Hepatitis CPhase 2NCT01687257
Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
A Phase 2 study testing SOF and RBV in people with Hepatitis C and Cirrhosis, run by Gilead Sciences at 9 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Cirrhosis, Portal Hypertension
- What is being tested?
- SOF and RBV
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Jul 2012to Oct 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- History of hepatorenal, or hepatopulmonary syndrome.
- Evidence of renal impairment (CrCl < 50 mL/min)
- History of major organ transplantation, including liver transplant.
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
United States4 sites
Study site
Aurora, Colorado
Study site
Boston, Massachusetts
Study site
Philadelphia, Pennsylvania
Study site
Rochester, Minnesota
About this study
Official 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
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.
- Being tested
- SOF, RBV
- Medical subject headings
- Hepatitis C, Fibrosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SOFDrug
Also called Sovaldi®, GS-7977
SOF 400 mg tablet administered orally once daily
RBVDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| SOF+RBV | Experimental | Participants will receive SOF+RBV for 48 weeks. Receives: Drug: SOF; Drug: RBV |
| Observation, then SOF+RBV | Experimental | Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks. Receives: Drug: SOF; Drug: RBV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)
Secondary outcomes (6)
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.
Measured: Posttreatment Weeks 4, 24, and 48
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)
Measured: Up to 48 weeks
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.
Measured: Up to Posttreatment Week 24
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.
Measured: Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)
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.
Measured: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
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.
Measured: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2012 (estimated)
- Study startJul 2012
- Primary completionJan 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shampa De-Oertel, PhD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687257
- Sponsor's protocol ID
- GS-US-334-0125
- Other IDs
- 2012-002457-29
- Status last verified
- Aug 2016
- First submitted
- 12 Sep 2012
- Last updated
- 16 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01687257
- Acronym / sponsor ID
- GS-US-334-0125
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 18 Sep 2012 (estimated)
- Results
- Posted 24 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOF+RBV | Experimental | Drug: SOF, Drug: RBVParticipants will receive SOF+RBV for 48 weeks. |
| Observation, then SOF+RBV | Experimental | Drug: SOF, Drug: RBVParticipants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SOFAlso: Sovaldi®, GS-7977SOF 400 mg tablet administered orally once daily | Drug | Observation, then SOF+RBV, SOF+RBV |
| RBVRBV 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) | Drug | Observation, then SOF+RBV, SOF+RBV |
Primary outcome
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Time frame: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)
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.
6 secondary outcomes
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)
Time frame: Posttreatment Weeks 4, 24, and 48
Percentage of Participants Experiencing On-Treatment Virologic Failure
Time frame: Up to 48 weeks
Percentage of Participants Experiencing Viral Relapse
Time frame: Up to Posttreatment Week 24
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment
Time frame: Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)
Change From Baseline in Child-Pugh-Turcotte (CPT) Score
Time frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores
Time frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shampa De-Oertel, PhD study director
Gilead Sciences
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SOF and RBV in people with Hepatitis C and Cirrhosis, run by Gilead Sciences at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Spain, Australia, France, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (time frame: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2016.