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Trial record 21 of 540 for:    IFNA2 AND RBV AND IFN alfa-2

A Study of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin in Participants With Chronic HCV Infection

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ClinicalTrials.gov Identifier: NCT01846832
Recruitment Status : Completed
First Posted : May 3, 2013
Last Update Posted : September 21, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Brief Summary:
The purpose of this study is to evaluate the efficacy, tolerability, and safety of 12-weeks of treatment with TMC435 plus pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) in previously untreated adult participants with genotype 1 or genotype 4 chronic Hepatitis C Virus (HCV) infection.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Infection Drug: TMC435 Drug: Pegylated interferon alfa-2a (PegIFNα-2a) Drug: Ribavirin (RBV) Phase 3

Detailed Description:
This is a multicenter, international study where all participants will receive triple therapy with the following 3 medications: TMC435 also referred to as simeprevir (formerly known as TMC435350) which is an investigational medication in development for the treatment of chronic hepatitis C virus (HCV) infection, pegylated interferon alfa-2a (PegIFNα-2a), and ribavirin (RBV). PegIFNα-2a and RBV are commercially available therapies for HCV infection. Participants will receive treatment with TMC435, PegIFNα-2a, and RBV for 12 weeks. If blood levels of HCV ribonucleic acid (RNA) monitored at Weeks 2, 4, and 8 are below 25 IU/mL, all treatment will be stopped at Week 12. If HCV RNA values are above 25 IU/mL at Weeks 2, 4, or 8, treatment with PegIFNα-2a and RBV will continue for an additional 12 weeks (up to Week 24) unless protocol-specified stopping criteria are met at Week 4 or 12, at which time all treatment will be discontinued. The study will be conducted in 3 phases: a screening phase of maximum 6 weeks, a treatment phase extending from Day 1 (baseline) up to 12 or 24 weeks depending on the response to treatment, and a posttreatment follow-up period of 24 weeks after the participant's last planned dose of study drug. The duration of the participation (excluding screening phase) for each participant will vary between 36 and 48 weeks, depending on the response to treatment. Blood samples for laboratory analysis will be obtained from participants at protocol-specified time points during the study and participant safety will be monitored throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 232 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection
Study Start Date : September 2013
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015


Arm Intervention/treatment
Experimental: TMC435 + PegIFNα-2a + RBV
TMC435 will be administered as triple therapy with pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV).
Drug: TMC435
150 mg taken orally (by mouth) as a capsule with food once daily for 12 weeks.

Drug: Pegylated interferon alfa-2a (PegIFNα-2a)
180 mcg administered according to the manufacturer's prescribing information as a 0.5 mL subcutaneous (under the skin) (SC) injection once a week in the morning or evening for up to 24 weeks.
Other Name: Pegasys

Drug: Ribavirin (RBV)
1000 mg or 1200 mg administered according to the manufacturer's prescribing information for up to 24 weeks. If the participant's baseline body weight is < 75 kg, the total daily dose of RBV will be 1000 mg, administered orally (by mouth) as 400 mg (2 tablets of 200 mg, intake with food) in the morning and 600 mg (3 tablets of 200 mg, intake with food) in the evening. If the baseline body weight is > or = 75 kg, the total daily dose will be 1200 mg, administered as 600 mg in the morning and evening (3 tablets of 200 mg per intake, with food).
Other Name: Copegus




Primary Outcome Measures :
  1. The proportion (percentage) of participants infected wtih genotype 1 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12) [ Time Frame: Week 24 ]
    Participants are considered to have reached SVR12 if at the actual end of treatment hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 25 IU/mL undetectable, AND at the time point of SVR12 (i.e., 12 weeks after the planned end of treatment [EOT]), HCV RNA levels < 25 IU/mL undetectable.


Secondary Outcome Measures :
  1. The proportion (percentage) of participants infected wtih genotype 4 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12) [ Time Frame: Week 24 ]
    See SVR12 defined above.

