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

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ClinicalTrials.gov Identifier: NCT03117569
Recruitment Status : Active, not recruiting
First Posted : April 18, 2017
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
Kirby Institute

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: glecaprevir (300mg)/pibrentasvir (120mg) Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 21, 2017
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. Undetectable HCV RNA (ITT population) [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Proportion of participants with undetectable HCV RNA based on ITT population.


Secondary Outcome Measures :
  1. Undetectable HCV RNA (mITT population) [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Proportion of participants with undetectable HCV RNA based on mITT population.

  2. Treatment and study visits adherence [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Proportion adherent to treatment and study visits (on-treatment adherence and early treatment discontinuation).

  3. Health-related quality of life [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Change in health-related quality of life during treatment (measured by EQ-5D-3L).

  4. HCV resistance [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Sustained Virological Response (HCV RNA undetectable 12 weeks post-treatment) in participants with and without baseline Resistance Associated Substitutions (RAS) and RAS distribution in participants with virological failures.

  5. Patient treatment satisfaction [ Time Frame: 12 weeks post end of treatment (SVR12) ]
    Patient treatment satisfaction measured by a questionnaire applied to all participants.


Other Outcome Measures:
  1. 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%).

  2. 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.

  3. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03117569


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

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT03117569     History of Changes
Other Study ID Numbers: VHCRP1701
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: September 21, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis, Chronic