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

NCT02309918 | Completed Phase 2

• 2 other identifiers: HepNet-aHCV-IV2013-001081-42
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 20

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.

Conditions

Acute Hepatitis C

Keywords

acute HCV Genotype 1 Infection; HCV RNA; LDV/SOF FDC

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Durability of response (proportion of subjects with sustained viral response (HCV RNA < LLOQ TND)

  24 weeks after treatment

• Kinetics of circulating HCV RNA (mean viral load)

  24 weeks after treatment

• Emergence of viral resistance to LDV/SOF FDC

  24 weeks after treatment

Other Outcomes (3)

• HCV-specific T cell responses

  24 weeks after treatment

• Relationship between NK cell phenotype and function and treatment efficacy

  24 weeks after treatment

• Relationship between circulating serum chemokines and treatment efficacy and safety

  24 weeks after treatment

Study Arms (1)

LDV/SOF FDC

OTHER

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

Drug: LDV/SOF FDC

Interventions

LDV/SOF FDC DRUG

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

LDV/SOF FDC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Male or female, age ≥ 18 years
• HCV RNA ≥ 103 IU/mL at Screening
• 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
• 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
• Non-cirrhotic. Absence of cirrhosis will be determined based on clinical parameters or ultrasound
• Body mass index (BMI) ≥ 18 kg/m2
• Screening ECG without clinically significant abnormalities
• Subjects must have the following laboratory parameters at screening:
• Hemoglobin ≥ 10 g/dL
• Platelets ≥ 90,000/µL
• INR ≤1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
• Albumin ≥ 3 g/dL
• HbA1c ≤ 10%

You may not qualify if:

• 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.
• Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug (for example, gastric bypass or severe ulcerative colitis).
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Clinical hepatic decompensation (i.e., clinical ascites, encephalopathy or variceal hemorrhage).
• Solid organ transplantation.
• Significant pulmonary disease or significant cardiac disease.
• 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.
• 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.
• Significant drug allergy (such as anaphylaxis or hepatotoxicity).
• Any prior treatment for HCV infection including prior exposure to any inhibitor of the NS5B and NS5A.
• Pregnant or nursing female or male with pregnant female partner
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, Wilson's disease, α1 antitrypsin deficiency, cholangitis)
• Infection with hepatitis B virus (HBV; defined as HBsAg-positive) or human immunodeficiency virus (HIV)
• Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent \> 10 mg/day)
• 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.

Sponsors & Collaborators

• HepNet Study House, German Liverfoundation: lead
• Hannover Medical School: collaborator
• Gilead Sciences: collaborator

Study Sites (20)

• Charite, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I

Bonn, 53105, Germany

Location

Medizinisches Versorgungszentrum

Düsseldorf, 40237, Germany

Location

• Universitätsklinikum Essen, Klinik für Gastroenterologie und Hepatologie

Essen, 45122, Germany

Location

Universitätsklinikum Frankfurt, Medizinische Klinik 1

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg, Klinik für Innere Medizin II, Gastroenterologie, Hepatologie, Endokrinologie und Infektiologie

Freiburg im Breisgau, 79106, Germany

Location

Ifi, Institut für Interdisziplinäre Medizin

Hamburg, 20099, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik und Poliklinik

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg, Gastroenterologie, Infektionen, Vergiftungen

Heidelberg, 69120, Germany

Location

Gastroenterologische Gemeinschaftspraxis Herne

Herne, 44623, Germany

Location

Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Klinik für Innere Medizin II - Gastroenterologie und Endokrinologie

Homburg, 66421, Germany

Location

Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin 1, Gastroenterologie, Hepatologie, Ernährungs- und Altersmedizin

Kiel, 24105, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Gastroenterologie und Rheumatologie

Leipzig, 4103, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Oberberg City München

München, 80331, Germany

Location

Klinikum rechts der Isar der TU-München, II. Medizinische Klinik und Poliklinik (Gastroenterologie)

München, 81675, Germany

Location

Medizinisches Versorgungszentrum Offenburg GmbH, St. Josefklinik, Ambulante Gastroenterologie

Offenburg, 77654, Germany

Location

Universitätsklinikum Tübingen, Innere Medizin I, Hepatologie, Gastroenterologie, Infektiologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg,Medizinische Klinik und Poliklinik II, Zentrum Innere Medizin

Würzburg, 97080, Germany

Location

Related 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, Zollner C, Zeuzem S, Papkalla A, Weber K, Hardtke S, von der Leyen H, Koch A, von Witzendorff D, Manns MP, Wedemeyer H; HepNet Acute HCV IV Study Group. Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study. Lancet Infect Dis. 2017 Feb;17(2):215-222. doi: 10.1016/S1473-3099(16)30408-X. Epub 2016 Oct 28.

  PMID: 28029529 RESULT

Study Officials

• Michael P. Manns, Prof. Dr.

  MHH, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Carl-Neuberg-Str. 1, 30625 Hannover, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: December 5, 2014
• Study Start: November 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 28, 2017

Record last verified: 2017-08

Locations

DE (20)