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

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ClinicalTrials.gov Identifier: NCT04453384
Recruitment Status : Recruiting
First Posted : July 1, 2020
Last Update Posted : September 16, 2020
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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 368 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 : November 2020
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 (Group 1) or at 2 mg/kg (Group 2)
  • Phase 2b: Selected dose from Phase 2a
Drug: XAV-19
Administration on Day 1 and day 5

Placebo Comparator: Placebo arm

same administration as treatment arm

  • Phase 2a: two administrations of placebo on day 1 and day 5
  • Phase 2b: two administrations of placebo on day 1 and day 5
Drug: Placebo
Administration on Day 1 and day 5




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: Time to weaning of supplemental oxygen. [ Time Frame: Day 15 ]
    If patient is still on oxygen at Day 15 or if the patient is weaned but put back on oxygen then the delay will be censored at 15 days.


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 ]
    b) 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: National Early Warning Score (NEWS) [ Time Frame: Day 1 and Day 15 ]
    Evaluation of the National Early Warning Score at Day 15 and difference in NEWS between Day1 and Day15. The NEWS is graded from to 23 with an aggregated score between 0-4 being a low clinical risk and an aggregated score >7 being a hich clinical risk

  9. Phase 2b: clinical status [ Time Frame: Day 3, Day 5, Day 8, Day 11, Day15, and Day 29 ]
    Clinical status using the 7-point ordinal scale assessed

  10. Phase 2b: Time to improvement [ Time Frame: 29 Days ]
    Time to improvement of one category from admission using the 7-point ordinal scale. This scale is rated 0 to 7 with score 0 being the better score (no clinical impact) and 7 being the worst score (death)

  11. Phase 2b: fever normalization [ Time Frame: 29 Days ]
    d) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)

  12. Phase 2b: Oxygen therapy [ Time Frame: 29 Days ]
    Duration of oxygen therapy

  13. Phase 2b: oxygen requirement [ Time Frame: 29 Days ]
    Comparison of oxygen requirement between the two groups

  14. Phase 2b: Time to weaning [ Time Frame: Day 15 ]
    g) Time to weaning in supplemental oxygen and proportion without O2 requirement at D15, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)

  15. Phase 2b: Ventilation [ Time Frame: 29 Days ]
    h) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study

  16. Phase 2b: Hospital length of stay [ Time Frame: 29 Days ]
    Evaluation of hospital length of stay

  17. Phase 2b: mortality [ Time Frame: 29 Days ]
    All cause mortality

  18. Phase 2b: safety [ Time Frame: 29 Days ]
    • Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events
    • Proportion of participants with treatment emergent adverse events leading to study drug discontinuation
    • Incidence of major or opportunistic bacterial or fungal infections
    • Incidence of hypersensitivity reactions and infusion reactions
    • White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29
    • SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples
    • Time to RT-PCR virus negativity in nasopharyngeal swab samples



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.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. 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

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


Contacts
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Contact: Benjamin GABORIT +33 (0)2 44 76 82 92 benjamin.GABORIT@chu-nantes.fr

Locations
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France
CHU Angers Recruiting
Angers, France
Contact: Vincent DUBEE, MD, PhD         
Hospices Civils Lyon Not yet recruiting
Lyon, France
Contact: Florence ADER, MD, PhD         
CHU Nantes Recruiting
Nantes, France
Contact: Benjamin GABORIT, MD, PhD         
Principal Investigator: Benjamin GABORIT, MD, PhD         
Principal Investigator: François RAFFI, MD, PhD         
Hôpital Saint Antoine Recruiting
Paris, France
Contact: Karine LACOMBE, MD, PhD         
Sponsors and Collaborators
Nantes University Hospital
BPIfrance
Xenothera SAS
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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: September 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections