Adult patients chronically infected with genotype 3 hepatitis C virus with cirrhosis MedDRA version: 20.0 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Epclusa
Product Name: Epclusa
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sofosbuvir
Concentration unit: mg
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Voluntarily signed informed consent form • Aged 18 years or older • Chronic HCV infection, defined by anti-HCV antibody or HCV RNA detection for greater than 6 months • Infected with genotype 3 HCV (identified by referring hospital) • Meets NHS England treatment criteria to commence sofosbuvir/velpatasvir • Pre-treatment HCV RNA >10,000 iu/mL (can be any time before treatment week 0) • HCV RNA > or equal to 30 iu/mL at treatment week 2 (+/- 3 days) • Has cirrhosis defined by: evidence of portal hypertension, OR APRI >2 plus AST:ALT ratio >1, OR radiological evidence of cirrhosis, OR fibroscan score >11.5kPa, OR liver biopsy showing cirrhosis • Patients with decompensated cirrhosis (variceal bleeding, ascites and encephalopathy) can be included • Patients with malignancy including hepatocellular carcinoma can be included • Patients with liver transplant can be included • Patients coinfected with chronic hepatitis B virus or human immunodeficiency virus can be included • Female subjects of childbearing potential must have documented negative pregnancy test prior to enrolment (negative urinary pregnancy test), and if engaged in heterosexual intercourse must use protocol specified method of contraception (see below) during study drug treatment and for 30 days after last dose • Male subjects engaged in heterosexual intercourse with a female of childbearing potential should protocol specified method of contraception during study drug treatment and for 30 days after last dose Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Any of the above inclusion criteria not met • Any of the following criteria excludes a subject from enrolling into this study • Clinically-significant medical or psychiatric illness (other than chronic HCV) in the past, present, or being evaluated, that may interfere with participant treatment, safety, assessment or compliance with the protocol. • Severe renal impairment with eGFR <30 mL/min/1.73m2 or requiring dialysis • Alcohol consumption or illicit drug abuse likely to interfere with participant treatment, safety, assessment or compliance with protocol, as deemed by the investigator • Previous exposure to sofosbuvir (or other NS5B inhibitor) or NS5A inhibitor • Severe allergy to study drugs, its metabolites or formulation excipient (see SmPC for details) • Any investigational medicinal product = 6 weeks prior to treatment start • Pregnant or nursing female, or males wishing to conceive during the period of study treatment + 30 days after • Patients who adhered to less than 90% of prescribed sofosbuvir/velpatasvir at screening • In accordance with the SmPC of sofosbuvir/velpatasvir concomitant use of the following medications are contraindicated: Anticonvulsants - carbamazepine, phenytoin, phenobarbital, oxcarbazepine Antimycobacterials – rifampicin, rifabutin, rifapentine Antiretrovirals - efavirenz St John’s wort Modafinil Proton-pump inhibitors should be avoided and if necessary, should be administered 4 hours after at maximum doses equivalent to 20mg omeprazole per day. Amiodarone should be avoided and if necessary, close monitoring is required Please consult the SmPC and Section 15.16 and 17 for list of medications to be used with caution or monitoring. Participants taking these medications must have discontinued prior to starting sofosbuvir/velpatasvir (this is expected to be in line with standard care practice). Definition of child-bearing potential and effective contraception: Subjects are considered not of child-bearing potential if they are surgically sterile (undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (women aged = 45 years of age with cessation of previously occurring menses for = 12 months) or they have medically-documented ovarian failure. Effective contraception include: • True abstinence: when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence, e.g. calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) • Male partner vasectomy or other medical condition causing azoospermia • Male partner using condom • Intrauterine device • Female barrier method (cervical cap or diaphragm with spermicidal agent) • Tubal sterilisation • Levonorgestrel implant • Injectable progesterone • Oral contraceptive (combined or progesterone only) • Contraceptive vaginal ring • Transdermal contracep
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This trial will study the treatment effectiveness of sofosbuvir/velpatasvir for 12 or 24 weeks, in patients infected with genotype 3 hepatitis C virus, with advanced liver disease (cirrhosis), who are slow responders to treatment with persistent virus after the first two weeks of treatment. This trial will answer if identifying patients by their viral response during treatment (whether the virus is cleared after the first two weeks) can guide the duration of therapy required to achieve cure. ; Secondary Objective: This study will compare the tolerability and side effects experienced by patients treated with 12 or 24 weeks of sofosbuvir/velpatasvir. Specifically it will study the frequency of serious adverse events and requirements for stopping treatment prematurely. The study will evaluate quality of life following treatment, using a standardised questionnaire. ; Primary end point(s): To compare the efficacy (the proportion of randomised patients who achieve a sustained virological response – defined as undetectable HCV RNA (below limit of quantification up to 15 iu/mL) at 12 weeks (up to 16 weeks) after end of treatment – SVR12) of 12 OR 24 weeks of sofosbuvir/velpatasvir in patients with genotype 3 chronic HCV and cirrhosis, who have detectable viraemia (= 30 iu/mL) at week 2 (+/- 3 days) of treatment with sofosbuvir/velpatasvir. Patients randomised must have completed at least 90% of sofosbuvir/velpatasvir at screening, and patients randomised to 24 weeks must have taken at least one dose of the extension phase treatment. ;Timepoint(s) of evaluation of this end point: 12 weeks post completion of treatment (whether 12 or 24 weeks in total) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the safety and tolerability of sofosbuvir/velpatasvir for 12 and 24 weeks. To assess patient reported outcomes (defined as SF36 scores at the end of therapy) in patients receiving 12 or 24 weeks of sofosbuvir/velpatasvir ;Timepoint(s) of evaluation of this end point: 12 weeks post completion of treatment (whether 12 or 24 weeks in total) | — |
Countries
United Kingdom
Contacts
Public ContactDr Sally Burtles
Queen Mary University of London
Outcome results
None listed