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

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ClinicalTrials.gov Identifier: NCT02309918
Recruitment Status : Completed
First Posted : December 5, 2014
Last Update Posted : August 28, 2017
Sponsor:
Collaborators:
Hannover Medical School
Gilead Sciences
Information provided by (Responsible Party):
HepNet Study House, German Liverfoundation

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.

Condition or disease Intervention/treatment Phase
Acute Hepatitis C Drug: LDV/SOF FDC Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2014
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

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




Primary Outcome Measures :
  1. 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) [ Time Frame: 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.

  2. Safety and tolerability of LDV/SOF FDC-containing regimens (frequency of AEs and SAEs) [ Time Frame: 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 Outcome Measures :
  1. Durability of response (proportion of subjects with sustained viral response (HCV RNA < LLOQ TND) [ Time Frame: 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).

  2. Kinetics of circulating HCV RNA (mean viral load) [ Time Frame: 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)

  3. Emergence of viral resistance to LDV/SOF FDC [ Time Frame: 24 weeks after treatment ]
    To evaluate the emergence of viral resistance to LDV/SOF FDC during treatment and after treatment discontinuation


Other Outcome Measures:
  1. HCV-specific T cell responses [ Time Frame: 24 weeks after treatment ]
    To assess any relationship between HCV-specific T cell responses and treatment efficacy

  2. Relationship between NK cell phenotype and function and treatment efficacy [ Time Frame: 24 weeks after treatment ]
    To assess any relationship between NK cell phenotype and function and treatment efficacy

  3. Relationship between circulating serum chemokines and treatment efficacy and safety [ Time Frame: 24 weeks after treatment ]
    To assess any relationship between circulating serum chemokines and treatment efficacy and safety



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02309918


Locations
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Germany
• Charite, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie
Berlin, Germany, 13353
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I
Bonn, Germany, 53105
Medizinisches Versorgungszentrum
Düsseldorf, Germany, 40237
• Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie
Essen, Germany, 45122
Universitätsklinikum Frankfurt, Medizinische Klinik 1
Frankfurt, Germany, 60590
Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie
Freiburg, Germany, 79106
Ifi, Institut für Interdisziplinäre Medizin
Hamburg, Germany, 20099
Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik und Poliklinik
Hamburg, Germany, 20246
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
Hannover, Germany, 30625
Universitätsklinikum Heidelberg, Gastroenterologie, Infektionen, Vergiftungen
Heidelberg, Germany, 69120
Gastroenterologische Gemeinschaftspraxis Herne
Herne, Germany, 44623
Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Klinik für Innere Medizin II - Gastroenterologie und Endokrinologie
Homburg, Germany, 66421
Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin 1, Gastroenterologie, Hepatologie, Ernährungs- und Altersmedizin
Kiel, Germany, 24105
Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie
Leipzig, Germany, 4103
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik
Mainz, Germany, 55131
Oberberg City München
München, Germany, 80331
Klinikum rechts der Isar der TU-München, II. Medizinische Klinik und Poliklinik (Gastroenterologie)
München, Germany, 81675
Medizinisches Versorgungszentrum Offenburg GmbH, St. Josefklinik, Ambulante Gastroenterologie
Offenburg, Germany, 77654
Universitätsklinikum Tübingen, Innere Medizin I, Hepatologie, Gastroenterologie, Infektiologie
Tübingen, Germany, 72076
Universitätsklinikum Würzburg,Medizinische Klinik und Poliklinik II, Zentrum Innere Medizin
Würzburg, Germany, 97080
Sponsors and Collaborators
HepNet Study House, German Liverfoundation
Hannover Medical School
Gilead Sciences
Investigators
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Principal Investigator: Michael P. Manns, Prof. Dr. MHH, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

Publications of Results:
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Responsible Party: HepNet Study House, German Liverfoundation
ClinicalTrials.gov Identifier: NCT02309918     History of Changes
Other Study ID Numbers: HepNet-aHCV-IV
2013-001081-42 ( EudraCT Number )
First Posted: December 5, 2014    Key Record Dates
Last Update Posted: August 28, 2017
Last Verified: August 2017
Keywords provided by HepNet Study House, German Liverfoundation:
acute HCV Genotype 1 Infection
HCV RNA
LDV/SOF FDC
Additional relevant MeSH terms:
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Infection
Hepatitis A
Hepatitis C
Hepatitis
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Antiviral Agents
Anti-Infective Agents