  2. The proportion (percentage) of participants who achieve rapid virologic response (RVR) [ Time Frame: Week 4 ]
    Rapid virologic response (RVR) defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < 25 IU/mL undetectable measured 4 weeks after start of treatment. RVR will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  3. The proportion (percentage) of participants who achieve virologic response at Week 2 (W2VR) [ Time Frame: Week 2 ]
    Virologic response at Week 2 (W2VR) defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < 25 IU/mL (detectable or undetectable) measured 2 weeks after start of treatment. W2VR will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  4. The proportion (percentage) of participants with sustained virologic response 24 weeks after planned end of treatment (SVR24) [ Time Frame: Week 48 ]
    Participants are considered to have reached SVR24 if at the actual end of treatment hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 25 IU/mL undetectable, AND at the time point of SVR24 (i.e., 24 weeks after the planned end of treatment [EOT]) HCV RNA levels < 25 IU/mL undetectable. SVR24 will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  5. The proportion (percentage) of participants with sustained virologic response 12 weeks after planned end of treatment (SVR12) [ Time Frame: Week 24 ]
    SVR12 (defined above) will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  6. The proportion (percentage) of participants with > or = 2 log decrease in hepatitis C virus (HCV) RNA at each time point [ Time Frame: Up to Week 48 ]
    To be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  7. The proportion (percentage) of participants with hepatitis C virus (HCV) RNA < 25 IU/mL undetectable at each time point [ Time Frame: Up to Week 48 ]
    To be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  8. The proportion (percentage) of participants with viral breakthrough [ Time Frame: Up to Week 48 ]
    Viral breakthrough is a confirmed increase of > 1 log10 IU/mL in hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached, or a confirmed HCV RNA level of > 100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (< 25 IU/mL detectable) or undetectable (< 25 IU/mL undetectable) while on study treatment. Viral breakthrough will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  9. The proportion (percentage) of participants with viral relapse [ Time Frame: Up to Week 48 ]
    Participants are considered to have a viral relapse if at actual end of treatment hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 25 IU/mL undetectable, AND during the follow-up period HCV RNA levels > or = 25 IU/mL. Viral relapse will be assessed for all participants per assigned total treatment duration and per HCV genotype (separately).

  10. Change from Baseline in the Hepatitis C Treatment Symptom & Impact Questionnaire (HCV SIQ) symptom and impact scores [ Time Frame: Day 1 and at each study visit up to Week 48 ]
    The HCV SIQ asks participants to rate 26 symptoms associated with HCV or its treatment and how symptoms impacted the participants' life during the prior week. This questionnaire provides a simple tool for monitoring symptoms during HCV treatment and follow-up. To be assessed in participants with genotype 1 or genotype 4 HCV infection for both genotypes combined (subanalyses for each genotype separately will also be done).

  11. Change from Baseline in The Fatigue Severity Scale (FSS) total score [ Time Frame: Day 1 and at each study visit up to Week 48 ]
    The FSS will be used to document fatigue severity and impact of fatigue on participants' daily lives. To be assessed in participants with genotype 1 or genotype 4 HCV infection for both genotypes combined (subanalyses for each genotype separately will also be done).

  12. Change from Baseline in The Center for Epidemiologic Studies Depression Scale (CES-D) score [ Time Frame: Day 1 and at each study visit up to Week 48 ]
    The CES-D is a brief assessment that asks participants to rate how often in the past week they experienced 20 symptoms associated with depressive illness, will be used to assess depressive symptom severity. To be assessed in participants with genotype 1 or genotype 4 HCV infection for both genotypes combined (subanalyses for each genotype separately will also be done).

