Hepatitis CPhase 2NCT01559844
Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
A Phase 2 study testing Sofosbuvir and Ribavirin in people with Hepatitis C and Hepatocellular Carcinoma, run by Gilead Sciences at 15 sites in 3 countries.
Trial summary
The primary objective is to determine if the administration of a combination of sofosbuvir (SOF; GS-7977; PSI-7977) and ribavirin (RBV) to HCV-infected adults with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation could prevent post-transplant re-infection as… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Hepatocellular Carcinoma
- What is being tested?
- Sofosbuvir and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 15 sitesin 3 countries
- Study dates
- Mar 2012to Oct 2014
- 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
- Willing and able to provide written informed consent
- Males or females, age > 18 years old
- Males must agree to consistently and correctly use a condom while their female partner agrees to use an approved form of birth control from the date of screening until 7 months after their last dose of ribavirin.
- Confirmation of chronic HCV infection documented by at least one measurement of serum HCV RNA above the LLOQ measured at screening, and at least one of the following:
- Positive anti-HCV antibody test, HCV RNA or HCV genotyping test at least 6 months prior to the baseline/Day 1 visit together with positive HCV RNA test and anti-HCV antibody at the time of screening, or
- Positive HCV RNA test and anti-HCV antibody test at the time of screening together with either a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic HCV infection, such as the presence of fibrosis)
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- HCV RNA > 10^4 IU/mL at screening
- Patients meeting the MILAN criteria undergoing liver transplant for HCC secondary to HCV with a MELD of < 22 and a HCC weighted MELD of ≥ 22.
- Child-Pugh Score (CPT) ≤ 7
- Planned management of the subject to meet United Network for Organ Sharing (UNOS) criteria, with imaging studies made available for review if required.
- Has not been treated with any investigational drug or device within 30 days of the screening visit.
Who cannot join
- Females of child-bearing potential who is pregnant or nursing
- Prior exposure to a direct-acting antiviral targeting the HCV nonstructural (NS)5B polymerase
- Any transplant patient who has agreed to a liver transplant from a live donor.
- Participants requiring planned induction therapy with biologics posttransplantation or with a posttransplantation immunosuppressive regimen not consistent with the following within the first 12 weeks posttransplant:
- Solumedrol/Prednisone (tapering over approximately 7 days)
- Tacrolimus (maintaining a serum level of 5 12 ng/mL)
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- Mycophenolate mofetil (up to 2 g/day)
- Introduction of new maintenance immunosuppressants different from the above list is disallowed except in consultation during the first 12 weeks posttransplant
- Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated cirrhosis.
- Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis)
- Infection with hepatitis B virus (HBV) or HIV
- Contraindications to RBV therapy
- Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day) in the pretransplant treatment period.
- History of previous solid organ transplantation
- Evidence of renal impairment (CLcr < 60 mL/min) calculated by the Cockcroft-Gault equation.
- History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, porphyria, or poorly controlled diabetes, cancer other than HCC, or a history of malignancy that in the opinion of the investigator makes the patient unsuitable for the study. Patients with clinical signs or symptoms of acute pancreatitis with elevated lipase (at Screening or during the screening period)
- Known hypersensitivity to RBV, the study investigational medicinal product, the metabolites, or formulation excipients
- History of having received any systemic antineoplastic (including sorafenib) or immunomodulatory treatment (including radiation) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study (excluding a local regional therapy such as TACE).
- Treatment with Transcatheter arterial chemoembolization (TACE) or radio frequency ablation (RFA) within 30 days prior to the first dose.
- Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration at the baseline/Day 1 Visit.
Trial locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
United States13 sites
University of Colorado
Aurora, Colorado, 80010
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Lahey Clinic Medical Center
Burlington, Massachusetts, 01805
Baylor Health Care System
Dallas, Texas, 75246
Henry Ford Hospital
Detroit, Michigan, 48202
UCLA Medical Center-The Pfleger Liver Institute
Los Angeles, California, 90095
University of Miami
Miami, Florida, 33102-5405
Mount Sinai Medical Center
Miami Beach, Florida, 33140
Columbia University
New York, New York, 10032
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
UC San Diego
San Diego, California, 92103
University of California, San Francisco
San Francisco, California, 94143-0124
St. Louis University Hospital
St Louis, Missouri, 63110-0250
About this study
Official title: An Open-Label Study to Explore the Clinical Efficacy of GS-7977 With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
The primary objective is to determine if the administration of a combination of sofosbuvir (SOF; GS-7977; PSI-7977) and ribavirin (RBV) to HCV-infected adults with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation could prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.
