Back to resultsA 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)
Primary Purpose
Chronic Hepatitis C Infection
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ABT-450/r/ABT-267, ABT-333
Ribavirin
Telaprevir
Pegylated Interferon alpha 2-a (PegIFN)
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Active Comparator
Experimental
Experimental
Active Comparator
Arm Label
Arm A: 3-DAA + RBV in GT1a
Arm B: TPV/PR in GT1a
Arm C: 3-DAA + RBV in GT1b
Arm D: 3-DAA in GT1b
Arm E: TPV/PR in GT1b
Arm Description
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)
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)
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)
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)
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)
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses
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.
Secondary Outcome Measures
Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS)
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)
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
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
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
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)
The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 24 weeks after the last dose of study drug.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01854697
Brief Title
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
Acronym
MALACHITE 1
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Infection
Keywords
Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
311 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: 3-DAA + RBV in GT1a
Arm Type
Experimental
Arm Description
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)
Arm Title
Arm B: TPV/PR in GT1a
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Arm C: 3-DAA + RBV in GT1b
Arm Type
Experimental
Arm Description
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)
Arm Title
Arm D: 3-DAA in GT1b
Arm Type
Experimental
Arm Description
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)
Arm Title
Arm E: TPV/PR in GT1b
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
ABT-450/r/ABT-267, ABT-333
Other Intervention Name(s)
Viekira Pak, ABT-267 also known as ombitasvir, ABT-450 also known as paritaprevir, ABT-333 also known as dasabuvir, Holkira Pak
Intervention Description
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Telaprevir
Intervention Description
Film-coated tablet
Intervention Type
Drug
Intervention Name(s)
Pegylated Interferon alpha 2-a (PegIFN)
Intervention Description
Pre-filled syringe
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses
Description
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.
Time Frame
12 weeks after the last actual dose of active study drug
Secondary Outcome Measure Information:
Title
Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS)
Description
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).
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
Title
Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS)
Description
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).
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
Title
Percentage of Participants With SVR12 - Secondary Efficacy Analyses
Description
The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 12 weeks after the last dose of study drug.
Time Frame
12 weeks after the last actual dose of active study drug
Title
Percentage of Participants With Virologic Failure During Treatment
Description
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.
Time Frame
12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E
Title
Percentage of Participants With Post-treatment Relapse
Description
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.
Time Frame
Within 24 weeks post treatment
Title
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
Description
The percentage of participants with sustained virologic response (plasma HCV RNA level < LLOQ) 24 weeks after the last dose of study drug.
Time Frame
24 weeks after the last actual dose of active study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yan Luo, MD, PhD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
26321288
Citation
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.
Results Reference
result
Links:
URL
http://rxabbvie.com
Description
Related Info
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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
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