A study to evaluate the safety and effectiveness of a quadruple drug regimen (VX-222, telaprevir, peginterferon alfa-2a and ribavirin) in treating chronic hepatitis C virus in subjects with cirrhosis who are treatment naive or nonresponders and relapsers to previous Peg-IFN/Ribavirin therapy.

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2011-004150-26-DE
• Date of registration: 03/01/2012
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals
• Public title: A study to evaluate the safety and effectiveness of a quadruple drug regimen (VX-222, telaprevir, peginterferon alfa-2a and ribavirin) in treating chronic hepatitis C virus in subjects with cirrhosis who are treatment naive or nonresponders and relapsers to previous Peg-IFN/Ribavirin therapy.
• Scientific title: A Multicenter, Open-Label, Phase 2b Pilot Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir, Peginterferon-Alfa-2 and Ribavirin) in Subjects With Genotype 1 Chronic Hepatitis C With Compensated Cirrhosis
• Date of first enrolment: 12/03/2012
• Target sample size: 114
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004150-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Canada, Germany, Poland, United Kingdom, United States

Contacts

• Name: Medical Information Center
• Affiliation: Vertex Pharmaceuticals Incorporated

• Name: Medical Information Center
• Affiliation: Vertex Pharmaceuticals Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
- Subjects (male and female, including those of childbearing potential) must be between the ages of 18 and 70 years
- Subjects must have genotype 1 CHC and laboratory evidence of HCV infection for at least 6 months before the Screening Visit
- Subjects must have documentation of compensated cirrhosis
- Subjects must fit one of the following categories:
• Treatment-naïve: never received treatment for hepatitis C
• Prior null responder: had <2-log10 decrease from baseline in HCV RNA concentration at the Week 12 assessment after prior Peg-IFN/RBV treatment of at least 12 weeks.
• Prior partial responder: had a =2-log10 decrease in HCV RNA concentration at the Week 12 assessment after prior Peg-IFN/RBV treatment of at least 12 weeks but never had undetectable HCV RNA levels while on treatment.
• Prior relapser: had undetectable HCV RNA at EOT after prior Peg-IFN/RBV treatment of at least 12 weeks but detectable HCV RNA after the end of prior treatment.
For null and partial responders, the Week 12 assessment of HCV RNA response used should be from a sample collected between no earlier than Week 11 and no later than Week 16. If more than one assessment from this time period is available, the assessment closest to Week 12 should be used.
The following information related to the virologic response to the last course of Peg IFN/RBV therapy, if applicable, must be available in the medical records of the subject:
• HCV RNA results before the start of treatment and at Week 12 assessment after start of treatment or documentation of the total treatment duration and log fold-change in HCV RNA.
• Last dose of prior therapy must be at least 12 weeks before first dose of study drug given under this protocol.
- Subject s must have plasma HCV RNA of =4.0 log10 IU/mL (10000 IU/mL).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 114
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Any previous treatment with an investigational drug or drug regimen for the treatment of hepatitis C, or previous treatment with an approved protease inhibitor
-History of any illness that, in the opinion of the investigator or general practitioner might confound the results of the study or pose an additional risk to the subject
- Any contraindication to Peg-IFN or RBV therapy, or history of severe AEs while on Peg-IFN or RBV
- Child-Pugh Score =7, or other clinical evidence of hepatic decompensation
- Any other cause of significant liver disease in addition to hepatitis C
- Diagnosed or suspected hepatocellular carcinoma
- History of organ transplant, with the exception of corneal transplants and skin grafts
- A medical condition that requires frequent or prolonged use of systemic corticosteroids or immunosuppressive drugs
- History of acute pancreatitis
- History or other clinical evidence of chronic pulmonary disease associated with functional impairment
- History of other evidence of sever retinopathy or clinically significant ophthalmological disorder
- History of illicit substance or alcohol abuse within 1 year before the Screening Visit
- Blood donation of approximately 1 pint (500 mL) within 56 days before dosing


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Chronic Hepatitis C Virus
MedDRA version: 14.1 Level: PT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: VX-222
Product Code: VX-222
Pharmaceutical Form: Tablet
CAS Number: 1026785-55-6
Current Sponsor code: VX-222
Other descriptive name: VCH-222, BCH-32222, C07062202-G
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: INCIVEK
Product Name: telaprevir
Product Code: VX-950
Pharmaceutical Form: Tablet
INN or Proposed INN: telaprevir
CAS Number: 402957-28-2
Current Sponsor code: VX-950
Other descriptive name: TELAPREVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 375-

Trade Name: Pegasys
Product Name: Pegasys
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: PEGINTERFERON ALFA-2A
CAS Number: 198153-51-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 180-

Trade Name: Copegus
Product Name: Copegus
Pharmaceutical Form: Tablet
INN or Proposed INN: RIBAVIRIN
CAS Number: 36791-04-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: To evaluate the antiviral efficacy of a quadruple drug regimen (VX-222, telaprevir, Peg-IFN and RBV) in subjects with genotype 1 CHC with compensated cirrhosis, who are treatment naive or were nonresponders (partial or null) or relapsers to previous Peg-IFN/RBV therapy.

Secondary Objective: To evaluate the safety and tolerability of the quadruple regimen in subjects with compensated cirrhosis
To assess the efficacy of quadruple regimen across interleukin-28B (IL-28B) genotypes
To characterize HCV variants in subjects on the quadruple regimen who have treatment failure
To characterize the pharmacokinetics (PK) of VX-222 and telaprevir in the quadruple regimen in subjects with compensated cirrhosis

Primary end point(s): The proportion of subjects who have an SVR (i.e., sustain an HCV RNA concentration below the lower limit of quantitation at 12 weeks after last planned dose of treatment (SVR12)

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Secondary end point(s): -The safety and tolerability as assessed by AEs, vital signs, 12-lead electrocardiograms (ECG), and laboratory assessments (serum chemistry, hematology, and urinalysis)
- Proportion of subjects who have an SVR24 weeks after the last planned dose of the study drug (SVR24)
- Proportion of subjects who achieve undetectable HCV RNA at Weeks 2,4,8, and 12 and -Proportion of subjects who have on-treatment virologic failure, defined as subjects who either meet a futility rule or complete assigned treatment duration and have detectable HCV RNA at the end of study drug treatment
- Proportion of subjects who relapse at end of treatment
- The association of IL-28B genotype with SVR12
- The amino acid sequence of the NS3 and NS5B proteins in subjects who have treatment failure
- VX-222, telaprevir, RBV plasma concentrations; and Peg-IFN serum concentrations

Timepoint(s) of evaluation of this end point: up to 52 weeks

Secondary ID(s)

VX11-222-106

Source(s) of Monetary Support

Vertex Pharmaceuticals