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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01687257




Registration number
NCT01687257
Ethics application status
Date submitted
12/09/2012
Date registered
18/09/2012
Date last updated
16/09/2016

Titles & IDs
Public title
Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
Scientific title
A Phase 2, Multicenter, Open-Label, Randomized Study to Investigate the Safety and Efficacy of GS-7977 and Ribavirin Administered for 48 Weeks in Patients Infected With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
Secondary ID [1] 0 0
2012-002457-29
Secondary ID [2] 0 0
GS-US-334-0125
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Cirrhosis 0 0
Portal Hypertension 0 0
With or Without Liver Decompensation 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
Cardiovascular 0 0 0 0
Hypertension
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

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

Experimental: SOF+RBV - Participants will receive SOF+RBV for 48 weeks.

Experimental: Observation, then SOF+RBV - Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.


Treatment: Drugs: SOF
SOF 400 mg tablet administered orally once daily

Treatment: Drugs: RBV
RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and = 75 kg = 1200 mg)

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) - SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. For the Observation/SOF+RBV group, SVR12 during the observational period was defined as HCV RNA < LLOQ for 12 consecutive weeks, any time during the observational period.
Timepoint [1] 0 0
Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)
Secondary outcome [1] 0 0
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) - SVR4, SVR24, and SVR48 were defined as HCV RNA < LLOQ at 4, 24, and 48 weeks after stopping study treatment, respectively.
Timepoint [1] 0 0
Posttreatment Weeks 4, 24, and 48
Secondary outcome [2] 0 0
Percentage of Participants Experiencing On-Treatment Virologic Failure - On-treatment virologic failure was defined as:
Breakthrough (confirmed HCV RNA = LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
Non-response (HCV RNA persistently = LLOQ through 8 weeks of treatment)
Timepoint [2] 0 0
Up to 48 weeks
Secondary outcome [3] 0 0
Percentage of Participants Experiencing Viral Relapse - Viral relapse was defined as HCV RNA = LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.
Timepoint [3] 0 0
Up to Posttreatment Week 24
Secondary outcome [4] 0 0
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment - HVPG closely reflects the degree of portal hypertension in patients with cirrhosis. The end of treatment for the Observation group was defined as the end of the observation period. The treatment period for Group 2 was defined as the end of the observation period to the end of the treatment. Baseline values were the last available values on or prior to first dose date of any study drug.
Timepoint [4] 0 0
Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)
Secondary outcome [5] 0 0
Change From Baseline in Child-Pugh-Turcotte (CPT) Score - CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. Data are presented as improvement, no change, or worsening in CPT scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups).
Improvement in CPT score was defined as having a decrease in CPT score from baseline, no change in CPT score was defined as having no change in CPT score from baseline, and worsening in CPT score was defined as having an increase in CPT score from baseline.
Baseline values were the last available values on or prior to first dose date of any study drug.
Timepoint [5] 0 0
Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
Secondary outcome [6] 0 0
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores - MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. Data are presented as improvement, no change, or worsening in MELD scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups).
Improvement in MELD score was defined as having a baseline MELD score of 11-15 or 16-20 that changed to 0-10, or a baseline MELD score of 16-20 that changed to 11-15; no change in MELD score was defined as having no change in score group (0-10, 11-15, or 16-20) from baseline; and worsening in MELD score was defined as having a baseline MELD score of 0-10 that changed to 11-15 or 16-20, or a baseline MELD score of 11-15 that changed to 16-20.
Baseline values were the last available values on or prior to first dose date of any study drug.
Timepoint [6] 0 0
Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)

Eligibility
Key inclusion criteria
- Chronic infection with Hepatitis C with HCV RNA > 1000 IU/mL

- Individuals with cirrhosis with Child-Pugh score < 10

- Esophageal or gastric varices on endoscopy within 6 months prior to or at screening

- Hepatic Venous Pressure Gradient (HVPG) > 6 mmHg

- Body mass index (BMI) = 18 kg/m^2

- Naïve to all nucleotides/nucleoside treatments for chronic HCV infection
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have any serious or active medical or psychiatric illness which, in the opinion of the
investigator, would interfere with subject treatment, assessment, or compliance

- HIV or chronic hepatitis B virus (HBV) infection (HBsAg positive)

- Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the
last 6 months or during screening

- Refractory ascites as defined by requiring paracentesis > twice within 1 month prior
to screening

- Active variceal bleeding within 6 months of screening

- Expected survival of < 1 year

- History of hepatorenal, or hepatopulmonary syndrome.

- Evidence of renal impairment (CrCl < 50 mL/min)

- History of major organ transplantation, including liver transplant.

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 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
- Newtown
Recruitment postcode(s) [1] 0 0
- Newtown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
France
State/province [5] 0 0
Clichy
Country [6] 0 0
New Zealand
State/province [6] 0 0
Auckland
Country [7] 0 0
Spain
State/province [7] 0 0
Madrid
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the antiviral efficacy of combination therapy with sofosbuvir (SOF)
plus ribavirin (RBV) for 48 weeks in adults with compensated and decompensated chronic
hepatitis C virus (HCV) infection. Approximately 50 adults will be randomized (1:1) to
receive study drug for 48 weeks or take part in an untreated observational arm for the first
24 weeks followed by study drug for another 48 weeks.
Trial website
https://clinicaltrials.gov/show/NCT01687257
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shampa De-Oertel, PhD
Address 0 0
Gilead Sciences
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