Telaprevir With Peginterferon Alfa & Ribavirin in Ex-People Who INject Drugs Infected by Genotype 1 Chronic Hepatitis C (INTEGRATE)

Observational Multicenter Study in Ex-People Who INject Drugs (Ex-PWIDs) to Evaluate Efficacy, Safety, and Adherence to TElaprevir in Combination With Pegylated Interferon Alfa and Ribavirin in Genotype 1 ChRonic HepATitis C PatiEnts

The purpose of this study is to collect information on the efficacy, safety and tolerability of telaprevir (in combination with other medications), in patients who have a history of intravenous drug use with genotype 1 chronic hepatitis C, under substitution therapy (eg., methadone, buprenorphine) and/or followed in addiction centres.

Study Overview

• Status: Completed
• Conditions: Hepatitis, Chronic

Detailed Description

This is a multicenter, non-interventional, observational, prospective study to evaluate the efficacy, safety, and adherence to telaprevir in ex-People Who Inject Drugs (ex-PWIDs) infected with genotype 1 chronic hepatitis C and any fibrosis stage including compensated cirrhosis, who are receiving substitution therapy (eg, methadone, buprenorphine) and/or are being followed in an addiction center. Patients may be treatment naïve or relapsers. Participating physicians are to offer enrollment in this study to all eligible patients at their site in who they plan to initiate triple therapy with telaprevir, pegylated interferon alfa (PegIFN alfa), and ribavirin (RBV). A target of 115 patients will participate in this study. The duration of each patient's participation in this study will be up to approximately 60 weeks. After obtaining the signed participation agreement or ICF, selection criteria will be reviewed to verify the patient's eligibility. Data will be recorded in the electronic case report form (CRF) at 6 time points for each patient which correspond to routine care visits: inclusion, and at the patient's routine care visit closest to Week 4, 12, and 24, end of treatment, and end-of-follow-up (e.g., approximately 12 weeks after end-of-treatment). No additional blood, urine, or other biological samples will be required, and no additional investigations, beyond the routine clinical management of the patient, will be performed.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
  • Brussels, Belgium
  • Bruxelles, Belgium
  • Genk, Belgium
  • Haine-Saint-Paul, Belgium
• France
  • Lomme, France
  • Montpellier, France
  • Perpignan Cedex, France
• Germany
  • Berlin, Germany
  • Biberach, Germany
  • Kassel, Germany
  • München, Germany
  • Münster, Germany
• Netherlands
  • Maastricht, Netherlands
• Switzerland
  • Lausanne, Switzerland
  • Zürich, Switzerland
• United Kingdom
  • Dundee, United Kingdom
  • London, United Kingdom
  • Nottingham, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Men or women who have HCV infection genotype 1, a quantifiable serum HCV RNA, documentation of the degree of liver fibrosis assessed by liver biopsy or non-invasive test (eg, fibrotest, fibroscan), physician decision to start triple therapy with telaprevir and PegIFN alfa/RBV, have never been treated with antiviral treatment (naïve) or who have relapsed after IFN or PegIFN plus RBV (relapsers), have a history of injecting drugs, and are currently under stable substitution therapy (eg, methadone, buprenorphine) and/or followed in an addiction center will be eligible to enter this study.

Description

Inclusion Criteria:

Have HCV genotype 1, a quantifiable serum HCV RNA, recent (within 18 months of baseline) documentation of the degree of liver fibrosis (Metavir F0-F4; Ishak 0-6) assessed by liver biopsy or non-invasive test (eg, fibrotest, fibroscan); Physician decision to start triple therapy with telaprevir and PegIFN alfa/RBV; Have never been treated with antiviral treatment (naïve) or who have relapsed after IFN or PegIFN plus RBV (relapsers); History of injecting drugs and are currently under stable substitution therapy (eg, methadone, buprenorphine) and/or followed in an addiction center.

Exclusion Criteria:

Infected or coinfected with HCV of a genotype other than genotype 1; Previous or current treatment with a DAA therapy; Have any contraindication specified in the SmPC for telaprevir, PegIFN alfa, or RBV; Have a history or other evidence of decompensated liver disease, or have coinfection with active hepatitis B or HIV; Currently participating in another investigational study or clinical study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virologic Response at 12 weeks (SVR12)	HCV RNA <25 IU/mL, at 12 weeks (SVR12) after the last dose of anti-HCV treatment (telaprevir, PegIFN alfa, RBV)	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adherence to telaprevir until Week 12	adherence as measured by pill count and/or patient questionnaire (modified medication adherence self-report inventory [M-MASRI]	week 12
adherence to PegIFN alfa and RBV	adherence as measured by pill/vial count and/or patient questionnaire (M-MASRI)	at end of treatment (week 24)
on-treatment virologic response undetectable	rapid virologic response [RVR] and extended rapid virologic response [eRVR], Week 12, end of treatment) based on viral load, as measured by HCV RNA <25 IU/mL undetectable	week 12 and end of treatment ()
on treatment virologic response	rapid virologic response [RVR] and extended rapid virologic response [eRVR], Week 12, end of treatment) based on viral load, as measured by HCV RNA <25 IU/mL	week 12 and end of treatment ()
health-related quality of life based on EQ-5D	The EQ-5D consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take 1 of 3 responses. The responses record 3 levels of severity (no problems/some or moderate problems/extreme problems). A standard vertical 20 cm visual analogue scale (similar to a thermometer) for recording an individual's rating for their current health-related quality of life state is also included ranging from 0 (worst imaginable health state) to 100 (best imaginable health state)	on day 1 and routine visits closest to week 4, 12, 24 and end of treatment and end of follow-up (up to approximately 60 weeks)
Hospital Anxiety and Depression Scale (HADS)	HADS is a validated 14-item scale with 7 of the items relating to anxiety and 7 relating to depression. Each item is scored from 0 to 3, with higher scores indicating greater likelihood of depression or anxiety. Cases of anxiety or depression are each defined by subscale scores of 8 or greater, and categorized as normal (score of 0-7), mild (score of 8-10), moderate (score of 11-14), and severe (score of 15-21). The recall period is the past week.	on day 1 and routine visits closest to week 4, 12, 24 and end of treatment and end of follow-up (up to approximately 60 weeks)
alcohol use disorders identification test (AUDIT)	The AUDIT questionnaire consists of 10 questions about a patient's quantity and frequency of alcohol use. The response to 8 of the questions are scored as 0 = never, 1 = monthly or less, 2 = 2 to 4 times a month, 3 = 2 to 3 times a week, 4 = 4 or more times a week. Two questions are scored as 0 = no, 2 = yes, but not in the last year, 4 = yes, during the last year. A score of 8 or more is associated with harmful or hazardous drinking	on day 1 and routine visits closest to week 4, 12, 24 and end of treatment and end of follow-up (up to approximately 60 weeks)

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium

Publications and helpful links

General Publications

• Robaeys G, Christensen S, Lucidarme D, Arain A, Bruggmann P, Kunkel J, Keim S, Jakel M, DeMasi R, Liu C, Lonjon-Domanec I, Foster GR. Chronic Hepatitis C Treatment in Patients with Drug Injection History: Findings of the INTEGRATE Prospective, Observational Study. Infect Dis Ther. 2017 Jun;6(2):265-275. doi: 10.1007/s40121-017-0158-x. Epub 2017 May 5.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (Estimate): November 8, 2013

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Liver Fibrosis; HCV genotype 1; ex-People who INject Drugs (ex-PWIDs)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: CR100966; VX-950HPC4017 (Other Identifier: Janssen Pharmaceutica NV - CTMS ID)