- Decompensated cardiac insufficiency
- History of active drug abuse
- Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
- Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
- Current documented and uncontrolled bacterial infection.
- Prior severe (grade 3) allergic reactions to plasma transfusion
- Patient participating in another interventional clinical trial
- Life expectancy estimated to be less than 6 months
- Patient under guardianship or trusteeship
Phase 2b:
Inclusion criteria:
- Willing and able to provide written informed consent prior to performing study procedures
- Male or female ≥ 18 years
- Hospitalized for COVID-19
- Documentation of SARS-Cov-2 infection before enrolment, by positive SARS-CoV-2 RT-PCR or antigen in any body specimen (nasopharynx, oropharynx, saliva, sputum, bronchoalveolar lavage …) before enrolment
- Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chestimaging [Chest X-ray or computed tomography])
- Requiring O2 supplement ≤ 6L/min at screening
Requiring O2 supplementation with SpO2 ≥ 92% on O2 therapy at screening (or ≥ 90
% if chronic obstructive pulmonary disease)
- First onset of COVID-19 symptoms ≤ 14 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist (other symptoms such as asthenia not to be considered in this list)
- WOCBP must have a negative urinary pregnancy test the day of inclusion
- All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of XAV-19, whichever is longer
- Patients with French social security
Exclusion criteria:
- Evidence of multiorgan failure (severe COVID-19)
- Mechanically ventilated (including ECMO)
- Receipt of immunoglobulins or any blood products in the past 30 days
- Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
- End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
- Child-Pugh C stage liver cirrhosis
- Decompensated cardiac insufficiency
- Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
- Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
- Current documented and uncontrolled bacterial infection.
- Prior severe (grade 3) allergic reactions to plasma transfusion
- Patient participating in another interventional clinical trial
- Life expectancy estimated to be less than 6 months
- Patient under guardianship or trusteeship
- Patient already included
- Prior hospitalisation in intensive care unit for the current covid-19 episode
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment arm
Administrations of XAV-19
|
Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1
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PLACEBO_COMPARATOR: Placebo arm
same administration as treatment arm
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Phase 2a: Administration on Day 1 and day 5 for Group1 and 2, Administration on Day 1 for Group 3 Phase 2b: Administration on Day 1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 2a: XAV-19 antibody titers
Time Frame: Day 8
|
The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8
|
Day 8
|
Phase 2a: Adverse events of XAV-19
Time Frame: Day 29
|
Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days
|
Day 29
|
Phase 2b: To evaluate the efficacy of XAV-19 + standard-of-care (Soc) therapy compared with placebo + Soc therapy for treatment of COVID-19 assessed by the proportion of patients who die or develop respiratory failure between baseline and Day 15.
Time Frame: Day 15
|
Efficacy is defined by the proportion of patients who died or develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices, invasive mechanical ventilation (corresponding to a score of 5 or more on the WHO 8 point ordinal scale) or by an increase of the required O2 supplement (more or equals to 10 L/minutes with a non-rebreather mask (oxygen mask with reservoir bag)
|
Day 15
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 2a: Pharmacokinetic analysis
Time Frame: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29
|
XAV-19 Antibody titer over the time
|
Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29
|
Phase 2a: Antibody titer between the two groups
Time Frame: day 15
|
The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients
|
day 15
|
Phase 2a: Supplemental oxygen
Time Frame: Day 1 to Day 29
|
Duration of supplemental oxygen
|
Day 1 to Day 29
|
Phase 2a: Evaluation of Transfer to intensive care
Time Frame: Day 1 to Day 29
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Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen
|
Day 1 to Day 29
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Phase 2a: Normalization of Fever
Time Frame: Day 1 to Day 29
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Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1
|
Day 1 to Day 29
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Phase 2a: Biomarkers
Time Frame: Day 1 to Day 29
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Biomarkers : CRP, Ferritin
|
Day 1 to Day 29
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Phase 2a: Hospital length of stay
Time Frame: Day 1 to Day 29
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Evaluation of Hospital length of stay
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Day 1 to Day 29
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Phase 2b: Efficacy of XAV-19
Time Frame: Day 8 and Day 29
|
Proportion of patients who die, develop respiratory failure, as defined by the requirement of noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation at Day 8 and D29
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Day 8 and Day 29
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Phase 2b: Clinical severity
Time Frame: Day 3, Day 5, Day 8, Day15 and Day 29
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a) National Early Warning Score (NEWS) assessed while hospitalized and on Day 15 and Day 29
