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A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) in People With Hepatitis C Virus Infection Who Have Not Had Treatment Before (MALACHITE 1)

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ClinicalTrials.gov Identifier: NCT01854697
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : February 22, 2016
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE April 8, 2013
First Posted Date  ICMJE May 15, 2013
Results First Submitted Date  ICMJE November 4, 2015
Results First Posted Date  ICMJE February 22, 2016
Last Update Posted Date June 6, 2018
Study Start Date  ICMJE March 2013
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses [ Time Frame: 12 weeks after the last actual dose of active study drug ]
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2013)
The percentage of all dosed subjects with sustained virologic response following the last actual dose of study drug. [ Time Frame: 12 weeks after the last actual dose of active study drug ]
Hepatitis C virus ribonucleic acid less than the lower limit of quantification
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2016)
  • Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) [ Time Frame: From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E ]
    SF-36V2 is a generic 36-item questionnaire measuring health-related quality of life (HRQoL) covering 2 summary measures: physical component summary (PCS) and MCS; it consists of 8 subscales. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have choices per item. Scoring is done for both MCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL).
  • Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) [ Time Frame: From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E ]
    SF-36V2 is a generic 36-item questionnaire measuring HRQoL covering 2 summary measures: PCS and MCS; it consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, bodily pain, and general health perception. Participants self-report on items in a subscale that have choices per item. Scoring is done for both PCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL).
  • Percentage of Participants With SVR12 - Secondary Efficacy Analyses [ Time Frame: 12 weeks after the last actual dose of active study drug ]
    The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug.
  • Percentage of Participants With Virologic Failure During Treatment [ Time Frame: 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E ]
    Participants in Arms A, C or D demonstrating any of the following were considered virologic failures and discontinued therapy:
    • Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of >1 log10 IU/mL above nadir) at any time point during treatment
    • Failure to achieve HCV RNA < LLOQ by Week 6 or
    • Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA < LLOQ during treatment after HCV RNA < LLOQ.
    Participants in Arms B and E followed virologic stopping criteria described in the TPV Summary of Product Characteristics; they were considered virologic failures and discontinued therapy as follows:
    • HCV RNA > 1000 IU/mL at Week 4 to Week 12, discontinue TPV and pegIFN and RBV
    • HCV RNA > 1000 IU/mL at Week 12, discontinue pegIFN and RBV
    • Confirmed HCV RNA > lower limit of detection (LLOD) at Week 24, discontinue pegIFN and RBV
    • Confirmed HCV RNA > LLOD at Week 36, discontinue pegIFN and RBV.
  • Percentage of Participants With Post-treatment Relapse [ Time Frame: Within 24 weeks post treatment ]
    Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 24 weeks post treatment among participants completing treatment and with HCV RNA less than the LLOQ at the end of treatment.
  • Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) [ Time Frame: 24 weeks after the last actual dose of active study drug ]
    The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 24 weeks after the last dose of study drug.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2013)
  • Change in general health-related quality of life using the Short-Form 36 Version 2 health status survey (SF-36V2) Mental Component Summary (MCS) [ Time Frame: From Day 1 of treatment up to 12 weeks for arms A,C and D and up to 24 or 48 weeks for arms B and E ]
    Mean change in the MCS from baseline to final treatment visit
  • Change in general health-related quality of life using the SF-36V2 Physical Component Summary (PCS) scores [ Time Frame: From Day 1 of study up to week 12 for arms A,C and D and week 24 or week 48 for arms B and E ]
    Mean change in the PCS from baseline to final treatment visit
  • Percentage of subjects with sustained virologic response 12 weeks post-treatment [ Time Frame: 12 weeks after the last actual dose of active study drug ]
    Hepatitis C virus ribonucleic acid less than the lower limit of quantification
  • Percentage of subjects with virologic failures during treatment [ Time Frame: 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E ]
    Subjects in Arms A, C and D demonstrating any of the following will be discontinued from therapy:
    • Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of >1 log10 IU/mL above nadir) at any time point during treatment
    • Failure to achieve HCV RNA < LLOQ by Week 6 or
    • Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA < LLOQ during treatment after HCV RNA < LLOQ.
    Subjects in Arms B and E will follow the virologic stopping criteria described in the telaprevir Summary of Product Characteristics (SmPC). Subjects in Arm B will discontinue therapy as follows:
