Efficacy and Safety of All-Oral Combination of Narlaprevir/Ritonavir and Sofosbuvir in Treatment-naïve Patients With Chronic Hepatitis C Genotype 1

NCT04246723 | Completed Phase 2 DMC

• 1 other identifier: CJ05013053
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 5

Brief Summary

Multicenter, open-label, phase II safety and efficacy study of all-oral combination of narlaprevir/ritonavir and sofosbuvir in Treatment-naïve Patients with Chronic Hepatitis C Genotype 1.

Conditions

Chronic Hepatitis c Genotype 1

Keywords

hepatitis; HCV; antiviral

Outcome Measures

Primary Outcomes (1)

• The proportion of patients achieved Sustained Virologic Response (SVR12) in treatment-naïve patients cohort, received study therapy during 12 weeks.

  SVR12 - Undetectable HCV ( Hepatitis C Virus) RNA ( Ribonucleic Acid) by Lower limit Of Detection (LOD) 12 weeks following the end of treatment. LOD for HCV RNA \<15 IU/mL

  Week 12 of follow-up period (SVR12) - week 24 of the study

Secondary Outcomes (5)

• The proportion of patients who achieved the Sustained Virological Response 24 weeks after the end of treatment (SVR24) in 12-week cohort

  24 weeks after the end of the treatment or week 36 of the study

• The proportion of patients achieved the End of treatment response (ETR) by LOD

  Baseline and week 12 of the study (cohort A) or week 8 of the study (cohort B)

• The proportion of patients who achieved the Sustained Virological Response 4 weeks after the end of treatment (SVR4) by LOD

  4 weeks after the end of treatment - week 16 of the study for cohort A and week 12 of the study for cohort B

• The proportion of patients received 12 weeks of study treatment who developed viral breakthrough

  week 12 of the study

• The proportion of patients received 12 weeks of study treatment who developed relapse

  week 12 of the study and week 24 of the study

Other Outcomes (6)

• The proportion of treatment-naïve patients received 8 weeks of study treatment who achieve the SVR 12 by LOD

  week 20 of the study

• The proportion of patients received 8 weeks of study treatment who achieved SVR24 by LOD

  week 32 of the study

• The proportion of treatment-naïve patients received 8 weeks of study treatment achieved the ETR by LOD

  Baseline and week 8 of the study (cohort B)

Study Arms (2)

Cohort A (Narlaprevir + Ritonavir + Sofosbuvir for 12 weeks)

EXPERIMENTAL

All of enrolled patients receive equal study therapy with Narlaprevir 200 mg Once a day (QD)/Ritonavir 100 mg QD/Sofosbuvir 400 mg QD orally for 12 weeks. Narlaprevir should be taken with ritonavir and food and should be taken at approximately the same morning time each day. Sofosbuvir can be taken with or without meals.

Drug: Narlaprevir; Drug: Ritonavir; Drug: Sofosbuvir

Cohort B (Narlaprevir + Ritonavir + Sofosbuvir for 8 weeks)

EXPERIMENTAL

All of enrolled patients receive equal study therapy with Narlaprevir 200 mg QD (once daily)/Ritonavir 100 mg QD/Sofosbuvir 400 mg QD orally for 8 weeks. Narlaprevir should be taken with ritonavir and food and should be taken at approximately the same morning time each day. Sofosbuvir can be taken with or without meals.

Drug: Narlaprevir; Drug: Ritonavir; Drug: Sofosbuvir

Interventions

Narlaprevir DRUG

100 mg oval shaped, concave, yellow film-coated tablets taken as 200 mg per os once daily. 28 tabs/36 tabs/ 56 tabs in bottle.

Cohort A (Narlaprevir + Ritonavir + Sofosbuvir for 12 weeks); Cohort B (Narlaprevir + Ritonavir + Sofosbuvir for 8 weeks)

Ritonavir DRUG

100 mg tablets taken as 100 mg per os once daily. 30 tablets in bottle

Cohort A (Narlaprevir + Ritonavir + Sofosbuvir for 12 weeks); Cohort B (Narlaprevir + Ritonavir + Sofosbuvir for 8 weeks)

Sofosbuvir DRUG

400 mg yellow, capsule-shaped film-coated tablets debossed with "GSI" on one side and "7977" on the other side, taken as 400 mg per os once daily. 28 tablets in bottle.

Cohort A (Narlaprevir + Ritonavir + Sofosbuvir for 12 weeks); Cohort B (Narlaprevir + Ritonavir + Sofosbuvir for 8 weeks)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are willing and able to provide written informed consent.
• Have confirmed chronic HCV infection as documented by:
• positive anti-HCV antibody (Ab) test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit
• Have HCV genotype 1 at screening as determined by the Central Laboratory. Any nondefinitive results must exclude the subject from study participation.
• Minimum HCV-RNA level of ≥ 10,000 IU at baseline;
• Treatment-naive patients to be enrolled into 8 week cohort must have HCV-RNA level \<1,000,000 IU/L at baseline;
• No evidence of cirrhosis; availability at Baseline of at least one of the following tests negative results:
• Liver biopsy within 2 years of screening showing absence of cirrhosis
• Fibroscan® with a result of ≤ 12.5 kilopascal (kPa) within 6 months of baseline/Day1
• FibroTest® score of ≤ 0.48 AND Aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI) of ≤ 1 performed during screening
• In the absence of a definitive diagnosis of the presence or absence of cirrhosis by the above criteria, a liver biopsy was required. Liver biopsy results supersede the results obtained by Fibroscan® or FibroTest®
• Have a screening electrocardiogram (ECG) without clinically significant abnormalities (P wave \< 0.1 s; PQ interval 0,12-0,2 s; QRS complex 0,06-0,1 s; QT interval 0,35-0,49 s).
• Must have the following laboratory parameters at screening:
• alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)
• AST ≤ 10 x ULN

You may not qualify if:

• Had prior exposure to Interferon (IFN), ribavirin (RBV), or other approved or experimental Direct-acting Antivirals (DAA) targeting the HCV.
• Had prior exposure to amiodarone within 24 months before the screening
• Are pregnant or nursing female or male with pregnant female partner.
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, cholangitis).
• Are infected with hepatitis B virus (HBV) or human immunodeficiency virus(HIV).
• Have history of malignancy diagnosed or treated within 5 years; subjects under evaluation for malignancy are not eligible.
• Have chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent \> 10 mg/day).
• Have clinically relevant drug or alcohol abuse within 12 months of screening. A positive drug screen must exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator.
• Have excessive alcohol consumption, defined as more than 3 drinks on any single day and more than 7 drinks per week for females, and \> than 4 drinks on any single day and more than 14 drinks per week for males.
• Have history of solid organ transplantation.
• Have history of clinically significant illness or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol by Investigators' opinion.
• Have history of a gastrointestinal disorder (or postoperative condition) that can interfere with the absorption of the study drug.
• Have history of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Usage of any prohibited concomitant medications as described in the protocol (Appendix 1 - list of drugs with expected drug-drug interactions due to concomitant ritonavir usage)
• Have known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients.

Sponsors & Collaborators

• R-Pharm: lead
• Almedis: collaborator
• Scientific Center EFiS: collaborator
• ChromSystemsLab: collaborator

Study Sites (5)

FBIS CSRI of Epidemiology of Federal Service on Customers

Moscow, 111123, Russia

Location

FSIS FRC of food and biotechnology

Moscow, 115446, Russia

Location

SBEI HPE MSMDU n.a. A.I. Evdokimov of Ministry of Health of Russia

Moscow, 125367, Russia

Location

FSBI HEI HPE Military Medical Academy n.a. S.M. Kirov

Saint Petersburg, 193163, Russia

Location

SPb SBIH Center on preventiomn and treatment of AIDS and infectional deseases

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Hepatitis

Interventions

narlaprevir; Ritonavir; Sofosbuvir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 29, 2020
• Study Start: May 6, 2019
• Primary Completion: April 8, 2020
• Study Completion: August 12, 2020
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

RU (5)