Study of the Efficacy of Viral Neutralizing Monoclonal Antibodies Tiksagevimab/Cilgavimab and Regdanvimab for Omicron Strain Dominance in Patients With COVID-19
Trial Snapshot
- Phase
- Phase 4
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 82
- Locations
- 1
- Primary Endpoint
- Viral neutralizing activity of patients' blood serum against different variants of SARS-CoV-2 virus (Wuhan and Omicron/ sublines BA.1, BA.2, BA.5)
Study Overview
Brief Summary
Study hypothesis: the viral neutralizing monoclonal antibodies Tiksagevimab/Cilgavimab and Regdanvimab have high neutralizing activity against SARS-CoV-2 coronavirus, including Omicron strain, and may be effective in treating patients with moderate to severe COVID-19.
Description of the clinical study: Administration of monoclonal antibodies as antiviral therapy to patients with covid-19 and further Assesment of viral neutralizing monoclonal antibodies (Tiksagevimab/Cilgavimab and Regdanvimab) efficacy for treatment of new coronavirus infection (COVID-19) in adult patients. Participation of patients of both sexes aged 18 years or older with COVID-19 of moderate to severe course, hospitalized. Inclusion of 82 patients in the study: 38 in the tixagevimab/cilgavimab group (at a dose of 150+150 mg), 24 patients in the regdanvimab group (at a dose of 40 mg/kg body weight) and 20 patients in the tixagevimab/cilgavimab group (at a dose of 300+300 mg).
Detailed Description
Description of the intervention:
Hospitalized patients with moderate to severe coronavirus infection received three types of therapy: the tixagevimab/cilgavimab group (at a dose of 150+150 mg), the regdanvimab group (at a dose of 40 mg/kg body weight), and the tixagevimab/cilgavimab group (at a dose of 300+300 mg).
Further monitoring of the patient:
Screening period The screening period in the study begins with the signing of informed consent and lasts no longer than 24 hours (Visit 1, day 0) until the patient is included in the study (randomization).
Screening procedures:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient's signature of an informed consent form.
- •Men and women aged 18 years or older.
- •Confirmed diagnosis of new coronavirus infection COVID-
- •Appearance of COVID-19 symptoms within 7 days prior to study inclusion
- •Risk factors for COVID-19 progression and severity.
Exclusion Criteria
- •Patients with hypersensitivity to the active substance or other excipients (for the "Evusheld" product group: histidine, histidine hydrochloride monohydrate, sucrose, polysorbate 80, methionine; for the "Regkiron" product group: L-histidine, L-histidine monohydrate, polysorbate 80, L-arginine monohydrate)
- •Patients with a history of anaphylactic reactions to drugs of monoclonal antibody class.
- •Need for oxygen therapy at the time of study inclusion.
- •Pregnancy.
Arms & Interventions
tixagevimab/cilgavimab (Group 1)
tixagevimab/cilgavimab at a dose of 150+150 mg
Intervention: tixagevimab/cilgavimab 150+150 mg (Drug)
tixagevimab/cilgavimab (Group 2)
tixagevimab/cilgavimab at a dose of 300+300 mg
Intervention: tixagevimab/cilgavimab 300+300 mg (Drug)
regdanvimab group
regdanvimab at a dose of 40 mg/kg body weight
Intervention: regdanvimab (Drug)
Outcomes
Primary Outcomes
Viral neutralizing activity of patients' blood serum against different variants of SARS-CoV-2 virus (Wuhan and Omicron/ sublines BA.1, BA.2, BA.5)
Time Frame: On the first (0) day before the drug is administered; on the first day after the drug is administered; on the fourth day (4) after the drug is administered
Preparation of serum samples for viral neutralizing activity analysis and determination of the level of viral neutralizing antibodies. Blood serum samples were inactivated at 56°C for 30 minutes in a solid-state thermostat. The neutralization reaction was performed in the constant dose-virus-serum dilution variant. Serum dilutions in DMEM culture medium with 2% inactivated fetal bovine serum were prepared, then 50 µl of serum dilutions were mixed with 100 TCID50 of SARS-CoV-2 virus (50 µl), incubated for 1 hour at 37°C and added to Vero E6 cells. The cells were incubated at 37ºC in 5% CO2, after 96 hours the cytopathic effect of the virus on the cell culture was recorded visually by assessing the disruption of the cell monolayer. The highest dilution of the tested serum, at which the cytopathic effect was suppressed, was taken as the viral neutralizing activity titer of the serum under study.
Viral load in nasopharyngeal swabs of patients by real-time PCR
Time Frame: On the first (0) day ; on the fourth day (4)
Virus production, determination of infectious titer, and confirmation by PCR. Virus accumulation was performed in Vero E6 cells in DMEM medium with 2% inactivated FBS. The culture fluid containing the virus was aliquoted, frozen, and stored at -80C. The infectious virus titer was determined on Vero E6 cells by TCID50 determination. TCID50 titer was calculated using the Reed-Muench method.
Secondary Outcomes
- Adverse drug reaction(On the first day after the drug is administered; on the fourth day after the drug is administered; an unscheduled visit in event of an ADR)
Investigators
Daria Fomina
Allergologist-immunologist, Head of the c Center of Allergy and Immunology
City Clinical Hospital No.52 of Moscow Healthcare Department