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

  • STATUS
    Recruiting
  • End date
    Jan 1, 2022
  • participants needed
    85
  • sponsor
    R-Pharm
Updated on 23 January 2021

Summary

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

Description

Two patient cohorts are anticipated in this study:

  1. Cohort A: 60 treatment-naive patients will be enrolled into narlaprevir/ritonavir/sofosbuvir treatment for 12 weeks.
  2. Cohort B: (exploratory): 25 treatment-naive patients with low viral load (HCV RNA<1000000 IU/L) will be enrolled into narlaprevir/ritonavir/sofosbuvir treatment for 8 weeks.

The enrollment of 25 treatment-nave patients with low viral load into 8 week cohort will start after completion of enrollment of 60 treatment-naive patients into 12 week cohort.

The study will include 3 time periods:

  1. Screening period with duration up to 2 weeks during which study eligibility will be confirmed.
  2. Active treatment period (for 12 or 8 weeks): patients in the Cohort A will receive study therapy with narlaprevir/ritonavir/sofosbuvir for 12 weeks, in the Cohort B - during 8 weeks.

If a patient has virologic breakthrough while receiving therapy, discontinuation of antiviral treatment is advised with appropriate clinical follow-up.

3. Follow-up period during which patients do not receive any study medication. The duration of the follow-up period after the end of study treatment will be 24 weeks.

Overall, each patient will participate in the study for approximately up to 38 weeks from the time the patient signs the Informed Consent Form through the final visit.

If a patient is a screening failure, but is rescreened and subsequently enrolled, the reason for the original screening failure must be documented in the source documents. A new subject Identification number (ID) will be assigned to the patient.

The recruitment period in this study is planned to be up to 6 months. The total period of the study is anticipated to be approximately 1 year 3 months.

The patient is considered to be completed the study upon the completion of the last protocol specified visit. For those patients who do not complete the study, patient participation will be considered terminated upon the completion of the last visit or contact (e.g., phone contact with the investigator).

It is estimated that 85 patients meeting inclusion/exclusion criteria will be recruited from approximately 6 clinical sites in Russia

Details
Condition Chronic Hepatitis c Genotype 1
Treatment Ritonavir, Sofosbuvir, Narlaprevir
Clinical Study IdentifierNCT04246723
SponsorR-Pharm
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

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
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
Hemoglobin 12g/dL for male, 11g/dL for female subjects
Platelets 50,000cells/mm^3 (for patients in 8-week study treatment group - 150,000 cells/mm3)
International normalized ratio (INR) 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
Albumin 3 g/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 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
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, 1-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
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