Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia (POLYCOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04453384
Recruitment Status : Active, not recruiting
First Posted : July 1, 2020
Last Update Posted : July 21, 2021
Sponsor:
Collaborators:
BPIfrance
Xenothera SAS
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
SARS Virus Drug: XAV-19 Drug: Placebo Phase 2

Detailed Description:
For the first set of statistical analyses, to allow early reporting of primary and secondary endpoints at D15, the blind will be partially broken once all patients have completed Day 29. Except for statisticians, only the principal investigator and the scientific coordinator will have access to the full data set for the analysis of the primary and secondary endpoints up to day 29. The database will be partially locked (with all data up to day 29) as neither monitors nor investigators will be informed of the unblinding until the final data for day 60 is completed and the final database is locked.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 416 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Treatment arm

Administrations of XAV-19

  • Phase 2a: XAV-19 at 0.5 mg/kg at D1 and D5(Group 1) or at 2 mg/kg at D1 and D5 (Group 2), or at 2 mg/kg at D1 (groupe 3)
  • Phase 2b: Selected dose from Phase 2a : one administration at 2 mg/kg on day1
Drug: 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

Placebo Comparator: Placebo arm

same administration as treatment arm

  • Phase 2a: two administrations of placebo (day 1 and day 5) for Group 1 and 2, one administration of placebo on day 1 for Group 3
  • Phase 2b: one administration of placebo on day 1
Drug: Placebo
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




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Phase 2a: Supplemental oxygen [ Time Frame: Day 1 to Day 29 ]
    Duration of supplemental oxygen

  4. Phase 2a: Evaluation of Transfer to intensive care [ Time Frame: Day 1 to Day 29 ]
    Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen

  5. Phase 2a: Normalization of Fever [ Time Frame: Day 1 to Day 29 ]
    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

  6. Phase 2a: Biomarkers [ Time Frame: Day 1 to Day 29 ]
    Biomarkers : CRP, Ferritin

  7. Phase 2a: Hospital length of stay [ Time Frame: Day 1 to Day 29 ]
    Evaluation of Hospital length of stay

  8. 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

  9. Phase 2b: Clinical severity [ Time Frame: Day 3, Day 5, Day 8, Day15 and Day 29 ]
    a) National Early Warning Score (NEWS) assessed while hospitalized and on Day 15 and Day 29

  10. Phase 2b: Clinical severity [ Time Frame: Day 29 ]
    b) Clinical status using the 8-point ordinal scale assessed daily until Day 29

  11. Phase 2b: Clinical severity : Improvement of clinical and biological parameters [ Time Frame: Day15, and Day 29 ]
    c) Temperature and blood analysis between baseline and Day 15, and Day 29

  12. 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

  13. 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

  14. 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

  15. Phase 2b: Clinical severity : Transfer in ICU by Day 29 [ Time Frame: 29 Days ]
    g) Transfer in ICU

  16. Phase 2b: Clinical severity : Hospitalization [ Time Frame: 60 Days ]
    h) Hospital length of stay (in days)

  17. 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

  18. Phase 2b: Clinical severity : Thrombotic events [ Time Frame: 60 Days ]
    j) Thrombotic events (peripheral venous, pulmonary, arterial)

  19. Phase 2b: mortality [ Time Frame: 29 Days ]
    k) All cause mortality

  20. 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

  21. Phase 2b: safety of Study drug infusion [ Time Frame: 29 days and 60 days ]
    Study drug discontinuation or temporary suspension of infusion

  22. 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

  23. 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

  24. Phase 2b: safety : hypersensitivity reactions and infusion reactions [ Time Frame: 29 days and 60 days ]
    Incidence of hypersensitivity reactions and infusion reactions

  25. 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

  26. 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)

  27. 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)


Other Outcome Measures:
  1. 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

  2. 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:

    • Spike/ACE2 neutralizing antibody titers: D1 (pre-, post dose), D3, D5, D8, D15 and D29
    • Lymphocytes sub-population: D1, D3, D5, D8 and D15
    • Transcriptomic analyses: D1, D3, D5, D8 and D15
    • Cytokines: D1, D3, D5, D8 and D15

