HepNet Acute HCV IV - LDV/SOF FDC in Acute Genotype 1 Hepatitis C Virus Infection

Acute Hepatitis C Clinical Trial

Official title:

Interferon-free Treatment of Acute Genotype 1 Hepatitis C Virus Infection With Ledipasvir/Sofosbuvir Fixed-Dose Combination - The HepNet Acute HCV IV Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02309918
• Other study ID #: HepNet-aHCV-IV
• Secondary ID: 2013-001081-42
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2014
• Last updated: August 25, 2017
• Start date: November 2014
• Est. completion date: August 2016

Study information

• Verified date: August 2017
• Source: HepNet Study House, German Liverfoundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, 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 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

Related Conditions & MeSH terms

• Acute Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Infection
• Virus Diseases

Intervention

Drug:
• LDV/SOF FDC
Ledipasvir/Sofosbuvir fixed dose combination (FDC) tablet (LDV 90 mg/SOF 400 mg) once daily

Locations

Country	Name	City	State
Germany	• Charite, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie	Berlin
Germany	Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I	Bonn
Germany	Medizinisches Versorgungszentrum	Düsseldorf
Germany	• Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie	Essen
Germany	Universitätsklinikum Frankfurt, Medizinische Klinik 1	Frankfurt
Germany	Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie	Freiburg
Germany	Ifi, Institut für Interdisziplinäre Medizin	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik und Poliklinik	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie	Hannover
Germany	Universitätsklinikum Heidelberg, Gastroenterologie, Infektionen, Vergiftungen	Heidelberg
Germany	Gastroenterologische Gemeinschaftspraxis Herne	Herne
Germany	Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Klinik für Innere Medizin II - Gastroenterologie und Endokrinologie	Homburg
Germany	Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin 1, Gastroenterologie, Hepatologie, Ernährungs- und Altersmedizin	Kiel
Germany	Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik	Mainz
Germany	Klinikum rechts der Isar der TU-München, II. Medizinische Klinik und Poliklinik (Gastroenterologie)	München
Germany	Oberberg City München	München
Germany	Medizinisches Versorgungszentrum Offenburg GmbH, St. Josefklinik, Ambulante Gastroenterologie	Offenburg
Germany	Universitätsklinikum Tübingen, Innere Medizin I, Hepatologie, Gastroenterologie, Infektiologie	Tübingen
Germany	Universitätsklinikum Würzburg,Medizinische Klinik und Poliklinik II, Zentrum Innere Medizin	Würzburg

Sponsors (3)

Lead Sponsor	Collaborator
HepNet Study House, German Liverfoundation	Gilead Sciences, Hannover Clinical Trial Center GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Deterding K, Spinner CD, Schott E, Welzel TM, Gerken G, Klinker H, Spengler U, Wiegand J, Schulze Zur Wiesch J, Pathil A, Cornberg M, Umgelter A, Zöllner C, Zeuzem S, Papkalla A, Weber K, Hardtke S, von der Leyen H, Koch A, von Witzendorff D, Manns MP, We — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HCV-specific T cell responses	To assess any relationship between HCV-specific T cell responses and treatment efficacy	24 weeks after treatment
Other	Relationship between NK cell phenotype and function and treatment efficacy	To assess any relationship between NK cell phenotype and function and treatment efficacy	24 weeks after treatment
Other	Relationship between circulating serum chemokines and treatment efficacy and safety	To assess any relationship between circulating serum chemokines and treatment efficacy and safety	24 weeks after treatment
Primary	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)	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.	12 weeks
Primary	Safety and tolerability of LDV/SOF FDC-containing regimens (frequency of AEs and SAEs)	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.	24 weeks after treatment
Secondary	Durability of response (proportion of subjects with sustained viral response (HCV RNA < LLOQ TND)	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).	24 weeks after treatment
Secondary	Kinetics of circulating HCV RNA (mean viral load)	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)	24 weeks after treatment
Secondary	Emergence of viral resistance to LDV/SOF FDC	To evaluate the emergence of viral resistance to LDV/SOF FDC during treatment and after treatment discontinuation	24 weeks after treatment