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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02336139




Registration number
NCT02336139
Ethics application status
Date submitted
4/01/2015
Date registered
12/01/2015
Date last updated
27/02/2019

Titles & IDs
Public title
A Phase II Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use
Scientific title
A Phase II, Open-label, Single Arm, Multicentre, International Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use
Secondary ID [1] 0 0
VHCRP1309
Universal Trial Number (UTN)
Trial acronym
SIMPLIFY
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sofosbuvir (SOF)/GS-5816

Experimental: Sofosbuvir (SOF)/GS-5816 - 12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose combination


Treatment: Drugs: Sofosbuvir (SOF)/GS-5816
12 weeks of Sofosbuvir (SOF)/GS-5816 (400mg/100mg) in an oral once-daily fixed dose

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

Outcomes
Primary outcome [1] 0 0
Sustained Virological Response (SVR12) - To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir (SOF)/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use.
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Treatment adherence - To evaluate the proportion of patients adherent to therapy (both on-treatment adherence and treatment discontinuation)
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [2] 0 0
Impact of adherence on therapy (association between adherence and response to treatment ) - To evaluate the association between adherence and response to treatment [including an evaluation of the impact of early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) missed doses on response to therapy]; Adehernce will be measure via a self report quesitonanire and pill counts via return of the weeekly blister packs. The impact of the number and timing of missed pills will be evaluated.
Timepoint [2] 0 0
early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) during therapy
Secondary outcome [3] 0 0
Factors associated with on-treatment adherence - To evaluate factors associated with on-treatment adherence >90% and treatment discontinuation. Demographic and behavioural factors will be examined.
Timepoint [3] 0 0
Baseline to Week 12
Secondary outcome [4] 0 0
End of Treatment Response (ETR) (proportion of participants with undetectable HCV RNA at the end of treatment (ETR) - To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment (ETR)
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Safety and tolerability (number and type of adverse events and serious adverse events) - To evaluate the number and type of adverse events and serious adverse events on treament and for 12 weeks post end of treatment
Timepoint [5] 0 0
Baseline to Week 24
Secondary outcome [6] 0 0
Change in drug use - To evaluate the change in drug use during treatment
Timepoint [6] 0 0
Baseline to Week 12
Secondary outcome [7] 0 0
Change in mental health - To evaluate the change in mental health during treatment
Timepoint [7] 0 0
Basleine to Week 12
Secondary outcome [8] 0 0
Change in health related quality of life - To evaluate the change in health-related quality of life during treatment
Timepoint [8] 0 0
Baseline to Week 12
Secondary outcome [9] 0 0
Impact of mixed infection on treatment response - To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Reinfection Rate - To evaluate the rate of HCV reinfection during and up to two years following treatment
Timepoint [10] 0 0
Week 108
Secondary outcome [11] 0 0
Immunovirological factors associated with treatment clearance - To evaluate immunovirological factors associated with treatment clearance. We will evaluate cytokines and chemokines (e.g. interferon inducible protein 10), T-cell responses, viral evolution and genetic markers (e.g. inteferon lambda 4) that are potentially associated with treatment induced clearance
Timepoint [11] 0 0
Week 24
Secondary outcome [12] 0 0
Utility of Dried Blood Spot (DBS) (method for monitoring HCV including treatment response) - To evaluate the utility of dried blood spot (DBS) as a simple method for monitoring HCV including treatment response. HCV RNA will be measured from DBS samples and then compared to HCV RNA levels measured using standard methods (EDTA Plasma samples and Roche Taqman)
Timepoint [12] 0 0
Week 108

Eligibility
Key inclusion criteria
1. Participants 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 = 1000 IU/ml at Screening.

5. HCV genotypes 1-6.

6. Recent injecting drug use (previous 6 months).

7. Compensated liver disease.

8. Participants with Fibroscan >12 KPa or AFP >50 ng/mL must have an abdominal ultrasound
or CT scan without evidence of hepatocellular carcinoma within 2 months prior to
screening.

9. Negative pregnancy test at baseline (females of childbearing potential only).

10. All fertile males and 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. Malignancy within 5 years prior to screening, with exception of specific cancers
that may have been cured by surgical resection (basal cell skin cancer, etc.).
Subjects under evaluation for possible malignancy are also excluded.

5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).

2. Screening ECG with clinically significant abnormalities

3. Any of the following lab parameters at screening:

1. ALT > 10 x ULN

2. AST > 10 x ULN

3. Direct bilirubin > 1.5 x ULN

4. Platelets < 50,0000/µL

5. HbA1c > 8.5%

6. Creatinine clearance (CLcr) < 60 mL/min

7. Haemoglobin < 11 g/dL for females ; < 12 g/dL for males

8. Albumin < 30g/L

9. INR > 1.5 ULN unless subject has known haemophilia or is stable on an
anticoagulant regimen affecting INR

4. Pregnant or nursing female.

5. HIV infection or HBV infection (HBcAb and HBsAg positive)

6. Use of prohibited concomitant medications as described in section 5.2

7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone
equivalent > 10 mg/day)

8. Known hypersensitivity to GS-5816, sofosbuvir (SOF) or formulation excipients.

9. 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.

10. Any investigational drug =6 weeks prior to the first dose of study drug.

11. Previous therapy with sofosbuvir (SOF) or an NS5A inhibitor prior to the first dose of
study drug.

12. Ongoing severe psychiatric disease as judged by the treating physician.

13. Frequent injecting drug use that is judged by the treating physician to compromise
treatment safety.

14. 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
N/A
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 2
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
Recruitment hospital [1] 0 0
The Kirby Institute - Sydney
Recruitment postcode(s) [1] 0 0
2052 - Sydney

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

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of
treatment (SVR12) following sofosbuvir/GS-5816 therapy for 12 weeks in people with chronic
HCV infection and recent injection drug use.
Trial website
https://clinicaltrials.gov/show/NCT02336139
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Greg Dore, MBBS 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications