Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients (SMART-C)

December 9, 2019 updated by: Kirby Institute

A Phase IIIb, Open-label, Multicentre, International Randomised Controlled Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir (300mg)/Pibrentasvir (120mg) in Chronic HCV Treatment naïve Patients Without Cirrhosis

The aim of this study is to determine if treatment monitoring schedule for chronic HCV patients treated with glecaprevir (300mg)/pibrentasvir (120mg) can be simplified.

Data has shown that direct acting antiviral (DAA) regimen of glecaprevir (300mg)/pibrentasvir (120mg), a protease inhibitor and NS5A inhibitor respectively , provides key features for HCV treatment simplification.

Eligible participants (naïve pre-cirrhosis chronic HCV patients) will be randomized (1:2) to the standard or simplified monitoring arm and will receive treatment for 8 weeks.

One post treatment visit will be conducted 12 weeks after the final dose of study medication to evaluate the proportion of patients with undetectable HCV RNA at this timepoint (SVR12).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The capacity to scale-up interferon-free DAA therapy would be enhanced by simplified treatment monitoring strategies. The "next generation" DAA regimen of glecaprevir (300mg)/pibrentasvir (120mg), a protease inhibitor and NS5A inhibitor, provides key features for HCV treatment simplification, including on-treatment monitoring: 1) pangenotypic activity with extremely high efficacy (SVR>95%); 2) no relationship between time to undetectable HCV RNA and SVR; 3) minimal drug-related toxicity; 4) ease of dosing (three pills once daily); and short duration (8 weeks in non-cirrhosis and 12 weeks in cirrhosis for treatment naïve patients). In phase II and III clinical trials in participants without cirrhosis, 8 weeks of glecaprevir (300mg)/pibrentasvir (120mg) has provided intention-to-treat SVR rates of 99.1%, 98%, 97%, and 93.1% in genotype 1, 2, 3, and 4-6 populations, respectively.

Current standard on-treatment monitoring in clinical trials involves clinic-based visits every 4 weeks. In the DAA era where treatments are highly tolerable, effective and short duration, this intensive monitoring strategy may no longer be required. A simplified on-treatment monitoring strategy is hypothesised to be non-inferior to the standard clinical trial on treatment monitoring strategy. If successful, a simplified on-treatment monitoring strategy is likely to be highly attractive to patients, clinicians and health care payers. It has the potential to improve the rapid scale up of treatment providing population level benefits in the reduction of global hepatitis C disease burden.

This study will be conducted as a Phase IIIb, randomised, controlled, multicentre, international trial.

There will be a maximum screening period of 6 weeks prior to Baseline. Eligible patients will be randomised into one of two on-treatment monitoring strategies; standard clinical trial monitoring (4-weekly on-treatment visits) vs simplified monitoring (no on-treatment visits). Randomisation will be 1:2 (standard vs simplified) and all participants will receive treatment with glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks.

All participants will attend the clinic for screening and baseline visit. Randomisation will occur at the baseline visit.

The two on-treatment monitoring strategies will differ as follows:

  • Standard monitoring arm participants will have on-treatment clinic visits at weeks 4 and 8 (EoT).
  • Simplified monitoring arm participants will have no on-treatment clinic visits.

Study nurse phone contact will also be made to participants in BOTH arms 1-2 days prior Week 4 and EoT (Week 8) visits to provide standardized reporting of adverse events, concomitant medication and adherence. One post treatment clinic visit will be conducted at SVR12 (week 20) for all participants.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
380