    1. HCV RNA > 1000 IU/mL at Week 4 to Week 12, discontinue telaprevir and pegIFN and RBV
    2. HCV RNA > 1000 IU/mL at Week 12, discontinue pegIFN and RBV
    3. Confirmed HCV RNA > Lower Limit of Ditection (LLOD) at Week 24, discontinue pegIFN and RBV d.
    Confirmed HCV RNA > LLOD at Week 36, discontinue pegIFN and RBV
  • Percentage of subjects with post-treatment relapse [ Time Frame: Within 48 weeks post treatment ]
    Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 48 weeks post treatment among subjects completing treatment and with HCV RNA less than the LLOQ at the end of treatment
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) in People With Hepatitis C Virus Infection Who Have Not Had Treatment Before
Official Title  ICMJE A Randomized, Open-Label Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 and ABT-333 Co-administered With and Without Ribavirin Compared to Telaprevir Co-administered With Pegylated Interferon α-2a and Ribavirin in Treatment-Naïve Adults With Chronic Hepatitis C Genotype 1 Virus Infection (MALACHITE I)
Brief Summary This is a study to evaluate the efficacy and safety of three experimental drugs compared with telaprevir (a licensed product) in people with hepatitis C virus infection who have not had treatment before.
Detailed Description The primary purpose of this study is to demonstrate that treatment with ABT-450/ritonavir (r)/ABT-267 and ABT-333 administered with or without ribavirin (RBV) has non-inferior efficacy compared to treatment with telaprevir and pegylated interferon alpha-2a (pegIFN) and RBV and to compare the safety of these regimens in treatment-naive hepatitis C virus (HCV) genotype (GT) 1a- and 1b-infected adults.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C Infection
Intervention  ICMJE
  • Drug: ABT-450/r/ABT-267, ABT-333
    Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
    Other Names:
    • Viekira Pak
    • ABT-267 also known as ombitasvir
    • ABT-450 also known as paritaprevir
    • ABT-333 also known as dasabuvir
    • Holkira Pak
  • Drug: Ribavirin
    Tablet
  • Drug: Telaprevir
    Film-coated tablet
  • Drug: Pegylated Interferon alpha 2-a (PegIFN)
    Pre-filled syringe
Study Arms  ICMJE
  • Experimental: Arm A: 3-DAA + RBV in GT1a
    ABT-450/r/ABT-267 150 mg/100 mg/25 mg once daily (QD) and ABT-333 250 mg twice daily (BID) and weight-based RBV for 12 weeks (3 direct-acting antivirals [DAAs] with RBV in GT1a)
    Interventions:
    • Drug: ABT-450/r/ABT-267, ABT-333
    • Drug: Ribavirin
  • Active Comparator: Arm B: TPV/PR in GT1a
    Telaprevir (TPV) 750 mg every 8 hours (q8h) and pegIFN 180 µg/week and weight-based RBV (PR) for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1a)
    Interventions:
    • Drug: Ribavirin
    • Drug: Telaprevir
    • Drug: Pegylated Interferon alpha 2-a (PegIFN)
  • Experimental: Arm C: 3-DAA + RBV in GT1b
    ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID and weight-based RBV for 12 weeks (3 DAAs with RBV in GT1b)
    Interventions:
    • Drug: ABT-450/r/ABT-267, ABT-333
    • Drug: Ribavirin
  • Experimental: Arm D: 3-DAA in GT1b
    ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID for 12 weeks (3 DAAs without RBV in GT1b)
    Intervention: Drug: ABT-450/r/ABT-267, ABT-333
  • Active Comparator: Arm E: TPV/PR in GT1b
    Telaprevir 750 mg q8h and pegIFN 180 µg/week and weight-based RBV for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1b)
    Interventions:
    • Drug: Ribavirin
    • Drug: Telaprevir
    • Drug: Pegylated Interferon alpha 2-a (PegIFN)
Publications * Dore GJ, Conway B, Luo Y, Janczewska E, Knysz B, Liu Y, Streinu-Cercel A, Caruntu FA, Curescu M, Skoien R, Ghesquiere W, Mazur W, Soza A, Fuster F, Greenbloom S, Motoc A, Arama V, Shaw D, Tornai I, Sasadeusz J, Dalgard O, Sullivan D, Liu X, Kapoor M, Campbell A, Podsadecki T. Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials. J Hepatol. 2016 Jan;64(1):19-28. doi: 10.1016/j.jhep.2015.08.015. Epub 2015 Aug 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2015)
311
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2013)
314
Actual Study Completion Date  ICMJE July 2015
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or females between 18 and 65 years, inclusive, at time of Screening
  • Females must be post-menopausal for more than 2 years or surgically sterile or practicing abstinence/specific forms of birth control
  • Subject has never received antiviral treatment for hepatitis C infection
  • Chronic HCV Genotype-1 infection prior to study enrollment

Exclusion Criteria:

  • Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab)
  • Females who are pregnant or plan to become pregnant, or breastfeeding
  • Any current or past clinical evidence of cirrhosis
  • Screening laboratory analyses that showing abnormal laboratory results
  • Use of contraindicated medications within 2 weeks of dosing and subject with contraindication for telaprevir, pegIFN and RBV
  • Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol
  • Positive screen for drugs or alcohol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Canada,   Chile,   Finland,   Hungary,   Norway,   Poland,   Romania,   Slovakia
 
Administrative Information
NCT Number  ICMJE NCT01854697
Other Study ID Numbers  ICMJE M13-774
2012-003754-84 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yan Luo, MD, PhD AbbVie
PRS Account AbbVie
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP