Adults with acute genotype 1 hepatitis C virus (HCV) infection MedDRA version: 18.1 Level: LLT Classification code 10072848 Term: Hepatitis C virus genotype 1 positive System Organ Class: 100000004848 MedDRA version: 18.1 Level: PT Classification code 10065051 Term: Acute hepatitis C System Organ Class: 10021881 - Infections and infestations MedDRA version: 18.1 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 100000004848
Conditions
Interventions
Product Name: Ledipasvir/sofosbuvir fixed-dose combination
Product Code: LDV/SOF FDC
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOF
CAS Number: 1190307-88-0
Current Sponsor code: G
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. 1. Willing and able to provide written informed consent 2. Male or female, age =18 years 3. HCV RNA = 103 IU/mL at Screening 4. Confirmation of acute genotype 1 HCV infection documented by either: documented seroconversion to HCV antibody positivity within the 4 months preceding screening or known or suspected exposure to HCV within the 4 months preceding screening with 10 times elevated serum ALT level at screening or 4 weeks preceding screening without evidence of confounding liver disorders 5. If the patient visits a physician due to symptoms of acute HCV, no greater than a 12 week interval may have elapsed between the time of the visit and screening 6. Non-cirrhotic. Absence of cirrhosis will be determined based on clinical parameter or ultrasound. 7. Body mass index (BMI) = 18 kg/m2 8. Screening ECG without clinically significant abnormalities 9. Subjects must have the following laboratory parameters at screening: a) Hemoglobin = 10 g/dL b) Platelets = 90,000/µL c) INR =1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR d) Albumin =3 g/dL e) HbA1c =10% f) Creatinine clearance (CLcr) =60 mL/min, as calculated by the Cockcroft-Gault equation (Cockcroft and Gault 1976) 10. Subject has not been treated with any investigational drug or device within 42 days of the Screening visit 11. A negative serum pregnancy test is required for female subjects (unless surgically sterile or women = 54 years of age with cessation for 24 = months of previously occurring menses, see Appendix 2 for definitions). Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted. or Consistent and correct use of 1 of the following methods of birth control listed below, in addition to a male partner who correctly uses a condom, from the date of Screening until 30 days after last dose of study drug: • intrauterine device (IUD) with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. 1. Clinically-significant illness (other than HCV) or any other major medical disorder that, in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. 2. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug (for example, gastric bypass or severe ulcerative colitis). 3. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. 4. Clinical hepatic decompensation (i.e., clinical ascites, encephalopathy or variceal hemorrhage). 5. Solid organ transplantation. 6. Significant pulmonary disease or significant cardiac disease. 7. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 2 years. Subjects with psychiatric illness that is well-controlled on a stable treatment regimen for at least 12 months prior to screening or has not required medication in the last 12 months may be included. 8. Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. 9. Significant drug allergy (such as anaphylaxis or hepatotoxicity). 10. Any prior treatment for HCV infection including prior exposure to any inhibitor of the NS5B and NS5A. 11. Pregnant or nursing female or male with pregnant female partner. 12. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, Wilson’s disease, a1 antitrypsin deficiency, cholangitis). 13. Infection with hepatitis B virus (HBV; defined as HBsAg-positive) or human immunodeficiency virus (HIV). 14. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day) 15. Clinically-relevant drug or alcohol abuse within 12 months of screening including any uncontrolled drug use within 6 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator. Uncontrolled users of intravenous drugs will not be permitted to enroll in the study. 16. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1. 17. Use of any prohibited concomitant medications as described in Section 5.4 within 21 days of the Baseline/Day 1 visit. Use of Amiodaron as concomitant medication is prohibited as described in Section 5.4 within 60 days of Baseline/Day 1 visit. 18. Known hypersensitivity to LDV, SOF or formulation excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are as follows: • To evaluate the efficacy of treatment with ledipasvir (LDV)/sofosbuvir (SOF) FDC for 6 weeks in patients with acute genotype 1 HCV infection as measured by the proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) 12 weeks after discontinuation of therapy (SVR12) • To evaluate the safety and tolerability of LDV/SOF FDC -containing regimens administered for up to 6 weeks in patients with acute genotype 1 HCV infection ;Secondary Objective: The secondary objectives of this study are as follows: • To determine the durability of response 24 weeks after discontinuation of therapy (SVR24) measured by the proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) 24 weeks after discontinuation of therapy (SVR 24) • To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation measured as mean viral load during treatment (Baseline, week 2, 4, 6) and after treatment discontinuation (Follow up week 4, 12, 24) • To evaluate the emergence of viral resistance to LDV/SOF FDC during treatment and after treatment discontinuation The exploratory objectives of this study are as follows: • To assess any relationship between HCV-specific T cell responses and treatment efficacy • To assess any relationship between NK cell phenotype and function and treatment efficacy • To assess any relationship between circulating serum chemokines and treatment efficacy and safety;Primary end point(s): • To evaluate the efficacy of treatment with ledipasvir (LDV)/sofosbuvir (SOF) FDC for 6 weeks in patients with acute genotype 1 HCV infection as measured by the proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) 12 weeks after discontinuation of therapy (SVR12) • To evaluate the safety and tolerability of LDV/SOF FDC-containing regimens administered for up to 6 weeks in patients with acute genotype 1 HCV infection;Timepoint(s) of evaluati | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) 24 weeks after discontinuation 2) measurements every Visit 3) measurements every Visit 4) measurements every Visit 5) measurements every Visit 6) measurements every Visit;Secondary end point(s): • To determine the durability of response 24 weeks after discontinuation of therapy (SVR24) • To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation • To evaluate the emergence of viral resistance to LDV/SOF FDC during treatment and after treatment discontinuation The exploratory objectives of this study are as follows: • To assess any relationship between HCV-specific T cell responses and treatment efficacy • To assess any relationship between NK cell phenotype and function and treatment efficacy • To assess any relationship between circulating serum chemokines and treatment efficacy | — |
Countries
Germany
Contacts
Public ContactProf. Dr. med. Michael Manns
Hannover Medical School
Outcome results
None listed