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

• Status: Recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm
• Collaborators: Almedis; ChromSystemsLab; Scientific Center EFiS
• Treatments: Ritonavir; Sofosbuvir

Criteria

Inclusion Criteria:

• 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:

1. Liver biopsy within 2 years of screening showing absence of cirrhosis

2. Fibroscan® with a result of ≤ 12.5 kilopascal (kPa) within 6 months of baseline/Day1

3. 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:

1. alanine aminotransferase (ALT) ≤ 10 x the upper limit of normal (ULN)

2. AST ≤ 10 x ULN

3. Hemoglobin ≥ 12g/dL for male, ≥ 11g/dL for female subjects

4. Platelets ≥ 50,000cells/mm^3 (for patients in 8-week study treatment group - ≥ 150,000 cells/mm3)

5. International normalized ratio (INR) ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR

6. Albumin ≥ 3 g/dL;

7. Direct bilirubin ≤ 1.5 x ULN;

8. Hemoglobin A1c (HbA1c) ≤10%;

e. 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:

1. Not pregnant or nursing;

2. Of nonchildbearing 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

3. 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 the screening until 6 months after last dose of the investigational drugs:

• Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.

• 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. 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.

• intrauterine device (IUD) with a failure rate of < 1 %;

• female barrier method: cervical cap or diaphragm with spermicidal agent

• tubal sterilization

• vasectomy in male partner

• All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the nonhormonal 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:

• 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.