Chronic Hepatitis C InfectionPhase 2NCT01911845
An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine
A Phase 2 study testing ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV) in people with Chronic Hepatitis C Infection and Chronic Hepatitis C, run by AbbVie.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults taking… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C Infection, Chronic Hepatitis C
- What is being tested?
- ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- No sites listed yet
- Study dates
- Apr 2013to Sep 2014
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile.
- Chronic HCV infection prior to study enrollment.
- Screening laboratory result indicating HCV genotype 1-infection.
- Subject must be treatment naive or previous pegylated interferon/ribavirin treatment experienced.
- Subjects must be on a stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening.
Who cannot join
- Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening.
- Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir.
- Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
- Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.
About this study
Official title: An Open-label, Single-Arm, Phase 2 Study to Evaluate the Combination of ABT-450/r/ABT-267 and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Hepatitis C Virus (HCV) Infection Taking Methadone or Buprenorphine
The purpose of this study is to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults taking methadone or buprenorphine ± naloxone.
Read the detailed description
This study consisted of 2 periods: a 12-week treatment period and a 48-week post-treatment period (for all participants who received study drugs). All participants who received at least 1 dose of study drug were to be followed for 48 weeks post-treatment to monitor for safety, HCV RNA, the emergence and/or persistence of resistant viral variants, and assessment of patient-reported outcome (PRO) instruments.
- Conditions
- Chronic Hepatitis C Infection, Chronic Hepatitis C
- Being tested
- ABT-450/r/ABT-267, ABT-333, Ribavirin (RBV)
- Keywords
- HCV Genotype 1, Hepatitis Genotype 1, Interferon Free, methadone, HCV, Buprenorphine, Hepatitis C, Viekira Pak, paritaprevir, Viekira, ombitasvir, dasabuvir
- 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-267Drug
Also called ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir
Tablet; ABT-450 coformulated with ritonavir and ABT-267
ABT-333Drug
Also called dasabuvir
Tablet
Ribavirin (RBV)Drug
Tablet
| Study group | Role | What they receive |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, plus RBV | Experimental | ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks Receives: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV) |
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 Post-treatment
The percentage of participants with sustained virologic response (plasma hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantification [< LLOQ]) 12 weeks after the last dose of study drug.
Measured: 12 weeks after the last actual dose of study drug
Secondary outcomes (6)
Percentage of Participants With Virologic Failure During Treatment
Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment) or fail to suppress (HCV RNA ≥ LLOQ) persistently during treatment with at least 6 weeks [≥ 36 days] of treatment.
Measured: Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Percentage of Participants With Virologic Relapse Post-treatment
Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. Completion of treatment was defined as a study drug duration ≥ 77 days.
Measured: From the end of treatment through 12 weeks after the last actual dose of study drug
Area Under the Plasma Concentration-time Curve (AUC) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC24 in ng*hr/mL)] was estimated using noncompartmental analyses. For ABT-450, ritonavir, and ABT-267, the AUC from time 0 to the last measureable concentration (AUCt in ng*hr/mL) was calculated instead of AUC24 due to time deviations at 24 hours. The AUCt values are approximately equivalent to AUC24. For ABT-333, ABT-333 M1, and RBV, the AUC from time 0 to 12 hours (AUC12 in ng*hr/mL) after the morning dose was calculated using the 24-hour concentration as the 12-hour concentration as dosing was twice a day and a 12-hour sample was not collected in this study.
Measured: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
Measured: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Time to Maximum Plasma Concentration (Tmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
Measured: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Plasma Trough Concentration (Ctrough) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Minimum plasma concentration (C trough; measured in ng/mL) was directly determined from the concentration-time data.
Measured: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2013 (estimated)
- Study startApr 2013
- Primary completionDec 2013
- Study completionSep 2014
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dan Cohen, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01911845
- Sponsor's protocol ID
- M14-103
- Status last verified
- Aug 2015
- First submitted
- 13 May 2013
- Last updated
- 30 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lalezari J, Sullivan JG, Varunok P, Galen E, Kowdley KV, Rustgi V, Aguilar H, Felizarta F, McGovern B, King M, Polepally AR, Cohen DE. Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine. J Hepatol. 2015 Aug;63(2):364-9. doi: 10.1016/j.jhep.2015.03.029. Epub 2015 Apr 1.
PubMed 25839406
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-Arm, Phase 2 Study to Evaluate the Combination of ABT-450/r/ABT-267 and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Hepatitis C Virus (HCV) Infection Taking Methadone or Buprenorphine
- ClinicalTrials.gov ID
- NCT01911845
- Acronym / sponsor ID
- M14-103
- Conditions
- Chronic Hepatitis C Infection, Chronic Hepatitis C
- Keywords
- HCV Genotype 1, Hepatitis Genotype 1, Interferon Free, methadone, HCV, Buprenorphine, Hepatitis C, Viekira Pak
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 30 Jul 2013 (estimated)
- Results
- Posted 6 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults taking methadone or buprenorphine ± naloxone.
Detailed description
This study consisted of 2 periods: a 12-week treatment period and a 48-week post-treatment period (for all participants who received study drugs). All participants who received at least 1 dose of study drug were to be followed for 48 weeks post-treatment to monitor for safety, HCV RNA, the emergence and/or persistence of resistant viral variants, and assessment of patient-reported outcome (PRO) instruments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, plus RBV | Experimental | Drug: ABT-450/r/ABT-267, Drug: ABT-333, Drug: Ribavirin (RBV)ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile.
- Chronic HCV infection prior to study enrollment.
- Screening laboratory result indicating HCV genotype 1-infection.
- Subject must be treatment naive or previous pegylated interferon/ribavirin treatment experienced.
- Subjects must be on a stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening.
Key exclusion criteria (4 listed)
- Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening.
- Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir.
- Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
- Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.
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-267Also: ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvirTablet; ABT-450 coformulated with ritonavir and ABT-267 | Drug | ABT-450/r/ABT-267 and ABT-333, plus RBV |
| ABT-333Also: dasabuvirTablet | Drug | ABT-450/r/ABT-267 and ABT-333, plus RBV |
| Ribavirin (RBV)Tablet | Drug | ABT-450/r/ABT-267 and ABT-333, plus RBV |
Primary outcome
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment
Time frame: 12 weeks after the last actual dose of 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 quantification [< LLOQ]) 12 weeks after the last dose of study drug.
6 secondary outcomes
Percentage of Participants With Virologic Failure During Treatment
Time frame: Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Percentage of Participants With Virologic Relapse Post-treatment
Time frame: From the end of treatment through 12 weeks after the last actual dose of study drug
Area Under the Plasma Concentration-time Curve (AUC) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Maximum Plasma Concentration (Cmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Time to Maximum Plasma Concentration (Tmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Plasma Trough Concentration (Ctrough) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
Time frame: Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25839406Lalezari J, Sullivan JG, Varunok P, Galen E, Kowdley KV, Rustgi V, Aguilar H, Felizarta F, McGovern B, King M, Polepally AR, Cohen DE. Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine. J Hepatol. 2015 Aug;63(2):364-9. doi: 10.1016/j.jhep.2015.03.029. Epub 2015 Apr 1.
- Related InfoLink provided by the sponsor.
Related trials for Chronic Hepatitis C Infection
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
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.
Dan Cohen, MD study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV) in people with Chronic Hepatitis C Infection and Chronic Hepatitis C, 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 5 inclusion and 4 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 30 May 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 6 Jan 2015). 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 Post-treatment (time frame: 12 weeks after the last actual dose of 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 NCT01911845, 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 30 May 2018.