Peginterferon and Ribavirin, With or Without Telaprevir, for Genotype 1 Hepatitis C and IL28B CC Polymorphism

NCT01415141 | Withdrawn Phase 4

• 1 other identifier: M11-219
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic hepatitis C is a major cause of liver disease and is thus an important public health problem. Although some strains (genotypes) of the hepatitis C virus are highly responsive to treatment with a combination of peginterferon and ribavirin, the most common form of the virus (genotype 1) is relatively resistant to this treatment. Recently, telaprevir has been approved by the Food and Drug Administration to be given in combination with peginterferon and ribavirin. This 3-drug combination boosts the remission rate for genotype 1 hepatitis C to that seen with other more responsive hepatitis C genotypes treated with only peginterferon and ribavirin. However, telaprevir has additional side affects such as rash and anemia that may limit its usefulness. Intriguingly, about one third of patients infected with genotype 1 hepatitis C, who have a specific variation (polymorphism) in the DNA sequence (CC) near an immune response gene (IL28B), in fact are highly responsive to 2-drug treatment with peginterferon and ribavirin. This raises the possibility that individuals who have the IL28B CC polymorphism may not need to be treated with the addition of telaprevir and could therefore be spared unnecessary side effects. Thus, the purpose of this study is to determine among genotype 1 hepatitis C patients with the IL28B CC polymorphism the success rate and side effects of 3-drug treatment compared with 2-drug treatment. In this study, patients with genotype 1 chronic hepatitis C who have the IL28B CC polymorphism will be randomly assigned to be treated with telaprevir, peginterferon, and ribavirin or with only peginterferon with ribavirin. These medications and the procedures involved, including patient history, physical examination, and obtaining small volume blood specimens (less than 4 teaspoons) for laboratory testing, are within the scope of standard management of hepatitis C treatment. All patients will be monitored during treatment with periodic blood testing (weeks 2, 4, and every 4 weeks thereafter while on treatment, and 24 weeks after stopping treatment) and office visits (weeks 5, 12, 25, 49 while on treatment and 25 weeks after stopping treatment). The success of treatment will be judged by the presence or absence of detectable virus in blood, as measured by a sensitive diagnostic test (PCR). The data to be generated will include measurement by PCR of hepatitis C viral loads before, during, and after treatment, as well as reporting of adverse drug effects.

Conditions

Hepatitis C

Keywords

genotype 1; IL28B CC polymorphism; telaprevir; peginterferon; ribavirin

Outcome Measures

Primary Outcomes (1)

• Sustained virological response among subjects receiving a three drug versus two drug regimen of treatment

  Sustained virological response is defined as undetectable hepatitis C virus RNA in the blood at 24 weeks after the completion of antiviral treatment. This will be measured by PCR to determine the hepatitis C viral load in blood at the indicated time point.

  24 weeks after completion of treatment

Secondary Outcomes (1)

• Extended rapid virological response in patients receiving three drug versus two drug regimen

  weeks 4 and 12 of treatment

Study Arms (2)

PR

ACTIVE COMPARATOR

Treatment with Peginterferon and Ribavirin for up to 48 weeks Those who achieve eRVR will receive 24 weeks of treatment

Drug: Peginterferon alfa-2a; Drug: Ribavirin

TPR

ACTIVE COMPARATOR

Treatment with Telaprevir, Peginterferon and Ribavirin. Patients will receive all 3 drugs for 12 weeks then switch to Peginterferon and Ribavirin for 36 weeks Those who achieve eRVR will receive 12 weeks of treatment with all 3 drugs and then 12 weeks of treatment with the 2 drugs.

Drug: Peginterferon alfa-2a; Drug: Ribavirin; Drug: telaprevir

Interventions

Peginterferon alfa-2a DRUG

180ug subcutaneously, weekly

PR; TPR

Ribavirin DRUG

Administered orally twice a day as follows: weight \< 75kg - 1000mg weight ≥ 75kg - 1200mg

PR; TPR

telaprevir DRUG

750mg every 8 hours, orally

TPR

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Serum Hepatitis C RNA \> 10,000IU/mL
• Hepatitis C virus genotype 1
• IL28B polymorphism

You may not qualify if:

• Previous treatment for chronic Hepatitis C
• clinical or biological evidence of acute hepatitis, including serum ALT or AST \> 300U/ml
• HIV antibody positive, hepatitis b surface antigen positive or known diagnosis of other chronic liver disease
• Contraindications to PR-based treatment:
• uncontrolled psychiatric illness
• active substance dependency
• Known autoimmune disorder
• Untreated thyroid disease
• Uncontrolled seizure disorder
• Pregnancy, lactation or inability to maintain contraception
• Chronic kidney disease w/ estimated GFR\< 60
• ANC\<1.5/nl, Hb\<12g/dl, or platelets\<75/nl
• Clinical or biochemical evidence of decompensated liver disease including:
• History of encephalopathy, ascites, or variceal bleeding OR
• Bilirubin \> 3g/dl or INR \> 1.5

Sponsors & Collaborators

• University of Vermont: lead

Study Sites (2)

Emory University School of Medicine

Atlanta, Georgia, 30030, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Related Publications (6)

• Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010 Feb;138(2):513-21, 521.e1-6. doi: 10.1053/j.gastro.2009.09.067. Epub 2009 Oct 25.

  PMID: 19861128 BACKGROUND

• Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006 Dec 7;355(23):2444-51. doi: 10.1056/NEJMct061675. No abstract available.

  PMID: 17151366 BACKGROUND

• Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, Vinelli F, Scotto G, Montalto G, Romano M, Cristofaro G, Mottola L, Spirito F, Andriulli A. Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial. Hepatology. 2008 Jan;47(1):43-50. doi: 10.1002/hep.22061.

  PMID: 18069698 BACKGROUND

• Seeff LB, Ghany MG. Management of untreated and nonresponder patients with chronic hepatitis C. Semin Liver Dis. 2010 Nov;30(4):348-60. doi: 10.1055/s-0030-1267536. Epub 2010 Oct 19.

  PMID: 20960375 BACKGROUND

• Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010 Jul;139(1):120-9.e18. doi: 10.1053/j.gastro.2010.04.013. Epub 2010 Apr 24.

  PMID: 20399780 BACKGROUND

• Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011 Jun 23;364(25):2405-16. doi: 10.1056/NEJMoa1012912.

  PMID: 21696307 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

peginterferon alfa-2a; Ribavirin; telaprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Steven Lidofsky, MD

  University of Vermont & Fletcher Allen Health Care

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 11, 2011
• Study Start: July 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (2)