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2010
        • St Vincent's Hospital Sydney
      • Sydney, New South Wales, Australia, 2010
        • East Sydney Doctors
      • Sydney, New South Wales, Australia
        • Holdsworth House Medical Practice
    • South Australia
      • Adelaide, South Australia, Australia
        • Royal Adelaide Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Victoria, Australia, 3065
        • St Vincent's Hospital Melbourne
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 2K5
        • (G.I.R.I.) GI Research Institute
      • Vancouver, British Columbia, Canada, V5Z 1H2
        • Lair Centre
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health System
      • Hamilton, Ontario, Canada, L8N 4A6
        • St Joseph's Healthcare Hamilton
      • Toronto, Ontario, Canada, ON M57 2S8
        • Toronto General Hospital
    • Quebec
      • Montréal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre (MUHC)
      • Québec, Quebec, Canada, G1V 4G2
        • CHU de Quebec-Universite Laval
  • France
      • Créteil, France, 94000
        • Hôpital Henri Mondor
      • Marseille, France, 13008
        • Hopital Saint Joseph
      • Paris, France, 75012
        • Hôpital Saint Antoine
  • Germany
      • Berlin, Germany, 10439
        • zibp - Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
      • Düsseldorf, Germany, 40237
        • Center for HIV and Hepatogastroenterology
      • Hanover, Germany, 30625
        • Hannover Medical School
      • Münster, Germany, 48143
        • CIM-Centrum fuer Interdisziplinaere Medizin GmbH
  • New Zealand
      • Auckland, New Zealand, 1142
        • Auckland City Hospital
      • Auckland, New Zealand
        • Calder Center
      • Christchurch, New Zealand
        • Christchurch Hospital
      • Dunedin, New Zealand
        • Dunedin Hospital
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital - Universitaetsspital Bern
      • Zürich, Switzerland, 8091
        • University Hospital Zurich
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
      • London, United Kingdom, E1 1BB
        • Barts Health
      • London, United Kingdom, W2 1NY
        • Imperial College Healthcare NHS Trust (St Mary's Hospital)
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • New York
      • New York, New York, United States, 10016
        • New York University Langone Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • SSM Health Dean Medical Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Have voluntarily signed the informed consent form.
  2. 18 years of age or older.
  3. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months.
  4. HCV RNA plasma ≥ 10,000 IU/ml at screening.
  5. HCV genotype 1-6.
  6. HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV medication).
  7. Stage F0-3, based on: hepatic elastography <12.5 kPa on Fibroscan® or APRI <1.0.

  8. If co-infection with HIV is documented, the subject must meet the following criteria:

    • ART naïve with CD4 T cell count >500 cells/mm3; OR
    • On a stable ART regimen (containing only permissible ART - see protocol section 3.2) for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and a plasma HIV RNA level below the limit of detection.
  9. Negative pregnancy test at screening and baseline (females of childbearing potential only).
  10. All fertile females must be using effective contraception during treatment and during the 30 days after treatment end.

Exclusion Criteria:

  1. History of any of the following:

    1. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded.
    2. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage).
    3. Solid organ transplant.
    4. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs.

  2. Any of the following lab parameters at screening:

    1. ALT > 10 x ULN
    2. AST > 10 x ULN
    3. Direct bilirubin > ULN
    4. Platelets < 90,000/μL (cells/mm3) if Fibroscan® <12.5 kPa OR < 150,000/μL (cells/mm3) if Fibroscan® is unavailable and patient is included with APRI <1
    5. Creatinine clearance (CLcr) < 50 mL/min
    6. Haemoglobin < 12g/dL for males; <11g/dL for females
    7. Albumin < LLN
    8. INR > 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR
  3. Pregnant or breastfeeding female.
  4. HBV infection (HBsAg positive).
  5. Use of prohibited concomitant medications as described in protocol section 5.2.
  6. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day for >2 weeks).
  7. Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug.
  8. Any investigational drug ≤6 weeks prior to the first dose of study drug.
  9. Ongoing severe psychiatric disease as judged by the treating physician.
  10. Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, propoxyphene, or alcohol, with the exception of a positive result (including methadone) associated with documented short-term use or chronic stable use of a prescribed medication in that class.
  11. Injecting drug use within the previous six months.
  12. Inability or unwillingness to provide informed consent or abide by the requirements of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Standard monitoring schedule
Participants will have on-treatment clinic visits at weeks 4 and 8. Participants have also phone contact-based visits at weeks 4 and 8 (1-2 days prior to scheduled clinic visits).
Drug: glecaprevir (300mg)/pibrentasvir (120mg)
glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks
Other Names:
  • Mavyret
Experimental: Simplified monitoring schedule
Participants will have no on-treatment clinic visits at weeks 4 and 8. Participants have phone contact-based visits at weeks 4 and 8.
Drug: glecaprevir (300mg)/pibrentasvir (120mg)
glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks
Other Names:
  • Mavyret

