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

NCT ID: NCT04453384

Last Updated: 2022-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 416 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2021-08-19

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.

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.

Conditions

SARS Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

XAV-19

Intervention Type: DRUG

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 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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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

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. 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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BPIfrance

OTHER

Sponsor Role: collaborator

Xenothera SAS

INDUSTRY

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin Gaborit

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

CHU Amiens Picardie

Amiens, , France

CHU Angers

Angers, , France

Hôpital Privé d'Antony

Antony, , France

CH Avignon

Avignon, , France

CH de la Côte Basque

Bayonne, , France

APHP - Hôpital Avicennes

Bobigny, , France

CHU Caen

Caen, , France

CH Métropole Savoie

Chambéry, , France

CH Colmar

Colmar, , France

CH Sud Francilien

Corbeil-Essonnes, , France

CHD Vendée

La Roche-sur-Yon, , France

CH de La Rochelle

La Rochelle, , France

CH Le Mans

Le Mans, , France

CHRU Lille

Lille, , France

CHU Limoges

Limoges, , France

Hospices Civils Lyon

Lyon, , France

CH de Mont de Marzan

Mont-de-Marsan, , France

GHR Mulhouse Sud-Alsace

Mulhouse, , France

CHU Nantes

Nantes, , France

CHU Nice

Nice, , France

CHU Nîmes

Nîmes, , France

CHR Orléans La Source

Orléans, , France

APHP - Hôpital Tenon

Paris, , France

Hôpital Saint Antoine

Paris, , France

CH René Dubos

Pontoise, , France

CH Cornouaille

Quimper, , France

CHU Reims

Reims, , France

CHU Saint Etienne

Saint-Priest-en-Jarez, , France

CHU Strasbourg

Strasbourg, , France

Hôpital FOCH

Suresnes, , France

CHRU Nancy

Vandœuvre-lès-Nancy, , France

CH Bretagne Atlantique

Vannes, , France

CHU Martinique

Fort-de-France, , Martinique

CHU La Réunion

Saint-Pierre, , Reunion

Countries

France; Martinique; Reunion

References

Kimber C, Valk SJ, Chai KL, Piechotta V, Iannizzi C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Hyperimmune immunoglobulin for people with COVID-19. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD015167. doi: 10.1002/14651858.CD015167.pub2.

Reference Type: DERIVED

PMID: 36700518 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34181475 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33750432 (View on PubMed)

Other Identifiers

RC20_0230

Identifier Type: -

Identifier Source: org_study_id