Title
Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia
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
Phase
Phase 2Lead Sponsor
University of NantesStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
SARS VirusIntervention/Treatment
XAV-19 ...Study Participants
416Early 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.
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.
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
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
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
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
Phase 2a: Inclusion Criteria: 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 WOCBP must have a negative urinary pregnancy test the day of inclusion 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 Exclusion Criteria: 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 Phase 2b: Inclusion criteria: Willing and able to provide written informed consent prior to performing study procedures Male or female ≥ 18 years Hospitalized for COVID-19 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 Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chestimaging [Chest X-ray or computed tomography]) Requiring O2 supplement ≤ 6L/min at screening Requiring O2 supplementation with SpO2 ≥ 92% on O2 therapy at screening (or ≥ 90 % if chronic obstructive pulmonary disease) 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) WOCBP must have a negative urinary pregnancy test the day of inclusion 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 Exclusion criteria: 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 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 Patient already included Prior hospitalisation in intensive care unit for the current covid-19 episode
