Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting
Primary Purpose
Hepatitis C Virus Infection
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LDV/SOF
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Virus Infection focused on measuring liver transplant, hepatitis C, Gilead, Communicable Diseases, Infection, Liver Diseases, RNA Virus Infections
Eligibility Criteria
Key Inclusion Criteria:
- Willing and able to provide written informed consent or for those individuals where hepatic encephalopathy affects their ability to provide initial or ongoing consent, has an appropriate and legally-authorized representative (LAR) willing and able to provide consent on behalf of the individual.
- HCV RNA infection with quantifiable virus at screening
- Must have chronic genotype 1 or 4 HCV infection for ≥ 6 months by medical history or liver biopsy
- Currently on the liver transplantation wait list
- Screening electrocardiogram (ECG) without clinically significant abnormalities.
- A negative serum pregnancy test result is required for females
Key Exclusion Criteria:
- Any previous solid organ transplant
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with participant's treatment, assessment, or compliance
- HIV infection or a positive hepatitis B virus surface antigen result
- History of malignancy (with exception of hepatocellular carcinoma within Milan criteria, certain resolved skin cancers or other early cancer for which surgical resection is considered to be completely curative)
- Treatment with any approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
- Prior exposure to an HCV non-structural protein (NS)5A inhibitor
- Patients on hemodialysis prior to or at the time of transplantation will be excluded
- Creatinine clearance (CLcr) < 40 mL/min at screening or < 40 mL/min on day of transplant
- Participation in a clinical study with an investigational drug or biologic within 28 days prior to screening visit
- Receipt or planned receipt of an organ from an HCV positive donor
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LDV/SOF
Arm Description
Participants with genotype 1 or 4 HCV who are undergoing liver transplant will receive one dose of LDV/SOF prior to the transplant and then will receive LDV/SOF once daily for 4 weeks following the transplant.
Outcomes
Primary Outcome Measures
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, 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event
Secondary Outcome Measures
Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Percentage of Participants With Virologic Failure
Virologic failure was defined as:
End of treatment virologic failure:
Completed 28 days LDV/SOF treatment and had HCV RNA ≥ LLOQ at last measurement on treatment
Virologic relapse:
Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment HCV RNA measurement.
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02350569
Brief Title
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting
Official Title
A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic HCV for Use in the Peri-Operative Liver Transplantation Setting
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
May 22, 2015 (Actual)
Primary Completion Date
March 28, 2016 (Actual)
Study Completion Date
April 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the antiviral efficacy of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) therapy at the time of liver transplantation and through 4 weeks posttransplant in adults with genotype 1 or 4 hepatitis C virus (HCV) infection who are undergoing primary liver transplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Infection
Keywords
liver transplant, hepatitis C, Gilead, Communicable Diseases, Infection, Liver Diseases, RNA Virus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LDV/SOF
Arm Type
Experimental
Arm Description
Participants with genotype 1 or 4 HCV who are undergoing liver transplant will receive one dose of LDV/SOF prior to the transplant and then will receive LDV/SOF once daily for 4 weeks following the transplant.
Intervention Type
Drug
Intervention Name(s)
LDV/SOF
Other Intervention Name(s)
Harvoni®, GS-5885/GS-7977
Intervention Description
90/400 mg FDC tablet administered orally
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)
Description
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Time Frame
Posttreatment Week 4
Title
Percentage of Participants With Virologic Failure
Description
Virologic failure was defined as:
End of treatment virologic failure:
Completed 28 days LDV/SOF treatment and had HCV RNA ≥ LLOQ at last measurement on treatment
Virologic relapse:
Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment HCV RNA measurement.
Time Frame
Up to Posttreatment Week 12
Title
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28
Time Frame
Days 1, 3, 5, 7, 14, 21, and 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Willing and able to provide written informed consent or for those individuals where hepatic encephalopathy affects their ability to provide initial or ongoing consent, has an appropriate and legally-authorized representative (LAR) willing and able to provide consent on behalf of the individual.
HCV RNA infection with quantifiable virus at screening
Must have chronic genotype 1 or 4 HCV infection for ≥ 6 months by medical history or liver biopsy
Currently on the liver transplantation wait list
Screening electrocardiogram (ECG) without clinically significant abnormalities.
A negative serum pregnancy test result is required for females
Key Exclusion Criteria:
Any previous solid organ transplant
Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with participant's treatment, assessment, or compliance
HIV infection or a positive hepatitis B virus surface antigen result
History of malignancy (with exception of hepatocellular carcinoma within Milan criteria, certain resolved skin cancers or other early cancer for which surgical resection is considered to be completely curative)
Treatment with any approved or experimental medication with known anti-HCV activity within 1 month prior to screening date
Prior exposure to an HCV non-structural protein (NS)5A inhibitor
Patients on hemodialysis prior to or at the time of transplantation will be excluded
Creatinine clearance (CLcr) < 40 mL/min at screening or < 40 mL/min on day of transplant
Participation in a clinical study with an investigational drug or biologic within 28 days prior to screening visit
Receipt or planned receipt of an organ from an HCV positive donor
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
San Francisco
State/Province
California
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
New York
State/Province
New York
Country
United States
City
Dallas
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
PubMed Identifier
27959735
Citation
Levitsky J, Verna EC, O'Leary JG, Bzowej NH, Moonka DK, Hyland RH, Arterburn S, Dvory-Sobol H, Brainard DM, McHutchison JG, Terrault NA. Perioperative Ledipasvir-Sofosbuvir for HCV in Liver-Transplant Recipients. N Engl J Med. 2016 Nov 24;375(21):2106-2108. doi: 10.1056/NEJMc1611829. No abstract available.
Results Reference
result
Learn more about this trial
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting
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