Direct acting antiviral therapy of hepatitis C in Denmark: treatment response, adverse events and resistance associated variants

Phase 1

• Conditions: Patients with chronic hepatitis C; MedDRA version: 19.1Level: LLTClassification code 10074391Term: Chronic hepatitis C virus genotype 1System Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2015-001956-31-DK
• Lead Sponsor: Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-10
• Last Update Posted: 4 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 111

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 <17kPa indicate moderate to severe fibrosis and values =17 kPa indicate cirrhosis.
- Clinically diagnosed cirrhosis in the absence of liver biopsy or Fibroscanning, defined as overt cirrhosis at ultrasound (+/- spleen enlargement), low platelet count =110 * 109 cells / L, PT=75 / INR> 1.7 (increased clotting of the blood) , serum albumin <6g / L or the presence of complications: ascites confirmed by ultrasound, esophageal varices diagnosed by gastroscopy or hepatic encephalopathy.
• Infected with genotype 1 or genotype 3.
• Women of childbearing potential must use effective contraception defined as copper or progesten spiral and condom must be used by partner throughout the treatment period.
• Men who are treated in the trial must use condoms throughout treatment and for at least 7 months after completion of treatment.
• Must be able to read and understand Danish.
• Must be able to sign informed consent.
• patients co-infected with HIV must be in anti-viral therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

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 <0.7 and FEV1 between 30-50% predicted and GOLD stage 4: FEV1 / FVC <0.7 and FEV1 between the 30% predicted.
• Myelodysplastic diseases.
• Organ transplantation (except from hair or cornea)
• Active cancer or diagnosed with cancer (other than basal cell skin cancer) within the past 5 years.
• Autoimmune liver disease.
• Haemoglobinopathies; sickle cell anemia and thalassemia.
• Neutropenia <1.5 x 103 l
• Thrombocytopenia <50 x 103 ul
• Renal impairment (GFR <50 ml / min., Including hemodialysis)
• thyroid disease that is not controlled by conventional therapy.
• Insufficient treated epilepsy.
• Pregnancy / lactation.
• Severe untreated anemia, hemoglobin = 5 mmol / l.
• Treatment with carbamazepine, phenytoin, rifabutin, rifampicin, herbal preparations containing St. John's wort and modafinil.
• Insufficient treated severe diabetes, HbA1c> 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified