EXtended Therapy in Hepatitis C Genotype 3 Infected Patients

NCT01095445 | Terminated Phase 3 DMC

• 1 other identifier: EXACT-R(3)
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to evaluate the effect of 48 vs 24 weeks of treatment with Peginterferon alfa-2b plus weight-based ribavirin on Sustained Virologic Response (SVR) and relapse rates in patients infected with genotype 3 chronic hepatitis C (CHC) who do not achieve a Rapid Virologic Response (RVR) but attain a complete Early Virologic Response (cEVR).

Conditions

Chronic Hepatitis C

Keywords

hepatitis C; genotype 3; end of treatment response; relapse rate; rapid virologic response; complete early virologic response

Outcome Measures

Primary Outcomes (1)

• End of treatment response

  Undetectable hepatitis C virus (HCV) RNA at 24 weeks following end of therapy

  24 weeks following end of therapy

Secondary Outcomes (1)

• Relapse rate

  24 weeks following end of therapy

Study Arms (2)

Standard of care treatment

NO INTERVENTION

Participants will be randomized to receive only the standard 24 weeks of therapy (Peginterferon alfa-2b plus ribavirin).

Extended therapy

ACTIVE COMPARATOR

Participants will be randomized to receive 24 weeks of therapy (Peginterferon alfa-2b plus ribavirin) in addition to their standard of care therapy.

Drug: Peginterferon alfa-2b (Pegetron) plus ribavirin (Rebetol)

Interventions

Peginterferon alfa-2b (Pegetron) plus ribavirin (Rebetol) DRUG

Dosage Form: Pegetron - powder for solution; Rebetol - capsules Strength: Pegetron Redipen - 120 mcg per pen; Rebetol - 200 mg Route of Administration: Pegetron - subcutaneous; Rebetol - oral

Also known as: Pegetron, Rebetol

Extended therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Infected with only genotype 3, hepatitis C
• Treatment naïve before current course of therapy
• A positive HCV RNA test result at Week 4 (no RVR)
• A negative HCV RNA test result at Week 12 (cEVR)
• A recent liver biopsy (within 3 years prior to study entry) is required. If the patient has either liver biopsy proven cirrhosis in the past or has splenomegaly with features of cirrhosis on ultrasound and/or thrombocytopenia (\<150x109/ml) at any time in the past or has a Fibroscan reading of 10 or above or has a Fibrotest score of 0.75 or above (equivalent to F3 on the METAVIR scale), a biopsy will not be required. A copy of the latest report must be available.

You may not qualify if:

• Under age 18
• Co-infection with HIV or Hepatitis B or any other HCV genotype in addition to genotype 3
• Prior treatment for Hepatitis C aside from herbal remedies
• Evidence of decompensated liver disease, such as ascites, bleeding varices, hepatic encephalopathy or jaundice (conjugated hyperbilirubinemia)
• INR \> 1.3 at baseline
• Platelet count \<70 X 109/μl at baseline
• Those subjects with diabetes and/or systemic hypertension will need to have ocular examinations (as per standard of care \[SOC\]) prior to treatment and will be excluded if they are found to have a diabetic retinopathy, optic nerve disorders, retinal hemorrhage or any other clinically significant abnormality
• Pre-existing psychiatric conditions including:
• Current moderate or severe depression despite appropriate therapy.
• Active suicidal ideation or previous attempt at suicide
• Patients with a history of severe psychiatric disorder (may be included if so desired by the investigator but pretreatment psychiatric evaluation is required (SOC)).
• Clinical diagnosis of current substance abuse: Alcohol (\>40g/d), injection drugs, inhalational drugs (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over the counter drugs within one year of the screening visit.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Schering-Plough: collaborator

Study Sites (12)

