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

NCT04453384 | Completed Phase 2 DMC

• 1 other identifier: RC20_0230
• Study Type: interventional
• Target: 416
• Locations: 3 countries
• Sites: 34

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.

Conditions

SARS Virus

Keywords

SARS-Cov-2; COVID-19; Moderate; pneumonia; antibody

Outcome Measures

Primary Outcomes (3)

• Phase 2a: XAV-19 antibody titers

  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

  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.

  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 Outcomes (27)

• Phase 2a: Pharmacokinetic analysis

  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

  day 15

• Phase 2a: Supplemental oxygen

  Day 1 to Day 29

• Phase 2a: Evaluation of Transfer to intensive care

  Day 1 to Day 29

• Phase 2a: Normalization of Fever

  Day 1 to Day 29

Other Outcomes (3)

• Phase 2b : Pharmacokinetic Study

  Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29

• Phase 2b : Immunomonitoring Study

  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 :

  Day 1, Day 3, Day 5, Day 8, Day 15 and Day 29

Study Arms (2)

Treatment arm

EXPERIMENTAL

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

Placebo arm

PLACEBO COMPARATOR

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

Interventions

XAV-19 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

Treatment arm

Placebo 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• BPIfrance: collaborator
• Xenothera SAS: collaborator

Study Sites (34)

CHU Amiens Picardie

Amiens, France

Location

CHU Angers

Angers, France

Location

Hôpital Privé d'Antony

Antony, France

Location

CH Avignon

Avignon, France

Location

CH de la Côte Basque

Bayonne, France

Location

APHP - Hôpital Avicennes

Bobigny, France

Location

CHU Caen

Caen, France

Location

CH Métropole Savoie

Chambéry, France

Location

CH Colmar

Colmar, France

Location

CH Sud Francilien

Corbeil-Essonnes, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

CH de La Rochelle

La Rochelle, France

Location

CH Le Mans

Le Mans, France

Location

CHRU Lille

Lille, France

Location

CHU Limoges

Limoges, France

Location

Hospices Civils Lyon

Lyon, France

Location

CH de Mont de Marzan

Mont-de-Marsan, France

Location

GHR Mulhouse Sud-Alsace

Mulhouse, France

Location

CHU Nantes

Nantes, France

Location

CHU Nice

Nice, France

Location

CHU Nîmes

Nîmes, France

Location

CHR Orléans La Source

Orléans, France

Location

APHP - Hôpital Tenon

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

CH René Dubos

Pontoise, France

Location

CH Cornouaille

Quimper, France

Location

CHU Reims

Reims, France

Location

CHU Saint Etienne

Saint-Priest-en-Jarez, France

Location

CHU Strasbourg

Strasbourg, France

Location

Hôpital FOCH

Suresnes, France

Location

CHRU Nancy

Vandœuvre-lès-Nancy, France

Location

CH Bretagne Atlantique

Vannes, France

Location

CHU Martinique

Fort-de-France, Martinique

Location

CHU La Réunion

Saint-Pierre, Reunion

Location

Related Publications (4)

• 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.

  PMID: 36700518 DERIVED

• 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.

  PMID: 34473343 DERIVED

• 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.

  PMID: 34181475 DERIVED

• 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.

  PMID: 33750432 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19; Lymphoma, Follicular; Pneumonia

Interventions

XAV-19

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Benjamin Gaborit

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: July 1, 2020
• Study Start: September 1, 2020
• Primary Completion: May 21, 2021
• Study Completion: August 19, 2021
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1); RE (1); FR (32)