  3. 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 ]
    • to compare pharmacokinetic parameters in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19 (master phase 2b), in order to confirm that the exposure and variability are similar
    • to compare the effects of neutralizing antibodies use on virus-induced immune response on longitudinal follow-up, and targets for "immuno-monitoring"
    • to investigate the immunogenicity of COVID-19 during treatment with XAV19 in patients receiving a fixed dose of 150mg with patients receiving 2mg/Kg of XAV-19



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Phase 2a:

Inclusion Criteria:

  1. Willing and able to provide written informed consent prior to performing study procedures
  2. Male or female ≥ 18 years and ≤ 85 years
  3. Hospitalized for COVID-19
  4. Positive SARS-CoV-2 RT-PCR in any body specimen (nasopharynx, saliva, sputum) ≤ 10 days before enrolment
  5. Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chest-imaging [Chest X-ray or computed tomography])
  6. Requiring O2 supplement ≤ 6L/min at screening
  7. Requiring O2 supplementation with SpO2 ≥ 94% on O2 therapy at screening
  8. First onset of COVID-19 symptoms ≤ 10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist
  9. WOCBP must have a negative urinary pregnancy test the day of inclusion
  10. 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
  11. Patients with French social security

Exclusion Criteria:

  1. Evidence of multiorgan failure (severe COVID-19)
  2. Mechanically ventilated (including ECMO)
  3. Receipt of immunoglobulins or any blood products in the past 30 days
  4. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
  5. End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
  6. Child-Pugh C stage liver cirrhosis
  7. Decompensated cardiac insufficiency
  8. History of active drug abuse
  9. Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
  10. Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
  11. Current documented and uncontrolled bacterial infection.
  12. Prior severe (grade 3) allergic reactions to plasma transfusion
  13. Patient participating in another interventional clinical trial
  14. Life expectancy estimated to be less than 6 months
  15. Patient under guardianship or trusteeship

Phase 2b:

Inclusion criteria:

  1. Willing and able to provide written informed consent prior to performing study procedures
  2. Male or female ≥ 18 years
  3. Hospitalized for COVID-19
  4. 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
  5. Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chestimaging [Chest X-ray or computed tomography])
  6. Requiring O2 supplement ≤ 6L/min at screening
  7. Requiring O2 supplementation with SpO2 ≥ 92% on O2 therapy at screening (or ≥ 90

    % if chronic obstructive pulmonary disease)

  8. 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)
  9. WOCBP must have a negative urinary pregnancy test the day of inclusion
  10. 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
  11. Patients with French social security

Exclusion criteria:

  1. Evidence of multiorgan failure (severe COVID-19)
  2. Mechanically ventilated (including ECMO)
  3. Receipt of immunoglobulins or any blood products in the past 30 days
  4. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
  5. End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
  6. Child-Pugh C stage liver cirrhosis
  7. Decompensated cardiac insufficiency
  8. Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
  9. Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
  10. Current documented and uncontrolled bacterial infection.
  11. Prior severe (grade 3) allergic reactions to plasma transfusion
  12. Patient participating in another interventional clinical trial
  13. Life expectancy estimated to be less than 6 months
  14. Patient under guardianship or trusteeship
  15. Patient already included
  16. Prior hospitalisation in intensive care unit for the current covid-19 episode

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04453384


Locations
Show Show 34 study locations
Sponsors and Collaborators
Nantes University Hospital
BPIfrance
Xenothera SAS
Investigators
Layout table for investigator information
Principal Investigator: Benjamin Gaborit CHU Nantes
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT04453384    
Other Study ID Numbers: RC20_0230
First Posted: July 1, 2020    Key Record Dates
Last Update Posted: July 21, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nantes University Hospital:
SARS-Cov-2
COVID-19
Moderate
pneumonia
antibody
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Pneumonia
Respiratory Tract Infections
Infections
Pneumonia, Viral
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases