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

NCT03485846 | Completed Phase 2

• 1 other identifier: CJ05013046
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to confirm that combination of Narlaprevir, Ritonavir and Daclatasvir is safe and highly effective regimen in treatment-naїve patients with chronic hepatitis C (HCV) genotype 1b infection.

Conditions

Chronic Hepatitis C Genotype 1b

Keywords

hepatitis C; chronic; 1b genotype; oral treatment

Outcome Measures

Primary Outcomes (1)

• The proportion of patients achieved Sustained Virologic Response (SVR12)

  SVR12 - Undetectable HCV RNA by lower limit of detection (LOD) 12 weeks following the end of treatment

  Week 12 of follow-up period

Secondary Outcomes (5)

• The proportion of patients achieved Sustained Virologic Response (SVR24)

  Week 24 of follow-up period

• The proportion of patients achieved End of Treatment Response (ETR)

  Week 12 of treatment

• The proportion of patients achieved Sustained Virologic Response (SVR4)

  Week 4 of follow-up period

• The proportion of patients developed Viral Breakthrough

  Week 12 of treatment

• The proportion of patients Relapsed

  Week 12 of follow-up period

Other Outcomes (6)

• Number of patients with Adverse Events

  From initiation of treatment up to week 24 of follow-up period

• Number of patients with Serious Adverse Events

  From initiation of treatment up to week 24 of follow-up period

• Number of patients with Adverse Event leading to permanent discontinuation of the studying treatment regimen

  From initiation of treatment up to week 24 of follow-up period

Study Arms (1)

Narlaprevir + Ritonavir + Daclatasvir

EXPERIMENTAL

All of enrolled patients receive equal study therapy with Narlaprevir/Ritonavir/Daclatasvir daily for 12 weeks

Drug: Narlaprevir; Drug: Ritonavir; Drug: Daclatasvir

Interventions

Narlaprevir DRUG

100 mg, oval shaped, concave, yellow film-coated, tablets taken as 200 mg per os daily

Also known as: Arlansa

Narlaprevir + Ritonavir + Daclatasvir

Ritonavir DRUG

100 mg, tablets, taken as 100 mg per os daily

Also known as: Norvir

Narlaprevir + Ritonavir + Daclatasvir

Daclatasvir DRUG

60 mg, tablets, taken as 60 mg per os daily

Also known as: Daklinza

Narlaprevir + Ritonavir + Daclatasvir

Eligibility Criteria

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

You may qualify if:

• Subjects who meet all of the following criteria are eligible for participation in the study:
• 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 1b at screening as determined by the Central Laboratory. Any non definitive results must exclude the subject from study participation.
• Minimum HCV-RNA level of ≥10,000 IU 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 kPa within 6 months of baseline/Day1;
• FibroTest score of ≤ 0.48 AND 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);

You may not qualify if:

• Subjects with any of the following are not eligible for participation in the study:
• Had prior exposure to IFN, RBV, or other approved or experimental 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.
• Сhronic 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 (list of drugs with expected drug-drug interactions due to concomitant ritonavir usage)

Sponsors & Collaborators

• R-Pharm: lead
• Almedis: collaborator

Study Sites (4)

FBIS CSRI of Epidemiology of Federal Service on Customers

Moscow, Russia

Location

SBEI HPE Moscow State Medical and Dental University n.a. A.I. Evdokimov of Ministry of Health of Russia

Moscow, Russia

Location

SBHI of Moscow "City Clinical Hospital #24"

Moscow, Russia

Location

St. Petersburg SBHI Center of Prevention and Fight against AIDS and Infection Diseases

Saint Petersburg, Russia

Location

MeSH Terms

Conditions

Hepatitis C; Bronchiolitis Obliterans Syndrome

Interventions

narlaprevir; Ritonavir; daclatasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: April 2, 2018
• Study Start: November 27, 2017
• Primary Completion: August 29, 2018
• Study Completion: November 21, 2018
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

RU (4)