Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients
SMART-C
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
1 other identifier
interventional
380
8 countries
33
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2017
Shorter than P25 for phase_3
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2017
CompletedFirst Posted
Study publicly available on registry
April 18, 2017
CompletedStudy Start
First participant enrolled
August 21, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 19, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 19, 2018
CompletedResults Posted
Study results publicly available
December 11, 2019
CompletedDecember 11, 2019
December 1, 2019
1.3 years
April 7, 2017
July 17, 2019
December 9, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Undetectable HCV RNA (ITT Population)
Number of participants with undetectable HCV RNA based on ITT population.
12 weeks post end of treatment (SVR12)
Secondary Outcomes (5)
Undetectable HCV RNA (mITT Population)
12 weeks post end of treatment (SVR12)
Treatment and Study Visits Adherence
12 weeks post end of treatment (SVR12)
Health-related Quality of Life
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
Baseline and 12 weeks post-treatment
Patient Treatment Satisfaction
12 weeks post end of treatment (SVR12)
Other Outcomes (3)
Common Adverse Events (Safety Outcome)
12 weeks post end of treatment (SVR12)
Severe/Life Threatening Adverse Events (Safety Outcome)
12 weeks post end of treatment (SVR12)
Provider Acceptability of Simplified Monitoring Strategy (Exploratory Outcome)
12 weeks post end of treatment (SVR12)
Study Arms (2)
Standard monitoring schedule
OTHERParticipants 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).
Simplified monitoring schedule
EXPERIMENTALParticipants will have no on-treatment clinic visits at weeks 4 and 8. Participants have phone contact-based visits at weeks 4 and 8.
Interventions
glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks
Eligibility Criteria
You may qualify if:
- Have voluntarily signed the informed consent form.
- years of age or older.
- Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months.
- HCV RNA plasma ≥ 10,000 IU/ml at screening.
- HCV genotype 1-6.
- HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV medication).
- Stage F0-3, based on: hepatic elastography \<12.5 kPa on Fibroscan® or APRI \<1.0.
- 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.
- Negative pregnancy test at screening and baseline (females of childbearing potential only).
- All fertile females must be using effective contraception during treatment and during the 30 days after treatment end.
You may not qualify if:
- History of any of the following:
- 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.
- Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage).
- Solid organ transplant.
- History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs.
- Any of the following lab parameters at screening:
- ALT \> 10 x ULN
- AST \> 10 x ULN
- Direct bilirubin \> ULN
- 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
- Creatinine clearance (CLcr) \< 50 mL/min
- Haemoglobin \< 12g/dL for males; \<11g/dL for females
- Albumin \< LLN
- INR \> 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR
- Pregnant or breastfeeding female.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kirby Institutelead
Study Sites (33)
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
SSM Health Dean Medical Group
Madison, Wisconsin, 53715, United States
East Sydney Doctors
Sydney, New South Wales, 2010, Australia
St Vincent's Hospital Sydney
Sydney, New South Wales, 2010, Australia
Holdsworth House Medical Practice
Sydney, New South Wales, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
St Vincent's Hospital Melbourne
Melbourne, Victoria, 3065, Australia
Lair Centre
Vancouver, British Columbia, V5Z 1H2, Canada
(G.I.R.I.) GI Research Institute
Vancouver, British Columbia, V6Z 2K5, Canada
William Osler Health System
Brampton, Ontario, L6R 3J7, Canada
St Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6, Canada
Toronto General Hospital
Toronto, Ontario, ON M57 2S8, Canada
McGill University Health Centre (MUHC)
Montreal, Quebec, H4A 3J1, Canada
CHU de Québec-Université Laval
Québec, Quebec, G1V 4G2, Canada
Hopital Henri Mondor
Créteil, 94000, France
Hopital Saint Joseph
Marseille, 13008, France
Hopital Saint Antoine
Paris, 75012, France
zibp - Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
Berlin, 10439, Germany
Center for HIV and Hepatogastroenterology
Düsseldorf, 40237, Germany
Hannover Medical School
Hanover, 30625, Germany
CIM-Centrum fuer Interdisziplinaere Medizin GmbH
Münster, 48143, Germany
Auckland City Hospital
Auckland, 1142, New Zealand
Calder Center
Auckland, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Dunedin Hospital
Dunedin, New Zealand
Inselspital - Universitaetsspital Bern
Bern, 3010, Switzerland
University Hospital Zurich
Zurich, 8091, Switzerland
Barts Health
London, E1 1BB, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
Imperial College Healthcare NHS Trust (St Mary's Hospital)
London, W2 1NY, United Kingdom
Related Publications (1)
Dore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, Mullhaupt B, Wedemeyer H, Lacombe K, Matthews GV, Schultz M, Klein M, Hezode C, Mercade GE, Kho D, Petoumenos K, Marks P, Tatsch F, Dos Santos AGP, Gane E; SMART-C Study Group. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020 Mar;72(3):431-440. doi: 10.1016/j.jhep.2019.10.010. Epub 2019 Oct 23.
PMID: 31655134DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trials Manager
- Organization
- Viral Hepatitis Clinical Research Program Kirby Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Gregory Dore
Kirby Institute, University of New South Wales Sydney, Australia
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 7, 2017
First Posted
April 18, 2017
Study Start
August 21, 2017
Primary Completion
December 19, 2018
Study Completion
December 19, 2018
Last Updated
December 11, 2019
Results First Posted
December 11, 2019
Record last verified: 2019-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Submitted as part of J Hepatology accepted publication
- Access Criteria
- Access via the J Hepatology accepted publication
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.