NCT01289496

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 25, 2011

Completed
7 days until next milestone

Study Start

First participant enrolled

February 1, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 3, 2011

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
Last Updated

February 26, 2014

Status Verified

August 1, 2012

Enrollment Period

2.5 years

First QC Date

January 25, 2011

Last Update Submit

February 24, 2014

Conditions

Chronic Hepatitis C

Keywords

RibavirinPegasysHepatitis

Outcome Measures

Primary Outcomes (1)

  • Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) analysis assay

    Qualitative

    up to 24 weeks post treatment

Secondary Outcomes (3)

  • Viral Kinetics

    up to 24 weeks post treatment

  • Neutrophils

    up to 24-48 weeks of treatment

  • Hemoglobin

    up to 24-48 weeks of treatment

Study Arms (1)

Peg-interferon alpha-2a, Ribavirin

EXPERIMENTAL

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.

Drug: Peg-interferon alpha-2a, Ribavirin

Interventions

Peg-interferon alpha-2a, RibavirinDRUG

* 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

Also known as: Peg-interféron alpha-2a (PEGASYS), Ribavirin (COPEGUS)
Peg-interferon alpha-2a, Ribavirin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X1P1, Canada

Location

Related Publications (15)

  • 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.

    PMID: 12680884BACKGROUND

  • 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.

    PMID: 17118126BACKGROUND

  • 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.

    PMID: 18672540BACKGROUND

  • 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.

    PMID: 17253142BACKGROUND

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

    PMID: 10349689BACKGROUND

  • 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.

    PMID: 15681898BACKGROUND

  • 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.

    PMID: 15812187BACKGROUND

  • 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.

    PMID: 18667516BACKGROUND

  • 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.

    PMID: 20399525BACKGROUND

  • 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.

    PMID: 11034261BACKGROUND

  • 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.

    PMID: 12386637BACKGROUND

  • 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.

    PMID: 19380853BACKGROUND

  • 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.

    PMID: 6175589BACKGROUND

  • 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.

    PMID: 18435468BACKGROUND

  • 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.

    PMID: 14749543BACKGROUND

MeSH Terms

Conditions

Hepatitis C, ChronicHepatitis

Interventions

Ribavirinpeginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

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

    Centre hospitalier de l'Université de Montréal (CHUM)

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

January 25, 2011

First Posted

February 3, 2011

Study Start

February 1, 2011

Primary Completion

August 1, 2013

Study Completion

August 1, 2013

Last Updated

February 26, 2014

Record last verified: 2012-08

Locations

CA(1)