Status:
COMPLETED
Efficacy and Safety of All-Oral Combination of Narlaprevir/Ritonavir and Daclatasvir in Treatment-Naїve Patients With Chronic Hepatitis C Genotype 1b
Lead Sponsor:
R-Pharm
Collaborating Sponsors:
Almedis
Conditions:
Chronic Hepatitis C Genotype 1b
Eligibility:
All Genders
18-70 years
Phase:
PHASE2
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) genot...
Detailed Description
To evaluate effectiveness and safety of treatment with Narlaprevir, Ritonavir and Daclatasvir combination will be selected 105 treatment-naїve patients with chronic HCV genotype 1b without genetic var...
Eligibility Criteria
Inclusion
- Inclusion Criteria -
- 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);
- aspartate aminotransferase (AST) ≤ 10 x ULN;
- Hemoglobin ≥ 12g/dL for male, ≥ 11g/dL for female subjects;
- Platelets ≥ 50,000cells/mm3;
- International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR;
- Albumin ≥ 3g/dL;
- Direct bilirubin ≤ 1.5 x ULN;
- Hemoglobin A1c (HbA1c) ≤ 10%;
- Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation;
- Have not been treated with any investigational drug or device within 30 days of the screening visit.
- A female subject is eligible to enter the study if it is confirmed that she is:
- Not pregnant or nursing;
- Of non-childbearing potential (i.e., women who have had a hysterectomy, both ovaries removed, or medically documented ovarian failure, or are postmenopausal women \>50 years of age with cessation \[for ≥12 months\] of previously occurring menses), or
- Of childbearing potential (i.e., women who had not had a hysterectomy, both ovaries removed, or medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea are considered to be of childbearing potential. These women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the baseline/Day 1 visit prior to enrollment. They must also agree to one of the following from 3 weeks prior to baseline/Day 1 until 6 months after last dose of the investigational drugs:
- Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, sympto thermal, post-ovulation methods) is not permitted Or
- Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from the date of screening until 6 months after the last dose of the investigational drugs:
- intrauterine device (IUD) with a failure rate of \< 1% per year;
- female barrier method: cervical cap or diaphragm with spermicidal agent;
- tubal sterilization;
- vasectomy in male partner; Women of childbearing potential must not rely on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to screening must stop their contraceptive regimen use from the date of screening until 6 months after their last dose of investigational drugs.
- All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of screening until 6 months after their last dose of investigational drugs:
- implants of levonorgestrel;
- injectable progesterone;
- oral contraceptives (either combined or progesterone only);
- contraceptive vaginal ring;
- transdermal contraceptive patch;
- Male subjects must agree to refrain from sperm donation for at least 6 months after the last dose of investigational drugs.
- Are in generally good health as determined by the investigator.
- Are able to comply with the dosing instructions for study drug administration and are able to complete the study schedule of assessments.
- Exclusion Criteria -
- 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)
- Have known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients.
- Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93 С/H/N/S and/or L31 F/M/V/I amino acid substitutions at Screening.
Exclusion
Key Trial Info
Start Date :
November 27 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 21 2018
Estimated Enrollment :
105 Patients enrolled
Trial Details
Trial ID
NCT03485846
Start Date
November 27 2017
End Date
November 21 2018
Last Update
December 19 2018
Active Locations (4)
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1
FBIS CSRI of Epidemiology of Federal Service on Customers
Moscow, Russia
2
SBEI HPE Moscow State Medical and Dental University n.a. A.I. Evdokimov of Ministry of Health of Russia
Moscow, Russia
3
SBHI of Moscow "City Clinical Hospital #24"
Moscow, Russia
4
St. Petersburg SBHI Center of Prevention and Fight against AIDS and Infection Diseases
Saint Petersburg, Russia