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Day 3, Day 5, Day 8, Day15 and Day 29
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Phase 2b: Clinical severity
Time Frame: Day 29
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b) Clinical status using the 8-point ordinal scale assessed daily until Day 29
|
Day 29
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Phase 2b: Clinical severity : Improvement of clinical and biological parameters
Time Frame: Day15, and Day 29
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c) Temperature and blood analysis between baseline and Day 15, and Day 29
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Day15, and Day 29
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Phase 2b: Clinical severity : Oxygenation
Time Frame: 29 Days
|
d) Days of oxygen therapy over 29 days PaO2 / FiO2 at baseline, Day 5, Day 8, Day 15, Day 29 if available
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29 Days
|
Phase 2b: Clinical severity : Non-invasive ventilation, high-flow oxygen
Time Frame: 29 Days
|
e) e) Days of non-invasive ventilation or high flow oxygen (if applicable) up to Day 29
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29 Days
|
Phase 2b: Clinical severity : Invasive mechanical ventilation / Extra Corporeal Membrane Oxygenation (ECMO)
Time Frame: 29 Days
|
f) Days of invasive mechanical ventilation/ECMO (if applicable) up to Day 29
|
29 Days
|
Phase 2b: Clinical severity : Transfer in ICU by Day 29
Time Frame: 29 Days
|
g) Transfer in ICU
|
29 Days
|
Phase 2b: Clinical severity : Hospitalization
Time Frame: 60 Days
|
h) Hospital length of stay (in days)
|
60 Days
|
Phase 2b: Clinical severity : Mortality
Time Frame: 60 Days
|
i) All-cause mortality evaluated between baseline and Day 15 and between baseline and at Day 29 and at Day 60
|
60 Days
|
Phase 2b: Clinical severity : Thrombotic events
Time Frame: 60 Days
|
j) Thrombotic events (peripheral venous, pulmonary, arterial)
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60 Days
|
Phase 2b: mortality
Time Frame: 29 Days
|
k) All cause mortality
|
29 Days
|
Phase 2b: safety
Time Frame: 29 days and 60 days
|
Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events
|
29 days and 60 days
|
Phase 2b: safety of Study drug infusion
Time Frame: 29 days and 60 days
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Study drug discontinuation or temporary suspension of infusion
|
29 days and 60 days
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Phase 2b: safety : study drug discontinuation
Time Frame: 29 days and 60 days
|
Proportion of participants with treatment emergent adverse events leading to study drug discontinuation
|
29 days and 60 days
|
Phase 2b: safety : major or opportunistic bacterial or fungal infections
Time Frame: 29 days and 60 days
|
Incidence of major or opportunistic bacterial or fungal infections
|
29 days and 60 days
|
Phase 2b: safety : hypersensitivity reactions and infusion reactions
Time Frame: 29 days and 60 days
|
Incidence of hypersensitivity reactions and infusion reactions
|
29 days and 60 days
|
Phase 2b: safety : biological parameters
Time Frame: 29 days and 60 days
|
White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D15 and D29
|
29 days and 60 days
|
Phase 2b: Exploratory analysis : qualitative and quantitative SARS-CoV-2 status
Time Frame: Day 1, Day 8, Day 15 and Day 29
|
SARS-CoV-2 status (positive or negative and quantitatively, including variant information by sequencing) over time (D1, D8, D15, and D29)
|
Day 1, Day 8, Day 15 and Day 29
|
Phase 2b: Exploratory analysis : SARS-CoV-2 status viral load
Time Frame: Day 1, Day 8, Day 15 and Day 29
|
SARS-CoV-2 status viral load over time (D1, D8, D15, and D29)
|
Day 1, Day 8, Day 15 and Day 29
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 2b : Pharmacokinetic Study
Time Frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
Pharmacokinetic analysis correspond to antibody titer measurements at Day 1 (pre-dose, post-dose), Day 3, Day 5, Day 8, Day 15, and Day 29
|
Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
Phase 2b : Immunomonitoring Study
Time Frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
The endpoints encompass the following analysis:
|
Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
Phase 2b : Terminal ancillary Study (20 additional patients receiving a fixed dose of 150mg of XAV-19 :
Time Frame: Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
|
Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Benjamin Gaborit, CHU Nantes
Publications and helpful links
General Publications
- Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- Gaborit B, Dailly E, Vanhove B, Josien R, Lacombe K, Dubee V, Ferre V, Brouard S, Ader F, Vibet MA, Le Thuaut A, Danger R, Flet L, Omnes A, Berly L, Chiffoleau A, Jobert A, Duvaux O, Raffi F; POLYCOR Trial Group. Pharmacokinetics and Safety of XAV-19, a Swine Glyco-humanized Polyclonal Anti-SARS-CoV-2 Antibody, for COVID-19-Related Moderate Pneumonia: a Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study. Antimicrob Agents Chemother. 2021 Aug 17;65(9):e0123721. doi: 10.1128/AAC.01237-21. Epub 2021 Aug 17.
- Gaborit B, Vanhove B, Vibet MA, Le Thuaut A, Lacombe K, Dubee V, Ader F, Ferre V, Vicaut E, Orain J, Le Bras M, Omnes A, Berly L, Jobert A, Morineau-Le Houssine P, Botturi K, Josien R, Flet L, Degauque N, Brouard S, Duvaux O, Poinas A, Raffi F; POLYCOR study group. 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. Trials. 2021 Mar 9;22(1):199. doi: 10.1186/s13063-021-05132-9.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- RC20_0230
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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