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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01080222




Registration number
NCT01080222
Ethics application status
Date submitted
1/03/2010
Date registered
4/03/2010
Date last updated
30/09/2020

Titles & IDs
Public title
A Safety and Efficacy Study of the Combination of VX-222 and Telaprevir in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus Infection
Scientific title
A Randomized, Parallel-Group, Dose-Ranging Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Antiviral Activity of VX-222 and Telaprevir in Combination With and Without Peginterferon-Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C
Secondary ID [1] 0 0
VX09-222-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis C Virus Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - telaprevir
Treatment: Drugs - VX-222
Treatment: Drugs - ribavirin
Treatment: Other - peginterferon-alfa-2a
Treatment: Drugs - VX-222

Experimental: Treatment Arm A - Treatment Arm A was discontinued as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing.

Experimental: Treatment Arm B - Treatment Arm B was discontinued as a result of patients meeting a pre-defined stopping rule relating to viral breakthrough.

Experimental: Treatment Arm C - * Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks.
* Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks.
* Enrollment for this arm is complete. No additional subjects will be recruited.

Experimental: Treatment Arm D - * Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks.
* Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks.
* Enrollment for this arm is complete. No additional subjects will be recruited.

Experimental: Treatment Arm E - * Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks.
* Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks.

Experimental: Treatment Arm F - * Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks.
* Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks.


Treatment: Drugs: telaprevir
tablet, 1125-mg, twice daily

Treatment: Drugs: VX-222
capsule, 100-mg, twice daily

Treatment: Drugs: ribavirin
tablet, 1000-mg for subjects weighing \<75-kg or 1200-mg for subjects weighing =75-kg, twice daily

Treatment: Other: peginterferon-alfa-2a
subcutaneous injection, 180-mcg, once weekly

Treatment: Drugs: VX-222
capsule, 400-mg, twice daily
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and Tolerability
Timepoint [1] 0 0
40 weeks
Secondary outcome [1] 0 0
Proportion of Subjects Who Achieve a Sustained Viral Response
Timepoint [1] 0 0
24 weeks after the completion of the last dose of the assigned study drug treatment regimen
Secondary outcome [2] 0 0
Undetectable HCV RNA Measurements
Timepoint [2] 0 0
36 weeks
Secondary outcome [3] 0 0
Proportion of Subjects Who Have a Viral Breakthrough or Relapse
Timepoint [3] 0 0
60 weeks
Secondary outcome [4] 0 0
Plasma Exposures of VX-222 and Telaprevir
Timepoint [4] 0 0
12 weeks

Eligibility
Key inclusion criteria
* Males and females of non-childbearing potential
* Genotype 1 chronic hepatitis C
* Laboratory evidence of HCV infection for 6 months
* Histologic evidence of chronic hepatitis C
* Subjects who have a body mass index (BMI) of =35 kg/m² (BMI = weight in kg / height² in meters)
* Treatment Arm E: This arm will enroll only subjects infected with HCV genotype 1b virus
* Treatment Arm F: This arm will enroll only subjects infected with HCV genotype 1a virus
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects who have received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C
* Subjects with any contraindications to peginterferon alfa-2a and/or ribavirin
* Subjects with any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to malignancy with hepatic involvement, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis
* Histologic evidence of hepatic cirrhosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2013
Sample size
Target
Accrual to date
Final
152
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Rhode Island
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
New Zealand
State/province [16] 0 0
Auckland
Country [17] 0 0
New Zealand
State/province [17] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the safety and efficacy of combination treatment with VX-222 and telaprevir administered for 12 weeks with and without peginterferon-alfa-2a and/or ribavirin. The subjects enrolled in this study are chronically infected with hepatitis C virus (HCV) genotype 1 and will not have previously received treatment for their HCV infection.

This study will include an Investigational Phase and Extension Phase. These phases will contain a Treatment Period and a Follow-up Period. All subjects will be enrolled in the Investigational Phase of this study. Subjects who fail treatment during the Investigational Phase will have the option to enter the Extension Phase at which point they will be eligible to receive peginterferon alfa-2a and ribavirin for a total of 48 weeks.

Based on an evaluation of on-treatment safety, pharmacokinetic and antiviral data from patients in each arm of the trial, Vertex may elect to enroll up to two additional treatment arms (Treatment Arm E and Treatment Arm F) that will evaluate telaprevir/VX-222-based combination therapy. The components of the treatment regimens of these arms will be selected based on clinical data that emerges from the four initially-studied regimens. If enacted, up to 25 patients are expected to enroll in each additional treatment arm.

If Treatment Arm E or Treatment Arm F is discontinued subjects meeting certain criteria will have the option to enter a telaprevir-containing Rollover Phase. Subjects who do not meet the eligibility criteria to enter the Rollover Phase may elect to enter the Extension Phase.
Trial website
https://clinicaltrials.gov/study/NCT01080222
Trial related presentations / publications
Jiang M, Zhang EZ, Ardzinski A, Tigges A, Davis A, Sullivan JC, Nelson M, Spanks J, Dorrian J, Nicolas O, Bartels DJ, Rao BG, Rijnbrand R, Kieffer TL. Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor. Antimicrob Agents Chemother. 2014 Sep;58(9):5456-65. doi: 10.1128/AAC.03052-14. Epub 2014 Jun 30.
Di Bisceglie AM, Sulkowski M, Gane E, Jacobson IM, Nelson D, DeSouza C, Alves K, George S, Kieffer T, Zhang EZ, Kauffman R, Asmal M, Koziel MJ. VX-222, a non-nucleoside NS5B polymerase inhibitor, in telaprevir-based regimens for genotype 1 hepatitis C virus infection. Eur J Gastroenterol Hepatol. 2014 Jul;26(7):761-73. doi: 10.1097/MEG.0000000000000084.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Vertex Pharmaceuticals Incorporated
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01080222