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Undetectable HCV RNA (ITT Population)
Time Frame: 12 weeks post end of treatment (SVR12)
Number of participants with undetectable HCV RNA based on ITT population.
12 weeks post end of treatment (SVR12)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Undetectable HCV RNA (mITT Population)
Time Frame: 12 weeks post end of treatment (SVR12)
Number of participants with undetectable HCV RNA based on mITT population.
12 weeks post end of treatment (SVR12)
Treatment and Study Visits Adherence
Time Frame: 12 weeks post end of treatment (SVR12)
Number adherent to treatment and study visits (on-treatment adherence and early treatment discontinuation).
12 weeks post end of treatment (SVR12)
Health-related Quality of Life
Time Frame: Screening and 12 weeks post end of treatment (SVR12)
Change in health-related quality of life score pre and post-treatment (measured by EQ-5D-3L). The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' (value of 100) and 'Worst imaginable health state' (value of 0). The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement. Higher scores indicate better outcomes.
Screening and 12 weeks post end of treatment (SVR12)
Number of Virological Failure Participants With NS3 and NS5A Polymorphisms at Baseline and Post-treatment Week 12
Time Frame: Baseline and 12 weeks post-treatment

Distribution of baseline resistance associated substitutions (RAS) in participants with virological failures. Baseline polymorphisms were detected by Sanger sequencing at the following amino acid positions:

NS3: 36, 56, 80, 155, 156, 166, 168 NS5A: 24, 28, 30, 31, 58, 93
Baseline and 12 weeks post-treatment
Patient Treatment Satisfaction
Time Frame: 12 weeks post end of treatment (SVR12)
Patient was satisfied with their treatment follow-up plan.
12 weeks post end of treatment (SVR12)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Common Adverse Events (Safety Outcome)
Time Frame: 12 weeks post end of treatment (SVR12)
Proportion of patients with common adverse events (reported in greater than 5%).
12 weeks post end of treatment (SVR12)
Severe/Life Threatening Adverse Events (Safety Outcome)
Time Frame: 12 weeks post end of treatment (SVR12)
Proportion of patients with at least one severe or potentially life threatening (grade 3 or 4) adverse event.
12 weeks post end of treatment (SVR12)
Provider Acceptability of Simplified Monitoring Strategy (Exploratory Outcome)
Time Frame: 12 weeks post end of treatment (SVR12)
Provider acceptability of simplified monitoring strategy measured by study specific questionnaire completed by each site Principal Investigator and the primary Research Nurse.
12 weeks post end of treatment (SVR12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kirby Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gregory Dore, Kirby Institute, University of New South Wales Sydney, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 21, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 19, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 19, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VHCRP1701

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

No individual participant data will be shared. The results of the project will be presented at scientific meetings, and published in peer reviewed scientific literature. Sharing of data generated by this project is an essential part of our proposed activities and will be carried out in several different ways. We plan to make our results available to the community of scientists interested in recently acquired hepatitis C, community organisations representing the affected communities and participants. We also welcome collaboration with others who could make use of data and samples.

IPD Sharing Time Frame

Submitted as part of J Hepatology accepted publication

IPD Sharing Access Criteria

Access via the J Hepatology accepted publication

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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