Chronic Hepatitis C InfectionPhase 3MALACHITE 1NCT01854697
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
A Phase 3 study testing ABT-450/r/ABT-267, ABT-333, Ribavirin and Telaprevir in people with Chronic Hepatitis C Infection, run by AbbVie.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis C Infection
- What is being tested?
- ABT-450/r/ABT-267, ABT-333, Ribavirin and Telaprevir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 311 participants
- Where
- No sites listed yet
- Study dates
- Mar 2013to Jul 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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)
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.
Read the 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.
- Conditions
- Chronic Hepatitis C Infection
- Being tested
- ABT-450/r/ABT-267, ABT-333, Ribavirin, Telaprevir, Pegylated Interferon alpha 2-a (PegIFN)
- Keywords
- Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1
- Medical subject headings
- Hepatitis C, Chronic, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-450/r/ABT-267, ABT-333Drug
Also called Viekira Pak, ABT-267 also known as ombitasvir, ABT-450 also known as paritaprevir, ABT-333 also known as dasabuvir
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
RibavirinDrug
Tablet
TelaprevirDrug
Film-coated tablet
Pegylated Interferon alpha 2-a (PegIFN)Drug
Pre-filled syringe
| Study group | Role | What they receive |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Experimental | 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) Receives: Drug: ABT-450/r/ABT-267, ABT-333; Drug: Ribavirin |
| Arm B: TPV/PR in GT1a | Active comparator | 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) Receives: Drug: Ribavirin; Drug: Telaprevir; Drug: Pegylated Interferon alpha 2-a (PegIFN) |
| Arm C: 3-DAA + RBV in GT1b | Experimental | 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) Receives: Drug: ABT-450/r/ABT-267, ABT-333; Drug: Ribavirin |
| Arm D: 3-DAA in GT1b | Experimental | 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) Receives: Drug: ABT-450/r/ABT-267, ABT-333 |
| Arm E: TPV/PR in GT1b | Active comparator | 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) Receives: Drug: Ribavirin; Drug: Telaprevir; Drug: Pegylated Interferon alpha 2-a (PegIFN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks after the last actual dose of active study drug
Secondary outcomes (6)
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).
Measured: 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 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).
Measured: 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
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.
Measured: 12 weeks after the last actual dose of active 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.
Measured: 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E
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.
Measured: Within 24 weeks post 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.
Measured: 24 weeks after the last actual dose of active study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startMar 2013
- Primary completionNov 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis C InfectionStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 311 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yan Luo, MD, PhD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01854697
- Sponsor's protocol ID
- M13-774
- Other IDs
- 2012-003754-84
- Acronym
- MALACHITE 1
- Status last verified
- Jul 2016
- First submitted
- 8 Apr 2013
- Last updated
- 6 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 26321288
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01854697
- Acronym / sponsor ID
- MALACHITE 1 / M13-774
- Conditions
- Chronic Hepatitis C Infection
- Keywords
- Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 311 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Nov 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 15 May 2013 (estimated)
- Results
- Posted 22 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Experimental | Drug: ABT-450/r/ABT-267, ABT-333, Drug: RibavirinABT-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 B: TPV/PR in GT1a | Active comparator | Drug: Ribavirin, Drug: Telaprevir, Drug: Pegylated Interferon alpha 2-a (PegIFN)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 C: 3-DAA + RBV in GT1b | Experimental | Drug: ABT-450/r/ABT-267, ABT-333, Drug: RibavirinABT-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 D: 3-DAA in GT1b | Experimental | Drug: ABT-450/r/ABT-267, ABT-333ABT-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 E: TPV/PR in GT1b | Active comparator | Drug: Ribavirin, Drug: Telaprevir, Drug: Pegylated Interferon alpha 2-a (PegIFN)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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABT-450/r/ABT-267, ABT-333Also: Viekira Pak, ABT-267 also known as ombitasvir, ABT-450 also known as paritaprevir, ABT-333 also known as dasabuvirTablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet | Drug | Arm A: 3-DAA + RBV in GT1a, Arm C: 3-DAA + RBV in GT1b, Arm D: 3-DAA in GT1b |
| RibavirinTablet | Drug | Arm A: 3-DAA + RBV in GT1a, Arm B: TPV/PR in GT1a, Arm C: 3-DAA + RBV in GT1b, Arm E: TPV/PR in GT1b |
| TelaprevirFilm-coated tablet | Drug | Arm B: TPV/PR in GT1a, Arm E: TPV/PR in GT1b |
| Pegylated Interferon alpha 2-a (PegIFN)Pre-filled syringe | Drug | Arm B: TPV/PR in GT1a, Arm E: TPV/PR in GT1b |
Primary outcome
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.
6 secondary outcomes
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
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
Percentage of Participants With SVR12 - Secondary Efficacy Analyses
Time frame: 12 weeks after the last actual dose of active 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
Percentage of Participants With Post-treatment Relapse
Time frame: Within 24 weeks post 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26321288Dore 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yan Luo, MD, PhD study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ABT-450/r/ABT-267, ABT-333, Ribavirin and Telaprevir in people with Chronic Hepatitis C Infection, run by AbbVie.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01854697, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018.