Patients with chronic hepatitis C MedDRA version: 19.1 Level: LLT Classification code 10074391 Term: Chronic hepatitis C virus genotype 1 System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Harvoni
Pharmaceutical Form:
INN or Proposed INN: sofosbuvir
CAS Number: 1190307-88-0
Other descriptive name: SOFOSBUVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients of both sexes between 18-70 years • Patients are followed at one of the 18 departments affiliated with DANHEP, diagnosed with chronic HCV infection (verified by real-time PCR as the presence of HCV RNA in two blood samples taken 6 months apart). • Treatment-naïve or previous treatment with pegylated interferon / ribavirin or discontinuing treatment with pegylated interferon / ribavirin / telaprevir / boceprevir due to side effects. • Treatment demanding chronic hepatitis C virus infection. • Liver biopsy or Fibroscanning showing moderate to severe fibrosis (Metavir =F2 score) or cirrhosis. Liver fibrosis or cirrhosis examined by liver biopsy ranked by the Danish scoring system based on the Metavir scoring system, where stage F2 indicate moderate fibrosis stage F3; severe fibrosis and stage F4; cirrhosis. If the diagnosis is made with Fibroscanning; values> 7 kPa and 1.7 (increased clotting of the blood) , serum albumin =65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: Hypersensitivity to any of the ingredients in the medicine. • Severe untreated psychiatric illness which the investigator believe may affect treatment. • Severe mental illness; schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder, mania. • Current alcohol (> 25 objects weekly), intravenous drug or other drug abuse. • Decompensated cirrhosis. • Diagnosed with hepatocellular carcinoma or are being investigated for this. • Severe heart failure NYHA class III and IV • Previous stroke, TIA or AMI. • Severe angina pectoris, cardiomyopathy, pulmonary hypertension, uncontrolled hypertension or significant arrhythmia diagnosed by ECG. • Severe chronic lung disease; COPD, pulmonary fibrosis or sarcoidosis defined as; GOLD stage 3: FEV1 / FVC 8.5%. • Severe hepatic impairment (Child-Pugh C). • The use of contraceptives with ethinylestradiol • Treatment with CYP3A4 substrates; Alfuzosin, amiodarone, Atorvastatin, ergotamine, Fusidic acid, Lovastatin, Oral midazolam, pimozide, Quetiapine, Salmeterol, Sildenafil against pulmonary arterial hypertension, Simvastatin, Triazolam, Rosuvastatin. • Treatment with potent CYP3A4 inducers or other enzyme inducers; Efavirenz, etravirine, Enzalutamid, Mitotane, Nevirapine, Phenobarbital. • The treatment with strong CYP3A4 inhibitors; Clarithromycin, Cobicistat, itraconazole, lopinavir / ritonavir, posaconazole, voriconazole. • Treatment with strong CYP2C8 inhibitors; Gemfibrozil.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the rate of adverse events and sustanied viral response in a randomized study of patients with chronic hepatitis C, genotype 1 patients, treated for 12 weeks with Viekira PAK® and ribavirin versus Harvoni® and ribavirin. Compare the adverse events- and sustanied viral response rates between the two groups of patients in each treatment arm in relation to demographic, biological and genetic factors. ;Secondary Objective: To investigate, by population sequencing for resistance associated varients, hepatitis C virus isolated from all patients who fail treatment in the randomised study described above both at baseline and post-treatment failure. Examine the effect of sofosbuvir/daclatasvir/ribavirin or sofosbuvir/velpatasvir with and without ribavirin for 12 weeks on the hepatic venous pressure gradient, systemic blood pressure, metabolic function of the liver and inflammatory cells in patients with chronic hepatitis C, genotype 3 and liver cirrhosis. To study if there is a change in perfusion of the heart and calcium score analyzed by heart - rubidium PET/CT scan, after treatment with direct acting antivirals for 8, 12 or 24 weeks in patients with chronic hepatitis C, genotype 1 or 3. ;Primary end point(s): The frequency of side effects seen when treated for 12 weeks with Viekira PAK + Exviera® and ribavirin versus Harvoni® and ribavirin in patients with chronic hepatitis C infected with genotype 1.;Timepoint(s) of evaluation of this end point: After end of treatment of the last included patient in the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Treatment response defined as following: - Sustained virological response (SVR): negative HCV RNA 12 weeks after end of treatment. - Virus breakthrough: HCV RNA decreases during treatment (undetectable levels can be seen), followed by a clinically relevant increase of HCV RNA during treatment. - Partial response:> 2 log drop in HCV RNA, but the viral load remains above the lowest measurable level after 12 weeks of treatment. - Relapse: negative HCV RNA during treatment but relapse of HCV RNA after treatment is completed. - Non-response: no effect of treatment. The patient is persistent HCV RNA positive, despite treatment. - Date of birth, sex and ethnicity - Country of origin. - Previous treatment and treatment response. - Hepatitis B and / or HIV infection. - Mode of transmission. - IL-28B genotype and subtype. - Liver fibrosis / cirrhosis status at baseline and liver transplantations status. - Start and end dates of treatment, hepatitis C viral load (HCV RNA titers) and alanine transaminase (ALT) levels at baseline and during treatment at weeks 1, 2, 4, 8, 12 and at week 4, 8, 12 after end of treatment. - Viral resistance evaluated by population sequencing of the hepatitis C virus genome in patients with treatment failure in Study I. - The immune systems response to DAA treatment evaluated by measuring the number of T cells and the amount of antibodies produced by B cells before, during and after treatment for participants enrolled at Copenhagen University Hospital, Hvidovre. - A reduction in the degree of inflammation in the liver and macrophage activation determined by the level of sCD163. - Change in hepatic venous pressure determined by HVPG - Changes in the metabolic liver function determined by GEC. - Change in the degree of liver fibrosis measured by Fibroscan. - Changes in MELD and Child-Pugh score - Changes in the level of liver enzymes, albumin, INR, platelets and alpha-fetoprotein. - Changes in the levels | — |
Countries
Denmark
Contacts
Public ContactNina Weis
Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.
Outcome results
None listed