Clinical trial NCT05601167: Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population
Official title: Open Multicentre Study for Assessment of the Safety and Efficacy Against COVID-19 of the Drug JTBC00201 (PROMOMED RUS LLC, Russia) in the Adult Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: Nirmatrelvir/ritonavir
Skayvira
SARS-CoV-2
Lead sponsor: Promomed, LLC
Sponsor class: OTHER
Collaborators: name: Sponsor GmbH
First posted: 2022-11-01
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is open-labe randomized multicenter comparative Phase III study conducted in 11 medical facilities. The objective of the study is to evaluate efficacy and safety of the drug JTBC00201, tablets in the setting of pathogenetic and symptomatic therapy as compared to standard therapy in outpatients with COVID-19.

Detailed description: Upon signing the informed consent form and screening, 264 eligible outpatients with mild or moderate COVID-19 were randomized at a 1:1 ratio to receive either nirmatrelvir/ritonavir tablets, 300/100 mg, 2 times a day with 12 ±2 hours interval for 5 days, or SOC

Eligibility criteria: Inclusion Criteria:

* Availability of PIS Informed Consent Form signed and dated by a patient.
* Male and female subjects aged 18 to 80 inclusive as of the time of signing the PIS Informed Consent Form.
* Confirmed COVID-19 at screening stage: positive for SARS-CoV-2 RNA laboratory test with nucleic acid amplification techniques (NAAT) or SARS-CoV-2 antigen with immunochromatographic assay.
* SARS-CoV-2 test results obtained up to 5 days prior to randomization may be taken into account upon availability of supporting documentation.
* Mild or moderate SARS-CoV-2 induced infection.
* At least one of the following COVID-19 symptoms as of the time of screening and randomization: nasal congestion or rhinitis; sore throat; dyspnoea or respiratory distress on exertion; cough; tiredness; pain in muscles or throughout the body; headache; chills; fever (body temperature \> 38 ⁰С); nausea; vomiting; diarrhoea; anosmia; ageusia.
* Disease onset (first symptom) within not more than 5 days prior to randomization
* The patient agrees and is able to take oral drug products.
* Patient's consent to use reliable contraception methods during the entire study and for 3 weeks after the end of the study. Reliable contraception methods are: sexual abstinence, the use of a condom combined with a spermicidal agent.
* Female subjects incapable of bearing children (history: hysterectomy, tubal ligation, infertility, menopause for more than 2 years), as well as male subjects with infertility or a history of vasectomy may participate in the study.

Exclusion Criteria:

* Hypersensitivity to the study drug components.
* Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
* Use of direct-acting antiviral drugs within 10 days prior to screening.
* The use of drugs at the time of screening whose clearance is highly dependent on the CYP3A isoenzyme, or which are strong inducers of CYP3A (for more information, see the section "Unauthorized pharmaceuticals").
* Necessity to use unauthorized pharmaceuticals.
* The need for oxygen therapy at the time of screening.
* Hospitalization required at time of screening, or hospitalization expected to be required for COVID-19 within 48 hours of randomization, excluding hospitalization to the observation facility for social reasons (e. g., living in a hostel, cohabiting with people, including those with risk factors for aggravated COVID-19, who, after contact with the patient, have a negative result for the SARS-CoV-2 RNA/antigen, etc.).
* Severe and extremely severe disease signs as of the time of screening.
* Vaccination within less than 4 weeks prior to screening.
* Possible or confirmed moderate COVID-19 within 6 months prior to screening.
* Possible or confirmed history of severe or very severe COVID-19.
* Patients with moderate to severe renal insufficiency (estimated glomerular filtration rate (GFR) \< 60 ml/min/1.73 m2 per CKD-EPI formula) or receiving renal replacement therapy at the time of screening.
* Severe liver failure (class C per Child-Pugh) at the time of screening or elevated ALT and/or AST levels of ≥ 2.5 UNL and/or elevated total bilirubin levels of ≥ 2 UNL (≥ 3 UNL with Gilbert's syndrome) in past medical history (within 6 months prior to screening).
* Positive test result for HIV, syphilis, hepatitis B and/or C at the time of screening.
* Alcohol, pharmacological and/or drug dependence (history and/or at the time of screening).
* Schizophrenia, schizoaffective disorder, bipolar disorder, or other psychiatric disorder (history or suspected) at the time of screening.
* Any history data that may complicate, in the opinion of the investigator, interpretation of the study results or create additional risk for the patient due to his/her participation in the study.
* Unwillingness or inability of a patient to comply with the Protocol procedures (in the opinion of the investigator).
* Pregnant or lactating women, or women planning a pregnancy.
* Participation in another clinical study within 3 months prior to enrolment in the present study.
* Other conditions that prevent the patient from inclusion in the study.

Primary outcomes:
measure: Prevalence of patients with COVID-19 severity increase as compared from baseline to Visit 4
timeFrame: From baseline to Visit 4 (days 14-15)
Secondary outcomes:
measure: Clinical status changes according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead)
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15), 5 (days 21±1), 6 (study completion, day 28±1)
measure: Clinical status deterioration incidence according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead) by ≥ 1 category
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)
measure: Achievement of clinical status 0 according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead)
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)
measure: Prevalence of patients with negative SARS-CoV-2 RNA test
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)
measure: Symptoms intensity score as per COVID-19 Related Symptom Scale
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15), 5 (days 21±1), 6 (study completion, day 28±1)
Other outcomes:
Locations:
city: Ivanovo
country: Russian Federation
facility: Regional Budgetary Healthcare Institution "Ivanovo Clinical Hospital"
city: Kirov
country: Russian Federation
facility: Kirov State Medical University of Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution City Clinical Hospital named after S. I. Spasokukotskiy of Moscow Healthcare Department
city: Ryazan'
country: Russian Federation
facility: Regional Clinic Hospital of Ryazan
city: Ryazan'
country: Russian Federation
facility: Ryazan State Medical University named after academician I.P. Pavlov of Ministry of Health of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Avrora MedFort, LLC
city: Saint Petersburg
country: Russian Federation
facility: OrCli Hospital, LLC
city: Saransk
country: Russian Federation
facility: Ogarev Mordova State University of Ministry of Health of the Russian Federation
city: Smolensk
country: Russian Federation
facility: Regional State Budgetary Healthcare Institution "Clinical Hospital No. 1"
city: Smolensk
country: Russian Federation
facility: Smolensk State Medical University of Ministry of Health of the Russian Federation
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Yaroslavl Oblast "Clinical Hospital No.3"
Study officials:
affiliation: Moscow State Clinical Hospital №50
name: Dmitriy Pushkar, Academician
role: PRINCIPAL_INVESTIGATOR
References:
citation: L.A. Balykova, N.M. Selezneva, E.I. Gorshenina, O.I. Shepeleva, N.V. Kirichenko, E.N. Simakina, K.B. Kolontarev, D.Yu. Pushkar, D.N. Zemskov, K.Ya. Zaslavskaya, S.M. Noskov, A.V. Taganov, P.A. Bely. modern directed antiviral COVID-19 therapy: results of multicenter clinical effectiveness and safety study of fixed nirmatrelvir+ritonavir combination. Pharmacy & Pharmacology. 2022;10(4):. DOI: 10.19163/2307-9266- 2022-10-4-