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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01289782




Registration number
NCT01289782
Ethics application status
Date submitted
7/01/2011
Date registered
4/02/2011
Date last updated
4/06/2014

Titles & IDs
Public title
An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon a-2a and Ribavirin in Treatment-naïve, Genotype 1 Hepatitis Cinfected Subjects
Secondary ID [1] 0 0
TMC435-TiDP16-C208
Secondary ID [2] 0 0
CR017386
Universal Trial Number (UTN)
Trial acronym
QUEST-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Condition category
Condition code
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 - Placebo
Treatment: Drugs - TMC435
Treatment: Drugs - Peginterferon alpha-2a (PegIFN alpha-2a)
Treatment: Drugs - Ribavirin (RBV)

Experimental: TMC435 - TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 24 or 48 weeks

Placebo comparator: Placebo - Placebo 150 mg capsule once daily for 12 weeks in addition to PegIFNa-2a and RBV for 48 weeks


Treatment: Drugs: Placebo
150 mg capsule once daily for 12 weeks in addition to PegIFN alpha-2a and RBV for 48 weeks

Treatment: Drugs: TMC435
150 mg capsule once daily for 12 weeks in addition to PegIFN alpha-2a and RBV for 24 or 48 weeks

Treatment: Drugs: Peginterferon alpha-2a (PegIFN alpha-2a)
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.

Treatment: Drugs: Ribavirin (RBV)
200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Timepoint [1] 0 0
Week 36 or Week 60
Secondary outcome [1] 0 0
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Timepoint [1] 0 0
Week 72
Secondary outcome [2] 0 0
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Timepoint [2] 0 0
Week 48 or Week 72
Secondary outcome [3] 0 0
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
Timepoint [3] 0 0
Week 28 or Week 52
Secondary outcome [4] 0 0
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Timepoint [4] 0 0
Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Secondary outcome [5] 0 0
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Timepoint [5] 0 0
Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
Secondary outcome [6] 0 0
Percentage of Participants With On-treatment Virologic Response at All Time Points
Timepoint [6] 0 0
Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
Secondary outcome [7] 0 0
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Timepoint [7] 0 0
Week 4
Secondary outcome [8] 0 0
The Percentage of Participants Achieving a Early Virologic Response (EVR)
Timepoint [8] 0 0
Week 12
Secondary outcome [9] 0 0
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Timepoint [9] 0 0
Week 12
Secondary outcome [10] 0 0
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
Timepoint [10] 0 0
Week 4 and 12
Secondary outcome [11] 0 0
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
Timepoint [11] 0 0
Week 4
Secondary outcome [12] 0 0
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
Timepoint [12] 0 0
Week 4
Secondary outcome [13] 0 0
Percentage of Participants With Null Response
Timepoint [13] 0 0
Week 12
Secondary outcome [14] 0 0
Percentage of Participants With Partial Response
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
Percentage of Participants With Viral Breakthrough
Timepoint [15] 0 0
Up to Week 48
Secondary outcome [16] 0 0
Percentage of Participants With Viral Relapse
Timepoint [16] 0 0
Up to Week 72
Secondary outcome [17] 0 0
Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
Timepoint [17] 0 0
Week 24
Secondary outcome [18] 0 0
Percentage of Participants With On-treatment Failure
Timepoint [18] 0 0
Week 48
Secondary outcome [19] 0 0
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
Timepoint [19] 0 0
Up to Week 48
Secondary outcome [20] 0 0
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
Timepoint [20] 0 0
Up to Week 48
Secondary outcome [21] 0 0
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
Timepoint [21] 0 0
Up to Week 48
Secondary outcome [22] 0 0
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
Timepoint [22] 0 0
Up to Week 48
Secondary outcome [23] 0 0
The Percentage of Participants With Viral Breakthrough at Different Time Points
Timepoint [23] 0 0
Up to Week 48
Secondary outcome [24] 0 0
Time From End-of-treatment to Viral Relapse
Timepoint [24] 0 0
Up to Week 72
Secondary outcome [25] 0 0
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
Timepoint [25] 0 0
Up to Week 48
Secondary outcome [26] 0 0
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
Timepoint [26] 0 0
Up to Week 48
Secondary outcome [27] 0 0
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
Timepoint [27] 0 0
Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12
Secondary outcome [28] 0 0
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
Timepoint [28] 0 0
Before administration of TMC435 at Weeks 2, 4, 8, and 12
Secondary outcome [29] 0 0
Plasma Concentration of TMC435: Systemic Clearance (CL)
Timepoint [29] 0 0
Across Weeks 2, 4, 8, and 12
Secondary outcome [30] 0 0
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Timepoint [30] 0 0
Baseline to Week 60 and Week 72
Secondary outcome [31] 0 0
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Timepoint [31] 0 0
Baseline to Week 60 and Week 72
Secondary outcome [32] 0 0
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Timepoint [32] 0 0
Baseline to Week 60 and Week 72
Secondary outcome [33] 0 0
Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Timepoint [33] 0 0
Baseline to Week 60 and Week 72

