Hepatitis C Virus Infection
Conditions
Keywords
liver transplant, hepatitis C, Gilead, Communicable Diseases, Infection, Liver Diseases, RNA Virus Infections
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.
Interventions
DRUGLDV/SOF
90/400 mg FDC tablet administered orally
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | 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 | Up to 4 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment. |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 12 | 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 | Days 1, 3, 5, 7, 14, 21, and 28 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. The first participant was screened on 22 May 2015. The last study visit occurred on 22 April 2016.
Pre-assignment details
36 participants were screened. 17 unique participants were enrolled into the study (3 received the Day -1 dose and had their transplant cancelled; 2 of these patients were re-enrolled into the Main Study; the 3rd was rescreened but not transplanted).
Participants by arm
| Arm | Count |
|---|---|
| Main Study (LDV/SOF 4 Weeks) One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Main Study (LDV/SOF 4 Weeks) |
|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HCV Genotype Genotype 1a | 11 Participants |
| HCV Genotype Genotype 1b | 5 Participants |
| HCV RNA | 5.6 log10 IU/mL STANDARD_DEVIATION 0.75 |
| HCV RNA Category < 800,000 IU/mL | 10 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 6 Participants |
| IL28b Status CC | 5 Participants |
| IL28b Status CT | 9 Participants |
| IL28b Status TT | 2 Participants |
| Prior HCV Treatment No | 9 Participants |
| Prior HCV Treatment Yes | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 16 | 0 / 1 |
| other Total, other adverse events | 1 / 3 | 14 / 16 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 5 / 16 | 0 / 1 |
Outcome results
Primary
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 4 weeks
Population: Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event | 0 percentage of participants |
Primary
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.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 87.5 percentage of participants |
Secondary
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
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 21 | 100.0 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 1 | 0 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 3 | 12.5 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 5 | 18.8 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 7 | 33.3 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 14 | 93.3 percentage of participants |
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 | Day 28 | 100.0 percentage of participants |
Secondary
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.
Time frame: Posttreatment Week 4
Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) | 87.5 percentage of participants |
Secondary
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.
Time frame: Up to Posttreatment Week 12
Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study (LDV/SOF 4 Weeks) | Percentage of Participants With Virologic Failure | 6.3 percentage of participants |