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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03855917




Registration number
NCT03855917
Ethics application status
Date submitted
25/02/2019
Date registered
27/02/2019
Date last updated
8/08/2019

Titles & IDs
Public title
Strategic Treatment Reduction in Very Early Liver Disease With 4 Weeks Sofosbuvir Plus Glecepravir-pibrentasvir
Scientific title
A Phase IV Open-label Multicentre International Pilot Study of 4-week Treatment With Sofosbuvir (400 mg) Plus Glecaprevir/Pibrentasvir (300mg/120mg) in Chronic HCV Treatment naïve Patients With Early Liver Disease
Secondary ID [1] 0 0
VHCRP1901
Universal Trial Number (UTN)
Trial acronym
STRIVE-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 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
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sofosbuvir 400mg [Sovaldi]
Treatment: Drugs - Glecaprevir/pibrentasvir (300mg/120mg)

Experimental: Sof plus G/P - Four weeks of sofosbuvir (400mg) plus glecaprevir-pibrentasvir (300mg/120mg) will be administered, followed by immediate retreatment of virological relapse with glecepravir/pibrentasvir (300mg/120mg) for 12 weeks, in treatment-naïve participants with chronic HCV infection and early liver disease (F0-F2).


Treatment: Drugs: Sofosbuvir 400mg [Sovaldi]
Four weeks.

Treatment: Drugs: Glecaprevir/pibrentasvir (300mg/120mg)
Four weeks.

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

Outcomes
Primary outcome [1] 0 0
SVR12 - To evaluate the proportion achieving a sustained virological response at 12 weeks post treatment (SVR12) with sofosbuvir (400 mg) plus glecaprevir/pibrentasvir (300mg/120mg) for four weeks.
Timepoint [1] 0 0
16 weeks
Secondary outcome [1] 0 0
Virological relapse - To evaluate virological relapse following 4 weeks sofosbuvir (400 mg) plus glecaprevir/pibrentasvir (300mg/120mg) in HCV treatment-naïve chronic HCV patients with early liver disease (F0-2).
Timepoint [1] 0 0
16 weeks
Secondary outcome [2] 0 0
Relapse characteristics - In patients with virological relapse, to evaluate the time course of relapse and emergence of treatment-associated resistance substitutions.
Timepoint [2] 0 0
32 weeks
Secondary outcome [3] 0 0
Re-treatment SVR - To evaluate SVR following re-treatment of virological relapse with 12 weeks glecaprevir/pibrentasvir (300mg/120mg).
Timepoint [3] 0 0
32 weeks
Secondary outcome [4] 0 0
Adherence - To evaluate the proportion adherent to treatment and study visits.
Timepoint [4] 0 0
32 weeks
Secondary outcome [5] 0 0
Cost-effectiveness - To evaluate cost-effectiveness of a shortened duration with re-treatment of relapse strategy, against a standard duration (8-week, historical data).
Timepoint [5] 0 0
32 weeks

Eligibility
Key inclusion criteria
- Participants must meet all inclusion criteria to be eligible to participate in this
study:

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. Quantifiable HCV RNA at screening.

5. HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV
medication).

6. Liver fibrosis stage F0-F2, defined by at least one of the following:

1. Liver stiffness measurement <9.5 kPa by transient elastography (FibroScan®)

2. AST to platelet ratio index (APRI) <0.5

3. Liver biopsy

7. 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
6.3) 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.

8. Negative pregnancy test at screening and baseline (females of childbearing potential
only).

9. 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
- Participants who meet any of the exclusion criteria are not to be enrolled in this
study.

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 < 150,000/µL (cells/mm3)

5. Creatinine clearance (CLcr) < 50 mL/min

6. Albumin < LLN

7. INR > 1.5 ULN

3. Pregnant or breastfeeding female.

4. HBV infection (HBsAg positive).

5. Use of prohibited concomitant medications as described in protocol section 6.3.

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. 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
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
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Blacktown Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2148 - Sydney

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

Ethics approval
Ethics application status

Summary
Brief summary
This study aims to evaluate the efficacy, safety and feasibility of four weeks of sofosbuvir
plus glecaprevir-pibrentasvir, followed by immediate retreatment of virological relapse with
glecepravir-pibrentasvir for 12 weeks, in treatment-naïve participants with chronic HCV
infection and early liver disease (F0-F2).
Trial website
https://clinicaltrials.gov/show/NCT03855917
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marianne Martinello, MD, PhD
Address 0 0
Kirby Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Marianne Martinello, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
+61293850900
Fax 0 0
Email 0 0
mmartinello@kirby.unsw.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03855917