Hepatitis C Virus Infection
Conditions
Keywords
renal transplant
Brief summary
This study will evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) for 12 or 24 weeks in adults with chronic genotype 1 or genotype 4 hepatitis C virus (HCV) infection who have had a kidney transplant.
Interventions
DRUGLDV/SOF
90/400 mg FDC tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Genotype 1 or 4 chronic HCV infection * Have received a kidney transplant more than 6 months before the Baseline visit * Cirrhosis determination * Screening laboratory parameters within defined thresholds * Use of two effective contraception methods if female of childbearing potential or sexually active male Key
Exclusion criteria
* Pregnant or nursing female or male with pregnant female partner * Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain -resolved skin cancers) * History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol * Planned or anticipated second kidney transplant 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 Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 24 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 24 | Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit. |
Countries
Austria, France, Germany, Italy
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe. The first participant was screened on 14 October 2014. The last study visit occurred on 16 June 2016.
Pre-assignment details
130 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF 12 Weeks LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant | 57 |
| LDV/SOF 24 Weeks LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant | 57 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | LDV/SOF 12 Weeks | LDV/SOF 24 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 8.3 | 53 years STANDARD_DEVIATION 10 | 53 years STANDARD_DEVIATION 9.2 |
| Cirrhosis Status No | 49 Participants | 48 Participants | 97 Participants |
| Cirrhosis Status Yes | 8 Participants | 9 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 53 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV genotype Genotype 1 | 51 Participants | 53 Participants | 104 Participants |
| HCV genotype Genotype 4 | 6 Participants | 4 Participants | 10 Participants |
| HCV RNA | 6.3 log10 IU/mL STANDARD_DEVIATION 0.63 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.53 | 6.3 log10 IU/mL STANDARD_DEVIATION 0.58 |
| HCV RNA Category < 800,000 IU/mL | 11 Participants | 16 Participants | 27 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 46 Participants | 41 Participants | 87 Participants |
| IL28b Status CC | 14 Participants | 18 Participants | 32 Participants |
| IL28b Status CT | 34 Participants | 34 Participants | 68 Participants |
| IL28b Status TT | 9 Participants | 5 Participants | 14 Participants |
| Prior HCV Treatment Status Treatment-Experienced | 17 Participants | 18 Participants | 35 Participants |
| Prior HCV Treatment Status Treatment-Naive | 40 Participants | 39 Participants | 79 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 54 Participants | 53 Participants | 107 Participants |
| Region of Enrollment Austria | 9 participants | 15 participants | 24 participants |
| Region of Enrollment France | 15 participants | 21 participants | 36 participants |
| Region of Enrollment Germany | 1 participants | 4 participants | 5 participants |
| Region of Enrollment Italy | 32 participants | 17 participants | 49 participants |
| Sex: Female, Male Female | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Male | 33 Participants | 33 Participants | 66 Participants |
| Years From Most Recent Kidney Transplant | 12.1 years STANDARD_DEVIATION 9.51 | 14.4 years STANDARD_DEVIATION 9.66 | 13.2 years STANDARD_DEVIATION 9.61 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 23 / 57 | 36 / 57 |
| serious Total, serious adverse events | 5 / 57 | 8 / 57 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 24 weeks
Population: Safety Analysis Set: participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 1.8 percentage of participants |
| LDV/SOF 24 Weeks | Percentage of Participants Who Permanently Discontinued Any 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 randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
| LDV/SOF 24 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
| LDV/SOF 24 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 100.0 percentage of participants |
| LDV/SOF 24 Weeks | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
Time frame: Up to Posttreatment Week 24
Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants With Virologic Failure | 0 percentage of participants |
| LDV/SOF 24 Weeks | Percentage of Participants With Virologic Failure | 0 percentage of participants |