Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01559844
• Date of registration: 05/03/2012
• Prospective Registration: No
• Primary sponsor: Gilead Sciences
• 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
• Date of first enrolment: March 2012
• Target sample size: 61
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01559844
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

New Zealand, Spain, United States

Contacts

• Name: Jill Denning, MA
• Affiliation: Gilead Sciences

Key inclusion & exclusion criteria

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.

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hepatitis C

Hepatocellular Carcinoma

Intervention(s)

Drug: Ribavirin

Drug: Sofosbuvir

Primary Outcome(s)

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]

Number of Participants Who Died [Time Frame: Up to 48 weeks following transplant]

Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 [Time Frame: Posttransplant Week 12]

Percentage of Participants With Graft Loss Following Transplant [Time Frame: Up to 48 weeks following transplant]

Secondary Outcome(s)

HCV RNA and Change From Baseline in HCV RNA Through Week 8 [Time Frame: Up to 8 weeks prior to transplant]

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]

Proportion of Participants With Virologic Failure Prior to Transplant [Time Frame: Up to 48 weeks prior to transplant]

Secondary ID(s)

P7977-2025

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/05/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01559844