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

• Sponsor: Nantes University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT04453384
• Collaborator: BPIfrance (Other), Xenothera SAS (Industry)
• Enrollment: 416
• Locations: 34
• Arms: 2
• Actual Duration (Months): 11.6
• Patients Per Site: 12.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Sep 1, 2020
• Actual Primary Completion Date: May 21, 2021
• Actual Study Completion Date: Aug 19, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Phase 2a: XAV-19 antibody titers [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 [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. [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 [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 [day 15]

   The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients

3. Phase 2a: Supplemental oxygen [Day 1 to Day 29]

   Duration of supplemental oxygen

4. Phase 2a: Evaluation of Transfer to intensive care [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 [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 [Day 1 to Day 29]

   Biomarkers : CRP, Ferritin

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

   Evaluation of Hospital length of stay

8. Phase 2b: Efficacy of XAV-19 [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 [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 [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 [Day15, and Day 29]

    c) Temperature and blood analysis between baseline and Day 15, and Day 29

12. Phase 2b: Clinical severity : Oxygenation [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 [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) [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 [29 Days]

    g) Transfer in ICU

16. Phase 2b: Clinical severity : Hospitalization [60 Days]

    h) Hospital length of stay (in days)

17. Phase 2b: Clinical severity : Mortality [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 [60 Days]

    j) Thrombotic events (peripheral venous, pulmonary, arterial)

19. Phase 2b: mortality [29 Days]

    k) All cause mortality

20. Phase 2b: safety [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 [29 days and 60 days]

    Study drug discontinuation or temporary suspension of infusion

22. Phase 2b: safety : study drug discontinuation [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 [29 days and 60 days]

    Incidence of major or opportunistic bacterial or fungal infections

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

    Incidence of hypersensitivity reactions and infusion reactions

25. Phase 2b: safety : biological parameters [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 [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 [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 [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 [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 : [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

1. 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)

2. WOCBP must have a negative urinary pregnancy test the day of inclusion

3. 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

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Amiens Picardie	Amiens		France
2	CHU Angers	Angers		France
3	Hôpital Privé d'Antony	Antony		France
4	CH Avignon	Avignon		France
5	CH de la Côte Basque	Bayonne		France
6	APHP - Hôpital Avicennes	Bobigny		France
7	CHU Caen	Caen		France
8	CH Métropole Savoie	Chambéry		France
9	CH Colmar	Colmar		France
10	CH Sud Francilien	Corbeil-Essonnes		France
11	CHD Vendée	La Roche-sur-Yon		France
12	CH de La Rochelle	La Rochelle		France
13	CH Le Mans	Le Mans		France
14	CHRU Lille	Lille		France
15	CHU Limoges	Limoges		France
16	Hospices Civils Lyon	Lyon		France
17	CH de Mont de Marzan	Mont-de-Marsan		France
18	GHR Mulhouse Sud-Alsace	Mulhouse		France
19	CHU Nantes	Nantes		France
20	CHU Nice	Nice		France
21	CHU Nîmes	Nîmes		France
22	CHR Orléans La Source	Orléans		France
23	APHP - Hôpital Tenon	Paris		France
24	Hôpital Saint Antoine	Paris		France
25	CH René Dubos	Pontoise		France
26	CH Cornouaille	Quimper		France
27	CHU Reims	Reims		France
28	CHU Saint Etienne	Saint-Priest-en-Jarez		France
29	CHU Strasbourg	Strasbourg		France
30	Hôpital FOCH	Suresnes		France
31	CHRU Nancy	Vandœuvre-lès-Nancy		France
32	CH Bretagne Atlantique	Vannes		France
33	CHU Martinique	Fort de France		Martinique
34	CHU La Réunion	Saint-Pierre		Réunion

Sponsors and Collaborators

• Nantes University Hospital
• BPIfrance
• Xenothera SAS

Investigators

• Principal Investigator: Benjamin Gaborit, CHU Nantes

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nantes University Hospital
• ClinicalTrials.gov Identifier: NCT04453384
• Other Study ID Numbers: RC20_0230
• First Posted: Jul 1, 2020
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: COVID-19; Pneumonia

Study Results

No Results Posted as of Mar 25, 2022