Participants will enroll in the pretransplant treatment phase (24 or 48 weeks). Participants enrolling for 24 weeks in the pretransplant treatment phase may receive treatment for up to an additional 24 weeks in the pretransplant retreatment phase. Participants enrolling for 48 weeks in the pretransplant treatment will have a second baseline at Week 24 for combined analysis in the pretransplant retreatment phase.
Participants who undergo liver transplant will stop all study drug 24 hours prior to transplant, and enter a 48-week follow-up phase to monitor for recurrent HCV infection.
- Conditions
- Hepatitis C, Hepatocellular Carcinoma
- Being tested
- Sofosbuvir, Ribavirin
- Keywords
- Hepatitis, Chronic, hepatocellular carcinoma, HCC, transplant
- Medical subject headings
- Hepatitis C, Carcinoma, Hepatocellular, Hepatitis, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SofosbuvirDrug
Also called GS-7977, PSI-7977, Sovaldi®
Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily
RibavirinDrug
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
| Study group | Role | What they receive |
|---|---|---|
| SOF+RBV | Experimental | Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first. Receives: Drug: Sofosbuvir; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Measured: Posttransplant Week 12
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Measured: Up to 48 weeks prior to transplant
Percentage of Participants With Graft Loss Following Transplant
Measured: Up to 48 weeks following transplant
Number of Participants Who Died
- Treatment-emergent deaths were those that occurred while taking study drug or to the minimum of 1) date of transplantation, 2) retreatment 1st dose date, or 3) last dose date + 30 days.
- Only those participants who underwent liver transplantation were analyzed for death post-transplantation.
Measured: Up to 48 weeks following transplant
Secondary outcomes (4)
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at the relevant time point after transplant.
Measured: Up to 48 weeks following transplant
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Measured: Up to 48 weeks prior to transplant
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Measured: Up to 8 weeks prior to transplant
Proportion of Participants With Virologic Failure Prior to Transplant
Virologic failure (VF) in the pretransplant phase was defined by:
- Breakthrough (HCV RNA ≥ 25 IU/ml after having previously had HCV RNA < 25 IU/ml, while on treatment)
- Rebound (breakthrough or > 1 log10 IU/ml increase in HCV RNA from nadir while on treatment)
- Non-response (HCV RNA ≥ 25 IU/ml through 8 weeks of treatment)
- Pre-transplant relapse (HCV RNA ≥ 25 IU/ml during the Pre-Transplant off-treatment follow-up period after having achieved HCV RNA < 25 IU/ml at last observed HCV RNA on treatment)
Measured: Up to 48 weeks prior to transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionMay 2014
- Study completionOct 2014
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.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jill Denning, MA, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01559844
- Sponsor's protocol ID
- P7977-2025
- Status last verified
- Jun 2016
- First submitted
- 5 Mar 2012
- Last updated
- 27 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Babusis D, Curry MP, Kirby B, Park Y, Murakami E, Wang T, Mathias A, Afdhal N, McHutchison JG, Ray AS. Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02587-17. doi: 10.1128/AAC.02587-17. Print 2018 May.
PubMed 29439971Curry MP, Forns X, Chung RT, Terrault NA, Brown R Jr, Fenkel JM, Gordon F, O'Leary J, Kuo A, Schiano T, Everson G, Schiff E, Befeler A, Gane E, Saab S, McHutchison JG, Subramanian GM, Symonds WT, Denning J, McNair L, Arterburn S, Svarovskaia E, Moonka D, Afdhal N. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015 Jan;148(1):100-107.e1. doi: 10.1053/j.gastro.2014.09.023. Epub 2014 Sep 28.