Eligibility
Key inclusion criteria
* Genotype 1 hepatitis C infection (confirmed at screening)
* Patient has not received any prior treatment for hepatitis C
* Patient must have had a liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
* Must agree to use 2 forms of effective contraception throughout study (both males and females)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Infection with HIV or non genotype 1 hepatitis C
* Liver disease not related to hepatitic C infection
* Hepatic decompensation
* Significant laboratory abnormalities or other active diseases
* Pregnant or planning to become pregnant

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2013
Sample size
Target
Accrual to date
Final
395
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Darlinghurst
Recruitment hospital [2] 0 0
- Fitzroy
Recruitment hospital [3] 0 0
- Kingswood
Recruitment hospital [4] 0 0
- Melbourne
Recruitment hospital [5] 0 0
- Sydney
Recruitment hospital [6] 0 0
- Wolloongabba
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment postcode(s) [2] 0 0
- Fitzroy
Recruitment postcode(s) [3] 0 0
- Kingswood
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Sydney
Recruitment postcode(s) [6] 0 0
- Wolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
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
Pennsylvania
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
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Heidelberg
Country [20] 0 0
Germany
State/province [20] 0 0
Kiel
Country [21] 0 0
Germany
State/province [21] 0 0
Tübingen
Country [22] 0 0
Mexico
State/province [22] 0 0
Guadalajara
Country [23] 0 0
Mexico
State/province [23] 0 0
Mex Ctity
Country [24] 0 0
Mexico
State/province [24] 0 0
Monterrey
Country [25] 0 0
New Zealand
State/province [25] 0 0
Auckland
Country [26] 0 0
New Zealand
State/province [26] 0 0
Christchurch
Country [27] 0 0
New Zealand
State/province [27] 0 0
Hamilton
Country [28] 0 0
Puerto Rico
State/province [28] 0 0
San Juan
Country [29] 0 0
Romania
State/province [29] 0 0
Bucuresti
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Moscow
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Nizhny Novgorod
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Saint-Petersburg
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Samara
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Smolensk
Country [35] 0 0
Russian Federation
State/province [35] 0 0
St Petersburg
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Sevilla N/A
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia
Country [40] 0 0
Ukraine
State/province [40] 0 0
Donetsk
Country [41] 0 0
Ukraine
State/province [41] 0 0
Kiev
Country [42] 0 0
Ukraine
State/province [42] 0 0
Kyiv
Country [43] 0 0
Ukraine
State/province [43] 0 0
Vinnytsia
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Derby
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Liverpool
Country [46] 0 0
United Kingdom
State/province [46] 0 0
London
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Nottingham
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen R&D Ireland
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alpha-2a and ribavirin as part of their treatment.
Trial website
https://clinicaltrials.gov/study/NCT01289782
Trial related presentations / publications
Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.
Jacobson IM, Dore GJ, Foster GR, Fried MW, Radu M, Rafalsky VV, Moroz L, Craxi A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, De La Rosa G, Kalmeijer R, Scott J, Sinha R, Beumont-Mauviel M. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014 Aug 2;384(9941):403-13. doi: 10.1016/S0140-6736(14)60494-3. Epub 2014 Jun 4. Erratum In: Lancet. 2016 Apr 30;387(10030):1816. doi: 10.1016/S0140-6736(16)30322-1.
Public notes

Contacts
Principal investigator
Name 0 0
Janssen R&D Ireland Clinical Trial
Address 0 0
Janssen R&D Ireland
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/NCT01289782