Acute Hepatitis C
Conditions
Keywords
acute HCV Genotype 1 Infection, HCV RNA, LDV/SOF FDC
Brief summary
This is an open-label, single arm, multicenter, pilot-study to compare the efficacy and safety of LDV/SOF fixed dose combination (FDC) in subjects with acute genotype 1 HCV infection. A total of 20 subjects will be assigned to receive LDV/SOF FDC tablet (LDV 90 mg/SOF 400 mg/) once daily for 6 weeks.Patients will be followed up for 24 weeks.
Interventions
DRUGLDV/SOF FDC
Ledipasvir/Sofosbuvir fixed dose combination (FDC) tablet (LDV 90 mg/SOF 400 mg) once daily
Sponsors
Hannover Medical School
Gilead Sciences
HepNet Study House, German Liverfoundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 parameters 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: 1. Hemoglobin ≥ 10 g/dL 2. Platelets ≥ 90,000/µL 3. INR ≤1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR 4. Albumin ≥ 3 g/dL 5. HbA1c ≤ 10% 6. Creatinine clearance (CLcr) ≥ 60 mL/min, as calculated by the Cockcroft- Gault equation 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). 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 \< 1% per year * female barrier method: cervical cap or diaphragm with spermicidal agent * tubal sterilization * vasectomy in male partner * hormone-containing contraceptive: * implants of levonorgestrel * injectable progesterone * oral contraceptives (either combined or progesterone only) * contraceptive vaginal ring * transdermal contraceptive patch 12. Male subjects must agree to refrain from sperm donation from the day of screening and for at least 90 days after the last dose of study drug. 13. Subject must be of generally good health as determined by the Investigator. 14. Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments.
Exclusion criteria
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, α1 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 within 21 days of the Baseline/Day 1 visit, this washout period does not apply to proton pump inhibitors, which can be taken up to 7 days before Day 1. 18. Known hypersensitivity to LDV, SOF or formulation excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of treatment with ledipasvir (LDV)/sofosbuvir (SOF) FDC (proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) using COBAS TaqMan Realtime PCR) | 12 weeks | 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 (SVR 12) using COBAS TaqMan Realtime PCR. |
| Safety and tolerability of LDV/SOF FDC-containing regimens (frequency of AEs and SAEs) | 24 weeks after treatment | 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 as measured by the frequency of AEs and SAEs assessed at end of treatment, 12 and 24 weeks after end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kinetics of circulating HCV RNA (mean viral load) | 24 weeks after treatment | To evaluate the kinetics of circulating HCV RNA measured as mean viral load during treatment (Baseline, week 2,4,6) and after treatment discontinuation (Follow up week 4, 12, 24) |
| Durability of response (proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) | 24 weeks after treatment | To determine the durability of response after discontinuation of therapy as measured by the proportion of subjects with sustained viral response (HCV RNA \< LLOQ TND) 24 weeks after discontinuation of therapy (SVR 24). |
| Emergence of viral resistance to LDV/SOF FDC | 24 weeks after treatment | To evaluate the emergence of viral resistance to LDV/SOF FDC during treatment and after treatment discontinuation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relationship between NK cell phenotype and function and treatment efficacy | 24 weeks after treatment | To assess any relationship between NK cell phenotype and function and treatment efficacy |
| Relationship between circulating serum chemokines and treatment efficacy and safety | 24 weeks after treatment | To assess any relationship between circulating serum chemokines and treatment efficacy and safety |
| HCV-specific T cell responses | 24 weeks after treatment | To assess any relationship between HCV-specific T cell responses and treatment efficacy |
Countries
Germany
Outcome results
None listed