PubMed 25261839
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Explore the Clinical Efficacy of GS-7977 With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
- ClinicalTrials.gov ID
- NCT01559844
- Acronym / sponsor ID
- P7977-2025
- Conditions
- Hepatitis C, Hepatocellular Carcinoma
- Keywords
- Hepatitis, Chronic, hepatocellular carcinoma, HCC, transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- May 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 21 Mar 2012 (estimated)
- Results
- Posted 28 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to determine if the administration of a combination of sofosbuvir (SOF; GS-7977; PSI-7977) and ribavirin (RBV) to HCV-infected adults with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation could prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.
Participants will enroll in the pretransplant treatment phase (24 or 48 weeks). Participants enrolling for 24 weeks in the pretransplant treatment phase may receive treatment for up to an additional 24 weeks in the pretransplant retreatment phase. Participants enrolling for 48 weeks in the pretransplant treatment will have a second baseline at Week 24 for combined analysis in the pretransplant retreatment phase.
Participants who undergo liver transplant will stop all study drug 24 hours prior to transplant, and enter a 48-week follow-up phase to monitor for recurrent HCV infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SOF+RBV | Experimental | Drug: Sofosbuvir, Drug: RibavirinSofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Willing and able to provide written informed consent
- Males or females, age > 18 years old
- Males must agree to consistently and correctly use a condom while their female partner agrees to use an approved form of birth control from the date of screening until 7 months after their last dose of ribavirin.
- Confirmation of chronic HCV infection documented by at least one measurement of serum HCV RNA above the LLOQ measured at screening, and at least one of the following:
- HCV RNA > 10^4 IU/mL at screening
Key exclusion criteria (20 listed)
- Females of child-bearing potential who is pregnant or nursing
- Prior exposure to a direct-acting antiviral targeting the HCV nonstructural (NS)5B polymerase
- Any transplant patient who has agreed to a liver transplant from a live donor.
- Participants requiring planned induction therapy with biologics posttransplantation or with a posttransplantation immunosuppressive regimen not consistent with the following within the first 12 weeks posttransplant:
- Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated cirrhosis.
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 |
|---|---|---|
| SofosbuvirAlso: GS-7977, PSI-7977, Sovaldi®Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily | Drug | SOF+RBV |
| RibavirinRibavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) | Drug | SOF+RBV |
Primary outcome
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Time frame: Posttransplant Week 12
pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Time frame: Up to 48 weeks prior to transplant
Percentage of Participants With Graft Loss Following Transplant
Time frame: Up to 48 weeks following transplant
Number of Participants Who Died
Time frame: Up to 48 weeks following transplant
* Treatment-emergent deaths were those that occurred while taking study drug or to the minimum of 1) date of transplantation, 2) retreatment 1st dose date, or 3) last dose date + 30 days. * Only those participants who underwent liver transplantation were analyzed for death post-transplantation.
4 secondary outcomes
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Time frame: Up to 48 weeks following transplant
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Time frame: Up to 48 weeks prior to transplant
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Time frame: Up to 8 weeks prior to transplant
Proportion of Participants With Virologic Failure Prior to Transplant
Time frame: Up to 48 weeks prior to transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29439971Babusis D, Curry MP, Kirby B, Park Y, Murakami E, Wang T, Mathias A, Afdhal N, McHutchison JG, Ray AS. Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02587-17. doi: 10.1128/AAC.02587-17. Print 2018 May.
- Derived from this study: PubMed 25261839Curry MP, Forns X, Chung RT, Terrault NA, Brown R Jr, Fenkel JM, Gordon F, O'Leary J, Kuo A, Schiano T, Everson G, Schiff E, Befeler A, Gane E, Saab S, McHutchison JG, Subramanian GM, Symonds WT, Denning J, McNair L, Arterburn S, Svarovskaia E, Moonka D, Afdhal N. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015 Jan;148(1):100-107.e1. doi: 10.1053/j.gastro.2014.09.023. Epub 2014 Sep 28.
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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.
Jill Denning, MA study director
Gilead Sciences
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sofosbuvir and Ribavirin in people with Hepatitis C and Hepatocellular Carcinoma, run by Gilead Sciences at 15 sites in 3 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 11 inclusion and 20 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 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, New Zealand, Spain. 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 28 May 2015). 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 Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 (time frame: Posttransplant Week 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01559844, which also lists 2 linked publications.
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 27 Jul 2016.