- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01289496
Ribavirin Dose Optimization for the Treatment of Hepatitis C
Ribavirin Dose Optimization for the Treatment of Hepatitis C: A Pilot Study
Patients for whom treatment with peginterferon plus ribavirin was unsuccessful represent a category of patients for whom there is currently no worthwhile therapeutic alternative.
Several studies have shown that there is a relation between plasma ribavirin concentrations and treatment response. Adequate ribavirin plasma concentrations, especially during the first 12 weeks of treatment, should be associated with a better chance of response to the treatment.
The strategy for this study will be to use a loading dose of ribavirin before beginning the treatment with peg-interferon, thereby allowing for optimal ribavirin concentrations to be reached, and possibly improving the effectiveness of the treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Quebec
-
Montréal, Quebec, Canada, H2X1P1
- Centre Hospitalier de l'Université de Montréal
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age > 18 years
- Chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin (non-response: HCV-RNA decreased less than 2 logs after 3 months of treatment; relapse: HCV-RNA that becomes positive again after treatment is stopped
- Compensated hepatic disease (Child-Pugh ≤ 6)
- Provision by patient of his or her written consent
Exclusion Criteria:
- Females who are pregnant or lactating will be excluded
- Renal failure (estimated glomerular filtration rate < 50 ml/min)
- A contraindication to treatment with peginterferon plus ribavirin (uncontrolled psychiatric illness, pregnancy/nursing/non-use of effective contraceptive method, uncontrolled epilepsy for at least 6 months, heart failure, unstable angina, hemoglobin < 120 g/L, neutrophils < 1,000/mm3, platelets < 50 x 109/L, or any other condition that, in the investigator's opinion, contraindicates use of the treatment)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Peg-interferon alpha-2a, Ribavirin
Adult patients with chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin(non-response or relapse). This is a pilot study with no control group. |
Patients will receive PEGASYS® 180 µg in 0.5 mL (prefilled syringes) administered sc once weekly. Specific guidelines for adjusting the dose of PEGASYS® are provided in the product monograph.All PEGASYS® administrations will be via the sc route using sterile technique. Ribavirin 200 mg tablets
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) analysis assay
Time Frame: up to 24 weeks post treatment
|
Qualitative
|
up to 24 weeks post treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Viral Kinetics
Time Frame: up to 24 weeks post treatment
|
Plasma Ribavirin (RBV) Assays; Immune Response
|
up to 24 weeks post treatment
|
Neutrophils
Time Frame: up to 24-48 weeks of treatment
|
If neutrophils are < 500/mm, neupogen may be added
|
up to 24-48 weeks of treatment
|
Hemoglobin
Time Frame: up to 24-48 weeks of treatment
|
If hemoglobin is < 100g/L, erythropoietin and/or transfusions may be prescribed
|
up to 24-48 weeks of treatment
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jean-Pierre Villeneuve, M.D., Ph.D., Centre Hospitalier de l'Universite de Montreal (CHUM)
Publications and helpful links
General Publications
- Tsubota A, Hirose Y, Izumi N, Kumada H. Pharmacokinetics of ribavirin in combined interferon-alpha 2b and ribavirin therapy for chronic hepatitis C virus infection. Br J Clin Pharmacol. 2003 Apr;55(4):360-7. doi: 10.1046/j.1365-2125.2003.01780.x.
- Wade JR, Snoeck E, Duff F, Lamb M, Jorga K. Pharmacokinetics of ribavirin in patients with hepatitis C virus. Br J Clin Pharmacol. 2006 Dec;62(6):710-4. doi: 10.1111/j.1365-2125.2006.02704.x.
- Maynard M, Pradat P, Gagnieu MC, Souvignet C, Trepo C. Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients. Antivir Ther. 2008;13(4):607-11.
- Cheruvattath R, Rosati MJ, Gautam M, Vargas HE, Rakela J, Balan V. Pegylated interferon and ribavirin failures: is retreatment an option? Dig Dis Sci. 2007 Mar;52(3):732-6. doi: 10.1007/s10620-006-9457-x.
- Glue P. The clinical pharmacology of ribavirin. Semin Liver Dis. 1999;19 Suppl 1:17-24.
- Uchida M, Hamada A, Yamasaki M, Fujiyama S, Sasaki Y, Saito H. Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C. Drug Metab Pharmacokinet. 2004 Dec;19(6):438-43. doi: 10.2133/dmpk.19.438.
- Arase Y, Ikeda K, Tsubota A, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, Akuta N, Someya T, Hosaka T, Sezaki H, Kobayashi M, Kumada H. Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C. Intervirology. 2005;48(2-3):138-44. doi: 10.1159/000081741.
- Badr G, Bedard N, Abdel-Hakeem MS, Trautmann L, Willems B, Villeneuve JP, Haddad EK, Sekaly RP, Bruneau J, Shoukry NH. Early interferon therapy for hepatitis C virus infection rescues polyfunctional, long-lived CD8+ memory T cells. J Virol. 2008 Oct;82(20):10017-31. doi: 10.1128/JVI.01083-08. Epub 2008 Jul 30.
- Hofer H, Donnerer J, Sator K, Staufer K, Scherzer TM, Dejaco C, Sator M, Kessler H, Ferenci P. Seminal fluid ribavirin level and functional semen parameters in patients with chronic hepatitis C on antiviral combination therapy. J Hepatol. 2010 Jun;52(6):812-6. doi: 10.1016/j.jhep.2009.12.039. Epub 2010 Mar 23.
- Jen JF, Glue P, Gupta S, Zambas D, Hajian G. Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit. 2000 Oct;22(5):555-65. doi: 10.1097/00007691-200010000-00010.
- Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G. Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther. 2002 Oct;72(4):349-61. doi: 10.1067/mcp.2002.127112.
- Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandao-Mello CE, Reddy KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009 Apr 21;150(8):528-40. doi: 10.7326/0003-4819-150-8-200904210-00007.
- Kauppila A, Cantell K, Janne O, Kokko E, Vihko R. Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon. Int J Cancer. 1982 Mar 15;29(3):291-4. doi: 10.1002/ijc.2910290311.
- Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Cales P, Lefebvre A, Fauchais AL, Liozon E, Vidal E. Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology. 2008 May;47(5):1453-61. doi: 10.1002/hep.22217.
- Maeda Y, Kiribayashi Y, Moriya T, Maruhashi A, Omoda K, Funakoshi S, Murakami T, Takano M. Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C. Ther Drug Monit. 2004 Feb;26(1):9-15. doi: 10.1097/00007691-200402000-00004.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis C, Chronic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Ribavirin
- Peginterferon alfa-2a
- Interferon alpha-2
Other Study ID Numbers
- ML25553
- Control Number: 143155 (Other Identifier: Health Canada)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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