Telaprevir in Genotype 3 HCV

NCT02087111 | Completed Phase 4 DMC

• 3 other identifiers: 91322013-003729-2713/LO/1473
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief Summary

Patients with genotype 3 hepatitis C who have advanced liver disease (cirrhosis) have a very high chance of developing fatal complications of their disease unless they receive effective treatment. Unfortunately the best drugs that are currently available to treat genotype 3 hepatitis C (pegylated interferon and ribavirin) only work in about 50% of patients with advanced liver disease and therefore a large number of patients who have failed treatment are waiting for new, better drugs. Currently there are no treatments available for these patients. Telaprevir is a new drug that is licensed to treat genotype 1 hepatitis C and which works very well in these patients. In patients with genotype 3 hepatitis C small scale trials and laboratory studies show that some patients do respond quite well and others respond a little bit when given telaprevir. In patients who have exhausted all other treatment options the investigators speculate that telaprevir treatment may help some patients by clearing their infection. The purpose of this study is to see if telaprevir can help these patients and to determine if the investigators can predict in advance which people can be helped.

Conditions

Hepatitis C

Keywords

Telaprevir; Genotype 3 HCV

Outcome Measures

Primary Outcomes (1)

• Sustained virological response (SVR) 12 weeks after end of treatment (SVR12)

  To determine whether patients with genotype 3 HCV and cirrhosis who have relapsed following therapy with PegIFN and RBV will achieve a sustained virological response (SVR) if treated with telaprevir, PegIFN and RBV

  Week 36

Secondary Outcomes (3)

• Response rate prediction

  By week 12

• Sustained virological response 24 weeks after end of treatment.

  week 48

• Treatment Success

  After week 48

Study Arms (1)

Treatment

EXPERIMENTAL

All patients who are fulfil the entry criteria are treated for 24 weeks with 40 Kd Pegylated interferon alfa 2a, Ribavirin and 12 weeks with telaprevir.

Drug: Telaprevir; Drug: 40 Kd Pegylated interferon alfa 2a; Drug: Ribavirin

Interventions

Telaprevir DRUG

375 mg film coated tablets

Also known as: INCIVO

Treatment

40 Kd Pegylated interferon alfa 2a DRUG

180 µg in pre-filled syringe for sub-cutaneous injection

Also known as: Pegasys

Treatment

Ribavirin DRUG

200 mg tablets

Also known as: Copegus

Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age and ≤ 70 years old
• Advanced fibrosis - defined as a liver biopsy within 2 years showing an Ishak fibrosis score of \>4 OR radiological evidence of cirrhosis (ultrasound scan or fibroscan reading \>10.6)
• Previous therapy with pegylated interferon and ribavirin for at least 24 weeks with undetectable HCV RNA at the end of therapy and detectable HCV RNA six months after treatment cessation
• Chronic genotype 3 HCV infection, RNA positivity with genotype 3 infection confirmed at a local laboratory.
• HBsAg negative and no clinical evidence of co-infection with HIV
• Platelet count \>50,000 cells/mm3 (support with eltrombopag is permitted) Neutrophil count \> 600 cells/mm3
• All female patients of childbearing potential and all males with female partners of childbearing potential must be prepared to use two forms of effective contraception\* (combined) during treatment and 6 months after treatment end
• Able and willing to give informed consent and able to comply with study requirements

You may not qualify if:

• Evidence of other cause of significant liver disease - serum ferritin \> 1000, biochemical evidence of Wilson's disease, autoantibody titres in excess of 1:160
• Poorly controlled diabetes that, in the investigators opinion, precludes therapy
• Severe retinopathy that, in the opinion of the investigator, precludes therapy
• Evidence of ascites seen on previous liver ultrasound
• Haemoglobin concentration \<11 g/dL in females or \<12 g/dL in males or any patient with an increased risk for anaemia (e.g., thalassemia, sickle cell anaemia, spherocytosis, history of gastrointestinal bleeding) or for whom anaemia would be medically problematic
• Albumin levels \<35 G/L
• Females who are pregnant or breast-feeding
• History of severe psychiatric disease, including psychosis and/or depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease within the last 2 years
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis (defined as affecting \>10% of the body, where the palm of one hand equals 1%, or if the hands and feet are affected), rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management
• Other on-going serious medical condition in the opinion of the investigator that would prohibit treatment
• Poorly controlled thyroid dysfunction that, in the investigators opinion, precludes therapy
• History of major organ transplantation with an existing functional graft
• History of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous 6 months
• History or laboratory testing showing evidence of a haemoglobinopathy
• Concomitant administration with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These active substances include alfuzosin, amiodarone, bepridil, quinidine, astemizole, terfenadine, cisapride, pimozide, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), lovastatin, simvastatin, atorvastatin, sildenafil or tadalafil (only when used for treatment of pulmonary arterial hypertension) and orally administered midazolam or triazolam.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Janssen-Cilag Ltd.: collaborator
• Barts & The London NHS Trust: collaborator
• St George's Healthcare NHS Trust: collaborator
• Bradford Teaching Hospitals NHS Foundation Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator

Study Sites (4)

Bradford Teaching Hospitals NHS Foundation Trust

Bradford, BD9 6RJ, United Kingdom

Location

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

Ste Georges Healthcare NHS Trust

London, SW17 0QT, United Kingdom

Location

Nottingham University Hospitals Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (5)

• Shoeb D, Rowe IA, Freshwater D, Mutimer D, Brown A, Moreea S, Sood R, Marley R, Sabin CA, Foster GR. Response to antiviral therapy in patients with genotype 3 chronic hepatitis C: fibrosis but not race encourages relapse. Eur J Gastroenterol Hepatol. 2011 Sep;23(9):747-53. doi: 10.1097/MEG.0b013e3283488aba.

  PMID: 21691208 BACKGROUND

• Alazawi W, Cunningham M, Dearden J, Foster GR. Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection. Aliment Pharmacol Ther. 2010 Aug;32(3):344-55. doi: 10.1111/j.1365-2036.2010.04370.x. Epub 2010 May 22.

  PMID: 20497143 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

• Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A, Ferenci P, Nevens F, Mullhaupt B, Pockros P, Terg R, Shouval D, van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011 Jun 23;364(25):2417-28. doi: 10.1056/NEJMoa1013086.

  PMID: 21696308 BACKGROUND

• Foster GR, Hezode C, Bronowicki JP, Carosi G, Weiland O, Verlinden L, van Heeswijk R, van Baelen B, Picchio G, Beumont M. Telaprevir alone or with peginterferon and ribavirin reduces HCV RNA in patients with chronic genotype 2 but not genotype 3 infections. Gastroenterology. 2011 Sep;141(3):881-889.e1. doi: 10.1053/j.gastro.2011.05.046. Epub 2011 May 31.

  PMID: 21699786 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

telaprevir; peginterferon alfa-2a; Ribavirin

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

• Graham R Foster

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2014
• First Posted: March 14, 2014
• Study Start: April 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: January 5, 2023

Record last verified: 2014-07

Locations

GB (4)