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Trial record 98 of 382 for:    IFNA2 AND RBV AND genotype

Ribavirin Loading Dose or Priming and Concentration Targeting for HCV Genotype 1 (RibaC)

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ClinicalTrials.gov Identifier: NCT01226771
Recruitment Status : Completed
First Posted : October 22, 2010
Last Update Posted : March 24, 2015
Sponsor:
Collaborators:
The Swedish Research Council
Roche Pharma AG
Information provided by (Responsible Party):
Göteborg University

Tracking Information
First Submitted Date  ICMJE October 21, 2010
First Posted Date  ICMJE October 22, 2010
Last Update Posted Date March 24, 2015
Study Start Date  ICMJE September 2010
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2010)
The early virological response as measured by decline in HCV-RNA during the first 12 weeks of peginterferon alpha-2a and ribavirin therapy in the three study arms. [ Time Frame: The first 12 weeks of therapy ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01226771 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2010)
VRVR, RVR, cEVR, pEVR, SVR, and Relapse rates [ Time Frame: Throughout the treatment period including 24 weeks post completion of therapy ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ribavirin Loading Dose or Priming and Concentration Targeting for HCV Genotype 1
Official Title  ICMJE Not Provided
Brief Summary This is a randomized, open-label, parallel group, multicenter pilot study evaluating the efficacy and safety of alternative dosing of ribavirin vs. standard of care dosing in combination with peginterferon alpha-2a in interferon naïve patients with chronic hepatitis c genotype 1 infection.
Detailed Description The primary objective of the study is to demonstrate the efficacy and safety of (A) 2 weeks of high dose of ribavirin ("loading", ≥26 mg/kg/day for 14 days followed by ≥13 mg/kg/day) followed by concentration targeted (≥ 2.5 mg/L (10.25 μmol/L) 28 days after initiation of ribavirin therapy) dosing of ribavirin vs. (B) 4 weeks of ribavirin dosing before initiation of PEG-interferon dosing ("priming", ≥13 mg/kg/day) followed by concentration targeted (≥ 2.5 mg/L (10.25 μmol/L) 28 days after initiation of ribavirin therapy) dosing of ribavirin in combination with peginterferon alpha-2a in interferon naïve patients with chronic hepatitis C (CHC) virus genotype 1 infection as compared to (C) standard-of-care dosing of ribavirin (≥13 mg/kg/day without monitoring of ribavirin concentrations) in combination with peginterferon alpha-2a.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: Ribavirin "loading" dose given
    PEG-IFN α-2a 180 μg/week plus loading (≥26 mg/kg/day for 2 weeks followed by ≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 4 weeks of therapy) dosing of ribavirin and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks
  • Drug: "Priming" dose of ribavirin given
    Standard-of-care dosing of ribavirin (≥13 mg/kg/day) without PEG-IFN for 4 weeks followed by 24-48 additional weeks of PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 28 days after the initiation of ribavirin) dosing of ribavirin and response guided treatment duration (RVR 28 weeks, non-RVR 52 weeks, pEVR consider 76 weeks), follow-up period 24 weeks
  • Drug: Group C ("Standard-of-Care")
    PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day without any measurement of ribavirin concentration) and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks
Study Arms  ICMJE
  • Experimental: Group A ("Loading")
    PEG-IFN α-2a 180 μg/week plus loading (≥26 mg/kg/day for 2 weeks followed by ≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 4 weeks of therapy) dosing of ribavirin and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks
    Intervention: Drug: Ribavirin "loading" dose given
  • Experimental: Group B ("Priming")
    Standard-of-care dosing of ribavirin (≥13 mg/kg/day) without PEG-IFN for 4 weeks followed by 24-48 additional weeks of PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 28 days after the initiation of ribavirin) dosing of ribavirin and response guided treatment duration (RVR 28 weeks, non-RVR 52 weeks, pEVR consider 76 weeks), follow-up period 24 weeks
    Intervention: Drug: "Priming" dose of ribavirin given
  • Active Comparator: Group C ("Standard-of-Care)
    PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day without any measurement of ribavirin concentration) and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks
    Intervention: Drug: Group C ("Standard-of-Care")
Publications * Waldenström J, Westin J, Nyström K, Christensen P, Dalgard O, Färkkilä M, Lindahl K, Nilsson S, Norkrans G, Krarup H, Norrgren H, Rauning Buhl M, Stenmark S, Lagging M. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection. PLoS One. 2016 May 11;11(5):e0155142. doi: 10.1371/journal.pone.0155142. eCollection 2016.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2010)
105
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent
  • Male and female patients ≥18 years of age
  • Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
  • Serum HCV-RNA ≥15 IU/mL.
  • HCV genotype 1 infection confirmed within the past 2 years preceding the initiation of test drug dosing.
  • Compensated liver disease (Child-Pugh Grade A clinical classification)
  • Patients with cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP ≤100 ng/mL within 2 months of randomization
  • Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
  • All fertile males and females receiving ribavirin must be using effective contraception during treatment and during 4 months for female patients / 7 months for male patients after end of treatment
  • Subject must weigh between 45 and 105 kg at screening

Exclusion Criteria:

  • Women with ongoing pregnancy or breast feeding
  • IFN/ peg-interferon with or without ribavirin therapy at any previous time
  • Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) *6 months prior to the first dose of study drug
  • Any investigational drug ≤6 weeks prior to the first dose of study drug.
  • HCV genotype 2, 3, 4, 5, 6, or 7 infection.
  • Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab
  • Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
  • History or other evidence of decompensated liver disease
  • Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening
  • Serum creatinine level >2 mg/dl (>124 µmol/L) or creatinine clearance ≤50 ml/minute at screening
  • Severe psychiatric disease, especially depression, as judged by the treating physician.
  • History of a severe seizure disorder or current anticonvulsant use
  • History of immunologically mediated disease, severe chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
  • Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range)
  • Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
  • Evidence of drug abuse (including excessive alcohol consumption) in accordance with local therapeutic traditions.
  • Inability or unwillingness to provide informed consent or abide by the requirements of the study
  • Male partners of women who are pregnant
  • Ηemoglobin <12 g/dL in women or <13 g/dL in men at screening.
  • Any patient with an increased baseline risk for anemia (e.g. thalassemia major, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic coagulopathia.
  • Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
  • Evidence of allergy to PEG-IFN or ribavirin.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01226771
Other Study ID Numbers  ICMJE Eu-nr 2010-018332-41
2010-018332-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Göteborg University
Study Sponsor  ICMJE Göteborg University
Collaborators  ICMJE
  • The Swedish Research Council
  • Roche Pharma AG
Investigators  ICMJE Not Provided
PRS Account Göteborg University
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP