Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population

NCT05601167 | Completed Phase 3

• 1 other identifier: NR-012022
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 11

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.

Conditions

COVID-19

Keywords

Nirmatrelvir/ritonavir; Skayvira; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Prevalence of patients with COVID-19 severity increase as compared from baseline to Visit 4

  Patient severity score at screening and during treatment was determined as per сurrent clinical Guidelines

  From baseline to Visit 4 (days 14-15)

Secondary Outcomes (5)

• Clinical status changes according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead)

  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)

• Clinical status deterioration incidence according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead) by ≥ 1 category

  From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)

• Achievement of clinical status 0 according to the WHO Ordinal Scale ranges from 0 (uninfected) to 8 (dead)

  From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)

• Prevalence of patients with negative SARS-CoV-2 RNA test

  From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)

• Symptoms intensity score as per COVID-19 Related Symptom Scale

  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)

Study Arms (2)

JTBC00201 (nirmatrelvir/ritonavir, Skayvira)

EXPERIMENTAL

Group 1 (n=132) received the study drug nirmatrelvir/ritonavir, tablets 300/100 mg, 2 times a day with 12 ±2 hours interval for 5 days in the setting of pathogenetic and symptomatic therapy provided by Interim Guidelines for the prevention, diagnosis and treatment of COVID-19 validated of the time of the study

Drug: nirmatrelvir/ritonavir

Standard of care

ACTIVE COMPARATOR

Group 2 (n=132) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the Interim Guidelines for the prevention, diagnosis and treatment of COVID-19 validated of the time of the study

Drug: Standard of care

Interventions

nirmatrelvir/ritonavir DRUG

Tablets 300/100mg, 2 times a day with 12 ±2 hours interval for 5 days

Also known as: JTBC00201

JTBC00201 (nirmatrelvir/ritonavir, Skayvira)

Standard of care DRUG

The administration of 'Standard of care' drugs was done according to the regimen recommended in the 'COVID-19 TreatmentGuidelines' validated at the time of the study

Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Promomed, LLC: lead
• Sponsor GmbH: collaborator

Study Sites (11)

Regional Budgetary Healthcare Institution "Ivanovo Clinical Hospital"

Ivanovo, Russia

Location

Kirov State Medical University of Ministry of Health of the Russian Federation

Kirov, Russia

Location

State Budgetary Healthcare Institution City Clinical Hospital named after S. I. Spasokukotskiy of Moscow Healthcare Department

Moscow, Russia

Location

Regional Clinic Hospital of Ryazan

Ryazan, Russia

Location

Ryazan State Medical University named after academician I.P. Pavlov of Ministry of Health of the Russian Federation

Ryazan, Russia

Location

Avrora MedFort, LLC

Saint Petersburg, Russia

Location

OrCli Hospital, LLC

Saint Petersburg, Russia

Location

Ogarev Mordova State University of Ministry of Health of the Russian Federation

Saransk, Russia

Location

Regional State Budgetary Healthcare Institution "Clinical Hospital No. 1"

Smolensk, Russia

Location

Smolensk State Medical University of Ministry of Health of the Russian Federation

Smolensk, Russia

Location

State Budgetary Healthcare Institution of the Yaroslavl Oblast "Clinical Hospital No.3"

Yaroslavl, Russia

Location

Related Publications (1)

• 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-

  BACKGROUND

Related Links

• Cyberleninka is an open access scientific electronic library

MeSH Terms

Conditions

COVID-19

Interventions

nirmatrelvir and ritonavir drug combination; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Dmitriy Pushkar, Academician

  Moscow State Clinical Hospital №50

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 1, 2022
• Study Start: February 17, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

RU (11)