Calgary Heart Centre

Calgary, Alberta, T2N 4Z6, Canada

Location

Hys Med Centre

Edmonton, Alberta, T2N 4Z6, Canada

Location

Liver and Intestinal Research Centre

Vancouver, British Columbia, V5Z 1H2, Canada

Location

Dr. John D Farley Medical Office

Vancouver, British Columbia, V6A 4B6, Canada

Location

Pacific Gastroenterology Assoc

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Hotel Dieu Hospital

Kingston, Ontario, K7L 5G2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

Dr. Dalia El-Ashry clinic

Mississauga, Ontario, L5B 2V2, Canada

Location

Credit Valley Med Arts Centre

Mississauga, Ontario, L5M2V8, Canada

Location

Toronto General Hospital - Dr. M. Sherman

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Western Hospital - Liver Clinic

Toronto, Ontario, M5T 2S8, Canada

Location

SMBD Jewish Gen Hosp

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (24)

• Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55. doi: 10.7326/0003-4819-140-5-200403020-00010.

  PMID: 14996676 BACKGROUND

• Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004 Jun;40(6):993-9. doi: 10.1016/j.jhep.2004.02.007.

  PMID: 15158341 BACKGROUND

• Powis J, Peltekian KM, Lee SS, Sherman M, Bain VG, Cooper C, Krajden M, Deschenes M, Balshaw RF, Heathcote EJ, Yoshida EM; Canadian Pegasys Study Group. Exploring differences in response to treatment with peginterferon alpha 2a (40kD) and ribavirin in chronic hepatitis C between genotypes 2 and 3. J Viral Hepat. 2008 Jan;15(1):52-7. doi: 10.1111/j.1365-2893.2007.00889.x.

  PMID: 18088245 BACKGROUND

• Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004 Dec;40(6):1260-5. doi: 10.1002/hep.20467.

  PMID: 15558712 BACKGROUND

• Lagging M, Langeland N, Pedersen C, Farkkila M, Buhl MR, Morch K, Dhillon AP, Alsio A, Hellstrand K, Westin J, Norkrans G; NORDynamIC Study Group. Randomized comparison of 12 or 24 weeks of peginterferon alpha-2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection. Hepatology. 2008 Jun;47(6):1837-45. doi: 10.1002/hep.22253.

  PMID: 18454508 BACKGROUND

• Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17. doi: 10.1056/NEJMoa042608.

  PMID: 15972867 BACKGROUND

• Dalgard O, Bjoro K, Ring-Larsen H, Bjornsson E, Holberg-Petersen M, Skovlund E, Reichard O, Myrvang B, Sundelof B, Ritland S, Hellum K, Fryden A, Florholmen J, Verbaan H; North-C Group. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology. 2008 Jan;47(1):35-42. doi: 10.1002/hep.21975.

  PMID: 17975791 BACKGROUND

• Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, Shafran SD, Barange K, Lin A, Soman A, Zeuzem S; ACCELERATE Investigators. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34. doi: 10.1056/NEJMoa066403.

  PMID: 17625124 BACKGROUND

• Bain VG, Kaita KD, Marotta P, Yoshida EM, Swain MG, Bailey RJ, Patel K, Cronin PW, Pulkstenis E, McHutchison JG, Subramanian GM. Safety and antiviral activity of albinterferon alfa-2b dosed every four weeks in genotype 2/3 chronic hepatitis C patients. Clin Gastroenterol Hepatol. 2008 Jun;6(6):701-6. doi: 10.1016/j.cgh.2008.02.056. Epub 2008 May 7.

  PMID: 18467185 BACKGROUND

• Vigani AG, Pavan MH, Tozzo R, Goncales ES, Feltrin A, Fais VC, Lazarini MS, Goncales NS, Goncales FL Jr. Comparative study of patients with chronic hepatitis C virus infection due to genotypes 1 and 3 referred for treatment in southeast Brazil. BMC Infect Dis. 2008 Dec 4;8:164. doi: 10.1186/1471-2334-8-164.

  PMID: 19055835 BACKGROUND

• Mangia A, Minerva N, Bacca D, Cozzolongo R, Agostinacchio E, Sogari F, Scotto G, Vinelli F, Ricci GL, Romano M, Carretta V, Petruzzellis D, Andriulli A. Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection. Hepatology. 2009 Feb;49(2):358-63. doi: 10.1002/hep.22679.

  PMID: 19072829 BACKGROUND

• Farooqi JI, Farooqi RJ. Conventional interferon alfa-2b and ribavirin for 12 versus 24 weeks in HCV genotype 2 or 3. J Coll Physicians Surg Pak. 2008 Oct;18(10):620-4. doi: 10.2008/JCPSP.620624.

  PMID: 18940119 BACKGROUND

• von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Haussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005 Aug;129(2):522-7. doi: 10.1016/j.gastro.2005.05.008.

  PMID: 16083709 BACKGROUND

• Veldt BJ, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Intern Med. 2007 Nov 20;147(10):677-84. doi: 10.7326/0003-4819-147-10-200711200-00003.

  PMID: 18025443 BACKGROUND

• Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, Szklo M, Thomas DL. Hepatitis C virus infection and incident type 2 diabetes. Hepatology. 2003 Jul;38(1):50-6. doi: 10.1053/jhep.2003.50291.

  PMID: 12829986 BACKGROUND

• Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, Sobesky R, Martinot-Peignoux M, Maylin S, Nicolas-Chanoine MH, Paradis V, Vidaud M, Valla D, Bedossa P, Marcellin P. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008 Feb;134(2):416-23. doi: 10.1053/j.gastro.2007.11.010. Epub 2007 Nov 12.

  PMID: 18164296 BACKGROUND

• Everhart JE, Lok AS, Kim HY, Morgan TR, Lindsay KL, Chung RT, Bonkovsky HL, Ghany MG; HALT-C Trial Group. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009 Aug;137(2):549-57. doi: 10.1053/j.gastro.2009.05.007. Epub 2009 May 13.

  PMID: 19445938 BACKGROUND

• Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005 Mar;128(3):636-41. doi: 10.1053/j.gastro.2004.12.049.

  PMID: 15765399 BACKGROUND

• Mathias RA, Deepa M, Deepa R, Wilson AF, Mohan V. Heritability of quantitative traits associated with type 2 diabetes mellitus in large multiplex families from South India. Metabolism. 2009 Oct;58(10):1439-45. doi: 10.1016/j.metabol.2009.04.041. Epub 2009 Jul 1.

  PMID: 19570552 BACKGROUND

• Arase Y, Suzuki F, Suzuki Y, Akuta N, Kobayashi M, Kawamura Y, Yatsuji H, Sezaki H, Hosaka T, Hirakawa M, Ikeda K, Kumada H. Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C. Hepatology. 2009 Mar;49(3):739-44. doi: 10.1002/hep.22703.

  PMID: 19127513 BACKGROUND

• Idrees M, Riazuddin S. Frequency distribution of hepatitis C virus genotypes in different geographical regions of Pakistan and their possible routes of transmission. BMC Infect Dis. 2008 May 23;8:69. doi: 10.1186/1471-2334-8-69.

  PMID: 18498666 BACKGROUND

• Peng JS, Wang X, Liu MQ, Zhou DJ, Gong J, Xu HM, Chen JP, Zhu HH, Zhou W, Ho WZ. Genetic variation of hepatitis C virus in a cohort of injection heroin users in Wuhan, China. Virus Res. 2008 Jul;135(1):191-6. doi: 10.1016/j.virusres.2008.01.017. Epub 2008 Mar 18.

  PMID: 18353479 BACKGROUND

• Pearlman BL, Ehleben C, Saifee S. Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology. 2007 Dec;46(6):1688-94. doi: 10.1002/hep.21919.

  PMID: 18046717 BACKGROUND

• Sherman M, Shafran S, Burak K, Doucette K, Wong W, Girgrah N, Yoshida E, Renner E, Wong P, Deschenes M. Management of chronic hepatitis C: consensus guidelines. Can J Gastroenterol. 2007 Jun;21 Suppl C(Suppl C):25C-34C.

  PMID: 17568824 BACKGROUND

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• E. Jenny Heathcote, MB,BS,MD,FRCP,FRCP(C)

  University Health Network - Toronto Western Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: March 30, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 29, 2011

Record last verified: 2010-03

Locations

CA (12)