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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01281839




Registration number
NCT01281839
Ethics application status
Date submitted
7/01/2011
Date registered
24/01/2011
Date last updated
23/04/2014

Titles & IDs
Public title
An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy
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 Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
Secondary ID [1] 0 0
TMC435HPC3007
Secondary ID [2] 0 0
CR017371
Universal Trial Number (UTN)
Trial acronym
PROMISE
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 - TMC435
Treatment: Drugs - Placebo
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 alfa-2a and ribavirin for 24 or 48 weeks

Placebo comparator: Placebo - Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks


Treatment: Drugs: TMC435
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks

Treatment: Drugs: Placebo
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 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
The 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 Week 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
The Percentage of Participants With Null Response
Timepoint [13] 0 0
Week 12
Secondary outcome [14] 0 0
The Percentage of Participants With Partial Response
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
The Percentage of Participants With Viral Breakthrough
Timepoint [15] 0 0
Up to Week 48
Secondary outcome [16] 0 0
The Percentage of Participants With Viral Relapse
Timepoint [16] 0 0
Up to Week 72
Secondary outcome [17] 0 0
The 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
The 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
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 or Detectable
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
From the time of administration up to 24 hours after dosing through Week 12
Secondary outcome [28] 0 0
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
Timepoint [28] 0 0
Before administration of TMC435 through Week 12
Secondary outcome [29] 0 0
Plasma Concentration of TMC435: Systemic Clearance (CL)
Timepoint [29] 0 0
From the time of administration through Week 12

Eligibility
Key inclusion criteria
* Genotype 1 hepatitis C infection (confirmed at screening)
* Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication
* 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
1/02/2013
Sample size
Target
Accrual to date
Final
394
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Kingswood
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Sydney
Recruitment hospital [5] 0 0
- Woolloongabba N/A
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Kingswood
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment postcode(s) [5] 0 0
- Woolloongabba N/A
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
Kentucky
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
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerpen
Country [12] 0 0
Belgium
State/province [12] 0 0
Brugge
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussel
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
France
State/province [20] 0 0
Creteil N/A
Country [21] 0 0
France
State/province [21] 0 0
Grenoble
Country [22] 0 0
France
State/province [22] 0 0
Lyon
Country [23] 0 0
France
State/province [23] 0 0
Nice N/A
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 12
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Rennes Cedex
Country [27] 0 0
France
State/province [27] 0 0
Vandoeuvre Les Nancy
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Düsseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Frankfurt
Country [31] 0 0
Germany
State/province [31] 0 0
Freiburg
Country [32] 0 0
Germany
State/province [32] 0 0
Halle (Saale)
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Kiel
Country [35] 0 0
Germany
State/province [35] 0 0
Leipzig
Country [36] 0 0
Germany
State/province [36] 0 0
Munchen
Country [37] 0 0
Germany
State/province [37] 0 0
Würzburg
Country [38] 0 0
New Zealand
State/province [38] 0 0
Auckland
Country [39] 0 0
New Zealand
State/province [39] 0 0
Christchurch
Country [40] 0 0
New Zealand
State/province [40] 0 0
Hamilton
Country [41] 0 0
Poland
State/province [41] 0 0
Bialystok
Country [42] 0 0
Poland
State/province [42] 0 0
Bydgoszcz
Country [43] 0 0
Poland
State/province [43] 0 0
Czeladz
Country [44] 0 0
Poland
State/province [44] 0 0
Kielce
Country [45] 0 0
Poland
State/province [45] 0 0
Krakow
Country [46] 0 0
Poland
State/province [46] 0 0
Warszawa
Country [47] 0 0
Puerto Rico
State/province [47] 0 0
Ponce Pr
Country [48] 0 0
Puerto Rico
State/province [48] 0 0
San Juan
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Moscow
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Saint-Petersburg
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Samara
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Smolensk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
St Petersburg
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Stavropol
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Madrid
Country [57] 0 0
Spain
State/province [57] 0 0
Sevilla N/A
Country [58] 0 0
Spain
State/province [58] 0 0
Valencia
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Birmingham
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Derby
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Glasgow
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London
Country [63] 0 0
United Kingdom
State/province [63] 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 patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.
Trial website
https://clinicaltrials.gov/study/NCT01281839
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.
Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, Brown A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, Scott J, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014 Jun;146(7):1669-79.e3. doi: 10.1053/j.gastro.2014.02.051. Epub 2014 Mar 3.
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/NCT01281839