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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01559844




Registration number
NCT01559844
Ethics application status
Date submitted
5/03/2012
Date registered
21/03/2012
Date last updated
27/07/2016

Titles & IDs
Public title
Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
Scientific 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
Secondary ID [1] 0 0
P7977-2025
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Hepatocellular Carcinoma 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

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

Experimental: SOF+RBV - Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.


Treatment: Drugs: Sofosbuvir
Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Timepoint [1] 0 0
Posttransplant Week 12
Primary outcome [2] 0 0
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Timepoint [2] 0 0
Up to 48 weeks prior to transplant
Primary outcome [3] 0 0
Percentage of Participants With Graft Loss Following Transplant
Timepoint [3] 0 0
Up to 48 weeks following transplant
Primary outcome [4] 0 0
Number of Participants Who Died
Timepoint [4] 0 0
Up to 48 weeks following transplant
Secondary outcome [1] 0 0
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Timepoint [1] 0 0
Up to 48 weeks following transplant
Secondary outcome [2] 0 0
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Timepoint [2] 0 0
Up to 48 weeks prior to transplant
Secondary outcome [3] 0 0
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Timepoint [3] 0 0
Up to 8 weeks prior to transplant
Secondary outcome [4] 0 0
Proportion of Participants With Virologic Failure Prior to Transplant
Timepoint [4] 0 0
Up to 48 weeks prior to transplant

Eligibility
Key inclusion criteria
1. Willing and able to provide written informed consent

2. Males or females, age > 18 years old

3. 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.

4. 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)

5. HCV RNA > 10^4 IU/mL at screening

6. 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.

7. Child-Pugh Score (CPT) = 7

8. Planned management of the subject to meet United Network for Organ Sharing (UNOS)
criteria, with imaging studies made available for review if required.

9. Has not been treated with any investigational drug or device within 30 days of the
screening visit.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Females of child-bearing potential who is pregnant or nursing

2. Prior exposure to a direct-acting antiviral targeting the HCV nonstructural (NS)5B
polymerase

3. Any transplant patient who has agreed to a liver transplant from a live donor.

4. 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)

- 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

5. Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy,
hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated
cirrhosis.

6. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease,
alpha-1 antitrypsin deficiency, cholangitis)

7. Infection with hepatitis B virus (HBV) or HIV

8. Contraindications to RBV therapy

9. Chronic use of systemically administered immunosuppressive agents (eg, prednisone
equivalent > 10 mg/day) in the pretransplant treatment period.

10. History of previous solid organ transplantation

11. Evidence of renal impairment (CLcr < 60 mL/min) calculated by the Cockcroft-Gault
equation.

12. 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)

13. Known hypersensitivity to RBV, the study investigational medicinal product, the
metabolites, or formulation excipients

14. 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).

15. Treatment with Transcatheter arterial chemoembolization (TACE) or radio frequency
ablation (RFA) within 30 days prior to the first dose.

16. 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.

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
1/03/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
61
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
Spain
State/province [11] 0 0
Pamplona

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

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01559844
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jill Denning, MA
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01559844