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.
Two patient cohorts were anticipated in this study: 1. Cohort A: 60 treatment-naive patients were 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) were enrolled into narlaprevir/ritonavir/sofosbuvir treatment for 8 weeks. The enrollment of 25 treatment-naïve patients with low viral load into 8 week cohort started after completion of enrollment of 60 treatment-naive patients into 12 week cohort. The study included 3 time periods: 1. Screening period with duration up to 2 weeks during which study eligibility was confirmed. 2. Active treatment period (for 12 or 8 weeks): patients in the Cohort A were receiving study therapy with narlaprevir/ritonavir/sofosbuvir for 12 weeks, in the Cohort B - during 8 weeks. If a patient had virologic breakthrough while receiving therapy, discontinuation of antiviral treatment was advised with appropriate clinical follow-up. 3. Follow-up period during which patients did not receive any study medication. The duration of the follow-up period after the end of study treatment was 24 weeks. Overall, each patient had been participating in the study for approximately up to 38 weeks from the time the patient signed the Informed Consent Form through the final visit. If a patient had a screening failure, but was rescreened and subsequently enrolled, the reason for the original screening failure must have been documented in the source documents. A new subject Identification number (ID) was assigned to the patient. The recruitment period in this study was planned to be up to 6 months. The total period of the study was anticipated to be approximately 1 year 3 months. The patient was considered to be completed the study upon the completion of the last protocol specified visit. For those patients who did not complete the study, patient participation was considered terminated upon the completion of the last visit or contact (e.g., phone contact with the investigator). It was estimated that 85 patients meeting inclusion/exclusion criteria would be recruited from approximately 6 clinical sites in Russia.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
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.
100 mg tablets taken as 100 mg per os once daily. 30 tablets in bottle
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.
FBIS CSRI of Epidemiology of Federal Service on Customers
Moscow, Russia
FSIS FRC of food and biotechnology
Moscow, Russia
SBEI HPE MSMDU n.a. A.I. Evdokimov of Ministry of Health of Russia
Moscow, Russia
FSBI HEI HPE Military Medical Academy n.a. S.M. Kirov
Saint Petersburg, Russia
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
Time frame: Week 12 of follow-up period (SVR12) - week 24 of the study
The proportion of patients who achieved the Sustained Virological Response 24 weeks after the end of treatment (SVR24) in 12-week cohort
HCV RNA undetectable by LOD; for 12-week cohort patients
Time frame: 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
HCV RNA \<LOD at the treatment end;
Time frame: 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
HCV RNA \<LOD 4 weeks after the end of treatment
Time frame: 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
applicable for cohort A patients only; viral breakthrough defined as greater than or equal to 1 log10 increase in HCV-RNA above nadir, or detectable HCV-RNA, while on treatment after an initial drop below detection in 12-week cohort. Viral breakthrough is an unsatisfactory therapeutic effect. in this case discontinuation of antiviral treatment is advised with appropriate clinical follow-up. Viral breakthrough will be summarized by patient cohort and treatment regimen. The number and proportion of patients achieving undetectable HCV RNA at each time point will be summarized. Time to breakthrough will be estimated using the Kaplan - Meier method if applicable
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SPb SBIH Center on preventiomn and treatment of AIDS and infectional deseases
Saint Petersburg, Russia
Time frame: week 12 of the study
The proportion of patients received 12 weeks of study treatment who developed relapse
applicable for cohort A patients only; relapse presence is defined as HCV RNA undetectable by LOD at the end of treatment with subsequent detectable HCV RNA at the end of the follow-up period (week 12) in 12-week cohort;
Time frame: week 12 of the study and week 24 of the study