Ribavirin Dose Optimization for the Treatment of Hepatitis C

NCT ID: NCT01289496

Last Updated: 2014-02-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2013-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Hepatitis C

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Peg-interferon alpha-2a, Ribavirin

Intervention Type DRUG

* 4 weeks RBV priming;
* 24 or 48 weeks of Pegasys+Ribavirin (RBV) Treatment (depending on genotype);
* 24 weeks Follow-Up

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

Interventions

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Peg-interferon alpha-2a, Ribavirin

* 4 weeks RBV priming;
* 24 or 48 weeks of Pegasys+Ribavirin (RBV) Treatment (depending on genotype);
* 24 weeks Follow-Up

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

Intervention Type DRUG

Other Intervention Names

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Peg-interféron alpha-2a (PEGASYS) Ribavirin (COPEGUS)

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

OTHER

Sponsor Role collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Pierre Villeneuve, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

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Centre hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 12680884 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17118126 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18672540 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17253142 (View on PubMed)

Glue P. The clinical pharmacology of ribavirin. Semin Liver Dis. 1999;19 Suppl 1:17-24.

Reference Type BACKGROUND
PMID: 10349689 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15681898 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15812187 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18667516 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20399525 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11034261 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12386637 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19380853 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6175589 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18435468 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14749543 (View on PubMed)

Other Identifiers

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Control Number: 143155

Identifier Type: OTHER

Identifier Source: secondary_id

ML25553

Identifier Type: -

Identifier Source: org_study_id

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