  13. Change from Baseline in The Work Productivity and Activity Index (WPAI) for Hepatitis C missed work time, daily activity impairment, and productivity scores [ Time Frame: Day 1 and at each study visit up to Week 48 ]
    The (WPAI) will be used to measure the impact of HCV on time missed from work (absenteeism), reduced performance while at work (productivity impairment), and impairment in daily activities without regard to employment status. To be assessed in participants with genotype 1 or genotype 4 HCV infection for both genotypes combined (subanalyses for each genotype separately will also be done).

  14. Change from Baseline in The EuroQol 5 Dimension (EQ5D) Visual Analog Scale (VAS) valuation index, and Descriptive System scores [ Time Frame: Day 1 and at each study visit up to Week 48 ]
    The EQ-5D questionnaire is an instrument designed to assess overall health status using 5 health dimension scores (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and a "thermometer" visual analog scale (VAS) ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). To be assessed in participants with genotype 1 or genotype 4 HCV infection for both genotypes combined (subanalyses for each genotype separately will also be done).

  15. The proportion (percentage) of participants with normalized alanine aminotransferase (ALT) levels [ Time Frame: Up to Week 48 ]
    To be assessed in participants with genotype 1 or genotype 4 HCV infection (separately by genotype)

  16. Change from Screening in liver disease stage assessment [ Time Frame: Week -6; Week 48 ]
    To be assessed in participants with genotype 1 or genotype 4 HCV infection (separately by genotype).

  17. The number of participants reporting adverse events as a measure of safety and tolerability [ Time Frame: Up to Week 48 ]
    All participants will be monitored throughout the study for the occurrence of adverse events including psychiatric symptoms, anemia, hyperglycemia (elevated glucose levels), disturbances in serum creatinine levels (a measure of renal [kidney] safety), decreased White Blood Cell (WBC) Count, decreased Platelet Count (ability of the blood to clot), and thyroid abnormalities.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • treatment-naïve with confirmed chronic Hepatitis C Virus (HCV) infection
  • liver biopsy performed within 2 years prior to screening or non-invasive confirmation of the liver disease stage (by transient elastography) performed within 6 months prior to screening
  • liver disease stage equivalent to Metavir Score F0-F2 (no fibrosis, or portal fibrosis without or with few septa)

Exclusion Criteria:

-Participants with advanced liver disease equivalent to Metavir score F3-F4 (bridging fibrosis or cirrhosis), with hepatic decompensation, with any liver disease of non-HCV etiology, and/or with a non-genotype 1 or non-genotype 4 hepatitis C, hepatitis B or HIV co-infection will be excluded from the study


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01846832


Locations
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Austria
Linz, Austria
Wien, Austria
Belgium
Brussels, Belgium
Brussel, Belgium
Edegem, Belgium
France
Clichy, France
Limoges Cedex, France
Orleans, France
St Laurent Du Var, France
Germany
Berlin, Germany
Düsseldorf, Germany
Frankfurt, Germany
Hamburg, Germany
Würzburg, Germany
Saudi Arabia
Riyadh, Saudi Arabia
Spain
Barcelona, Spain
Madrid, Spain
Valencia, Spain
Valme, Spain
United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
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Study Director: JJanssen-Cilag International NV Clinical Trial Janssen-Cilag International NV

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01846832     History of Changes
Other Study ID Numbers: CR100981
TMC435HPC3014 ( Other Identifier: Janssen-Cilag International NV )
2012-004905-29 ( EudraCT Number )
First Posted: May 3, 2013    Key Record Dates
Last Update Posted: September 21, 2016
Last Verified: September 2016
Keywords provided by Janssen-Cilag International NV:
Hepatitis C, Chronic
Infection
Triple therapy
TMC435
simeprevir
Pegylated interferon alfa-2a (PegIFNα-2a)
ribavirin (RBV)
PEGASYS
COPEGUS
Additional relevant MeSH terms:
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Interferons
Ribavirin
Interferon-alpha
Interferon alpha-2
Peginterferon alfa-2a
Infection
Communicable Diseases
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Simeprevir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Protease Inhibitors
Enzyme Inhibitors