Inflammation of the liver caused by a virus
Conditions
Interventions
Participants will receive six or twelve 12 weeks of open-label
sofosbuvir/velpatasvir (400mg/100mg daily) in an oral once-daily fixed dose
combination. Dose modifications are prohibited.
Sponsors
The Kirby Institute, The University of New South Wales Australia
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible to participate in this study. ;1 Participants have voluntarily signed the informed consent form. 2 18 years of age or older. 3 Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the investigator is unlikely to demonstrate spontaneous viral clearance 4 HCV genotypes 1-6. 5 HBsAg negative 6 Negative pregnancy test at baseline (females of childbearing potential only). 7 Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception 8 Medically stable on the basis of physical examination, medical history and vital signs 9 Adequate literacy to provide reliable responses to the study questionnaires 10 All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end. 11 Recently acquired HCV infection (estimated duration of infection 10 X ULN) within the previous 6 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable;OR;C) For cases of recent HCV reinfection the following criteria are required: Documented prior HCV antibody positive with HCV RNA negative on at least 2 occasions 6 months apart AND new HCV RNA positive within the previous 6 months ;*Estimated duration of infection based on midpoint between last antibody negative or HCV RNA and first antibody positive or HCV RNA in the case of seroconversion and 6 weeks prior to date of maximum ALT in the case of acute hepatitis.;If co-infection with HIV is documented, the subject must meet the following criteria: 1. Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with CD4 T cell count >500 cells/mm3 OR 2. On a stable ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and an undetectable plasma HIV RNA level. • Suitable ARV include: o Nucleos(t)ide reverse transcriptase inhibitors: Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), emtricitabine (FTC)Non-nucleoside reverse transcriptase inhibitors: Rilpivirine o Protease inhibitors: Atazanavir, darunavir, lopinavir, ritonavir o Integrase inhibitors: Dolutegravir, raltegravir, elvitegravir/cobicistat • Contraindicated ARV include: o Efavirenz * - 50% reduction in velpatasvir (GS-5816) exposure o Didanosine o Zidovudine o Tipranavir Other ARV agents may be permissible at the time of study commencement pending further drug-drug interaction studies; please discuss with the Medical Monitor.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the exclusion criteria are not to be enrolled in this study.;1 History of any of the following: a. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded. b. History of chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study c. Solid organ transplant d. Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded. e. Significant drug allergy (such as anaphylaxis or hepatotoxicity) 2. Subject has a known or documented prior history of cirrhosis 3 Subject shows evidence of significant liver disease in addition to hepatitis C, which may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson*s disease, non-alcoholic steatohepatitis (NASH), or primary biliary cirrhosis 4 Any of the following lab parameters at screening: a. Direct bilirubin > 1.5 x ULN b. Platelets 1.5 (unless subject is on a stable anticoagulant regimen or has known coagulopathy) 5 Pregnant or nursing female 6 Use of prohibited concomitant medications as described in the study protocol 7 Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day) 8 Known hypersensitivity to velpatasvir, sofosbuvir or formulation excipients. 9 Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the proportion of participants with HCV RNA below the level of quantitation (target not detected [TND] or target detected, not quantifiable [TDnq]) at 12 weeks post end of treatment (SVR12) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary virological endpoints: 1) The proportion of participants with: - ETR defined as HCV RNA below the level of quantitation at end of therapy - SVR 4 defined as HCV RNA below the level of quantitation 4 weeks post therapy - SVR 24 defined as HCV RNA below the level of quantitation 24 weeks post therapy - HCV RNA below the level of quantitation through 2 years post treatment Results will be stratified by HCV genotype and HIV-coinfection. 2) 80/80 adherence: Defined as the receipt of >80% of scheduled doses for >80% of the scheduled treatment period. 3) 90/90 adherence: Defined as the receipt of >90% of scheduled doses for >90% of the scheduled treatment period. 4) 100/100 adherence: Defined as the receipt of 100% of scheduled doses for 100% of the scheduled treatment period. 5) On-treatment adherence: Calculated by subtracting the number of missed doses from the total number of doses of scheduled treatment and dividing by the total intended therapy duration. This measures the proportion of doses received from the time that treatment was initiated until treatment was discontinued or completed. 6) Toxicity: Proportion of participants with at least one severe or potentially life threatening (grade 3 or 4) adverse event. 7) Early treatment discontinuation: Discontinuation of therapy prior to the per-protocol planned end of treatment (6 or 12 weeks depending on study arm). 8) Resistance associated variants (RAVs): The proportion of treated subjects with development of RAVs following virological relapse or breakthrough. 9) Reinfection rate: Rates of HCV reinfection will be calculated using person-time of observation during and up to 48 months following end of treatment. 10) Baseline characteristics, on-treatment adherence, risk behaviours and toxicity will be evaluated among subjects withdrawing prior to randomisation. | — |
Countries
Netherlands
Outcome results
None listed