Clinical trial NCT05982704: Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19
Official title: Study of the Efficacy of Viral Neutralizing Monoclonal Antibodies Tiksagevimab/Cilgavimab and Regdanvimab for Omicron Strain Dominance in Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Coronavirus Infections
Keywords: viral neutralizing monoclonal antibodies
Tixagevimab/Cilgavimab
Regdanvimab
Omicron strain
Lead sponsor: City Clinical Hospital No.52 of Moscow Healthcare Department
Sponsor class: OTHER
Collaborators: name: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
First posted: 2023-08-08
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

* Obtaining informed consent.
* Collection of medical history (including previous COVID-19 history + dates; COVID-19 vaccination information + dates and type of vaccine used; revaccination data; data about co-morbidities as risk factors, etc.).
* Anthropometric data (height and weight) and demographic data.
* Physical exam.
* Collection of data on concomitant therapy.
* Assessment of vital signs: measuring blood pressure, pulse and body temperature, pulse oximetry (SpO2) and respiratory rate.
* Evaluation of SARS-CoV-2 virus test (smear PCR).
* CT scan of the lungs.
* Clinical blood count.
* Biochemical blood count.
* Complete urinalysis.
* ECG.
* Pregnancy test.
* Verification of eligibility for inclusion/inclusion.
* Decision of inclusion or exclusion of the patient.

Core period visits (drug prescription):

Visit 1 (Day 0-1) The conduct of Visit 1 takes place only after the patient has signed an informed consent form and the doctor-researcher has checked whether the inclusion/inclusion criteria are met)

* Blood sampling to determine the level of antigen-specific antibodies to SARS-CoV-2 and viral neutralizing activity of patients' blood sera against different variants of SARS-CoV-2 virus before drug using
* Sampling (nasal and oropharyngeal mucosa swabs) for PCR research or sequencing and viral load analysis
* Injection of the testing drug
* Interviewing the patient about subjective symptoms.
* Assessment of vital signs (BP, pulse and body tº measurements, pulse oximetry (SpO2) and frequency of breathing.
* ADR registration.
* Blood sampling to determine the level of antigen-specific antibodies to SARS-CoV-2 and viral neutralizing activity of patients' sera against different variants of SARS-CoV-2 virus immediately after administration testing drugs (Tixaghevimab/cilgavimab or Regdanvimab).

Visit 2 (Day 4)

* Physical exam.
* Collection of data on concomitant therapy.
* Assessment of vital signs: blood pressure, pulse and body tº measurements, pulse oximetry (SpO2) and frequency of breathing.
* Clinical blood count.
* Biochemical blood count.
* Sampling (nasal and oropharyngeal swabs) for PCR screening or sequencing and viral load analysis
* Blood sampling to determine the level of antigen-specific antibodies to SARS-CoV-2 and viral neutralizing activity of patients' sera against different variants of SARS-CoV-2 virus immediately after administration of the testing drugs (Tixaghevimab/cilgavimab or Regdanvimab).
* ADR registration.

Procedures for an unscheduled safety visit In case of clinical or laboratory signs of adverse reactions associated with the testing drug, an unscheduled visit should be scheduled. In addition to the scheduled emergency procedures and/or examinations, information on the combination therapy and adverse events is collected at the visit.

Minimum list of procedures for an unscheduled visit:

* Interviewing the patient about subjective symptomatology.
* Assessment of vital signs (BP, pulse and body tº measurements), pulse oximetry (SpO2) and frequency of breathing.
* Clinical blood count (may be ordered by the examining physician)
* Biochemical blood count (may be ordered by the examining physician)
* Registration and evaluation of ADR. Reporting to pharmacovigilance authorities (Roszdravnadzor) and to the pharmacovigilance department of the marketing authorization holder.

After the patient monitoring procedure, the efficacy and safety endpoints of the study drugs will be evaluated.

The volume of patients included in the study was formed on the basis of available resources and laboratory test capabilities related to efficacy endpoints of the investigational drugs, as well as clinical experience on the prescription of investigational drugs in scientific publications on this topic. After estimating the distribution of the sample, in the case of a non-normal distribution will be used nonparametric statistical methods for data analysis in IBM SPSS Statistics V.22. Numeric variables Numerical variables will be presented as medians and interquartile ranges (IQRs). Quantitative variables will be compared using Mann-Whitney U test and/or one-way Kruskal-Wallis analysis of variance. Fisher's exact test or χ2-square test will be used for qualitative variables. For all tests, p-value \< 0,05 is considered statistically significant.

Eligibility criteria: 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-19.
* 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.

Primary outcomes:
measure: 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)
timeFrame: 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
measure: Viral load in nasopharyngeal swabs of patients by real-time PCR
timeFrame: On the first (0) day ; on the fourth day (4)
Secondary outcomes:
measure: Adverse drug reaction
timeFrame: 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
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital 52
Study officials:
References: