Trial document




drksid header

  DRKS00006863

Trial Description

start of 1:1-Block title

Title

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

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

HepNet Acute HCV IV

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

The Hepatitis C Virus (HCV) attacks the liver and leads to the liver disease Hepatitis C. The acute HCV infection may progress to a chronic liver disease remaining permanently in the patient`s body. Consequences of chronic infection include scarring of the liver or permanent liver damage. Therapies that have been used for treatment of the acute HCV infection may lead to serious side effects.
The objective of this study is to evaluate the efficacy and safety of treatment with ledipasvir/sofosbuvir FDC for 6 weeks in patients with acute genotype 1 HCV infection. All participating patients will be treated with the medication and monitored for further 24 weeks. Therefore patients need to visit the hospital/medical practitioner eight times for blood collection and clinical examinations.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

The exploratory objectives of this study are to assess any relationship between HCV-specific T cell responses and treatment efficacy as well as any relationship between NK cell phenotype and function and treatment efficacy. Additionally, any relationship between circulating serum chemokines and treatment efficacy and safety should be assed. Therefore serum/plasma and PBMC samples of every patient visit will be analysed immunologically.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00006863
  •   2014/10/31
  •   [---]*
  •   yes
  •   Approved
  •   6751M, Ethikkommission der Medizinischen Hochschule Hannover
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2013-001081-42 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   B17.1 -  Acute hepatitis C
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   LDV/SOF FDC is manufactured as a FDC tablet, consisting of 90 mg LDV (Ledipasvir) and 400 mg SOF (Sofosbuvir) for oral administration. Subjects will take 1 tablet once daily with or without food for 6 weeks.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- 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

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- 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

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2014/11/19
  •   20
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

1. Willing and able to provide written informed consent
2. Male or female, age ≥ 18 years
3. HCV RNA ≥ 10 3 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:
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
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.

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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 as described in Section 5.4 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

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Medizinische Hochschule Hannover
    • Mr. 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address other
    • Hannover Clinical Trial Center GmbHGilead Sciences Inc.
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • Medizinische Hochschule Hannover Klinik für Gastroenterologie, Hepatologie und Endokrinologie
    • Mr.  Prof. Dr.  Markus  Cornberg 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Deutsche LeberstiftungHepNet Study-House
    • Ms.  Dr.  Julia  Kahlhöfer 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Gilead Sciences Inc.
    • 333 Lakeside Drive
    • 94404  Foster City
    • United States
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
  • start of 1:1-Block address otherSupport
    • Deutsches Zentrum für Infektionsforschung
    • 30625  Hannover
    • Germany
    end of 1:1-Block address otherSupport
    start of 1:1-Block address contact otherSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact otherSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up complete
  •   2016/06/13
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  •   "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" im The Lancet Infectious Diseases 17 (2), S. 215–222. DOI: 10.1016/S1473-3099(16)30408-X. Katja Deterding; Christoph D Spinner; Eckart Schott; Tania M Welzel; Guido Gerken; Hartwig Klinker; Ulrich Spengler; Johannes Wiegand; Julian Schulze zur Wiesch; Anita Pathil; Markus Cornberg; Andreas Umgelter; Caroline Zöllner; Stefan Zeuzem; Armin Papkalla; Kristina Weber; Svenja Hardtke; Heiko von der Leyen; Armin Koch; Dorothee von Witzendorff; Michael P Manns; Heiner Wedemeyer; HepNet Acute HCV IV Study Group (2016).
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.