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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03117569




Registration number
NCT03117569
Ethics application status
Date submitted
7/04/2017
Date registered
18/04/2017
Date last updated
4/06/2019

Titles & IDs
Public title
Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients
Scientific 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
Secondary ID [1] 0 0
VHCRP1701
Universal Trial Number (UTN)
Trial acronym
SMART-C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - glecaprevir (300mg)/pibrentasvir (120mg)

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).

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.


Treatment: Drugs: glecaprevir (300mg)/pibrentasvir (120mg)
glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Undetectable HCV RNA (ITT population) - Proportion of participants with undetectable HCV RNA based on ITT population.
Timepoint [1] 0 0
12 weeks post end of treatment (SVR12)
Secondary outcome [1] 0 0
Undetectable HCV RNA (mITT population) - Proportion of participants with undetectable HCV RNA based on mITT population.
Timepoint [1] 0 0
12 weeks post end of treatment (SVR12)
Secondary outcome [2] 0 0
Treatment and study visits adherence - Proportion adherent to treatment and study visits (on-treatment adherence and early treatment discontinuation).
Timepoint [2] 0 0
12 weeks post end of treatment (SVR12)
Secondary outcome [3] 0 0
Health-related quality of life - Change in health-related quality of life during treatment (measured by EQ-5D-3L).
Timepoint [3] 0 0
12 weeks post end of treatment (SVR12)
Secondary outcome [4] 0 0
HCV resistance - 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.
Timepoint [4] 0 0
12 weeks post end of treatment (SVR12)
Secondary outcome [5] 0 0
Patient treatment satisfaction - Patient treatment satisfaction measured by a questionnaire applied to all participants.
Timepoint [5] 0 0
12 weeks post end of treatment (SVR12)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
East Sydney Doctors - Sydney
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Sydney
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Sydney
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [6] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3065 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Wisconsin
Country [5] 0 0
Canada
State/province [5] 0 0
British Columbia
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
France
State/province [8] 0 0
Créteil
Country [9] 0 0
France
State/province [9] 0 0
Marseille
Country [10] 0 0
France
State/province [10] 0 0
Paris
Country [11] 0 0
Germany
State/province [11] 0 0
Berlin
Country [12] 0 0
Germany
State/province [12] 0 0
Düsseldorf
Country [13] 0 0
Germany
State/province [13] 0 0
Hanover
Country [14] 0 0
Germany
State/province [14] 0 0
Münster
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland
Country [16] 0 0
New Zealand
State/province [16] 0 0
Christchurch
Country [17] 0 0
New Zealand
State/province [17] 0 0
Dunedin
Country [18] 0 0
Switzerland
State/province [18] 0 0
Bern
Country [19] 0 0
Switzerland
State/province [19] 0 0
Zürich
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT03117569
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gregory Dore
Address 0 0
Kirby Institute, University of New South Wales Sydney, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications