Hepatitis C
Conditions
Keywords
7977, 5885, GS-7977, GS-5885, SOF, LDV, Sofosbuvir, Ledipasvir, FDC
Brief summary
This study is to evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in adults with nosocomial genotype 1 hepatitis C virus (HCV) infection.
Interventions
DRUGLDV/SOF
Ledipasvir (LDV)/sofosbuvir (SOF) 90/400 mg FDC tablet administered orally once daily
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
* Body mass index (BMI) greater than or equal to 18 kg/m\^2. * HCV RNA greater than or equal to 1000 IU/mL at screening. * Documented acquisition of nosocomial genotype 1 HCV infection within 36 months from the screening visit. * Screening laboratory values within predefined thresholds. * Use of two effective contraception methods if female of childbearing potential or sexually active male. * Healthy according to medical history and physical examination with the exception of HCV diagnosis.
Exclusion criteria
* Unstable cardiac disease including subjects with active angina pectoris and/or hospitalization for a cardiac condition within 24 weeks prior to screening. * Prior exposure to an HCV NS5a inhibitor. * Pregnant or nursing female. * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). * History of solid organ transplantation. * Current or prior history of clinical hepatic decompensation. * History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol. * Known hypersensitivity to LDV, SOF, or formulation excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Permanently Discontinuing Study Drug Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively. |
| Percentage of Participants With HCV RNA < LLOQ on Treatment | Up to 12 weeks | — |
| HCV RNA Change From Baseline | Baseline; Weeks 1, 4, and 8 | — |
| Percentage of Participants Experiencing Virologic Failure | Baseline 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
United States
Participant flow
Recruitment details
Participants were enrolled at 1 study site in the United States. The first participant was screened on 29 July 2013. The last study visit occurred on 18 August 2014.
Pre-assignment details
8 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF 12 Weeks LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | LDV/SOF 12 Weeks |
|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 8.7 |
| HCV RNA | 5.9 log10 IU/mL STANDARD_DEVIATION 0.58 |
| HCV RNA Category < 800,000 IU/mL | 3 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 2 participants |
| IL28b Status CC | 1 participants |
| IL28b Status CT | 3 participants |
| IL28b Status TT | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 5 participants |
| Race/Ethnicity, Customized White | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Percentage of Participants Permanently Discontinuing Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants Permanently Discontinuing Study Drug Due to an Adverse Event | 0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants who were enrolled 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) at 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
Secondary
HCV RNA Change From Baseline
Time frame: Baseline; Weeks 1, 4, and 8
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF 12 Weeks | HCV RNA Change From Baseline | Change at Week 1 | -4.36 log10 IU/mL | Standard Deviation 0.463 |
| LDV/SOF 12 Weeks | HCV RNA Change From Baseline | Change at Week 4 | -4.56 log10 IU/mL | Standard Deviation 0.576 |
| LDV/SOF 12 Weeks | HCV RNA Change From Baseline | Change at Week 8 | -4.56 log10 IU/mL | Standard Deviation 0.576 |
Secondary
Percentage of Participants Experiencing 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: Baseline to posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants Experiencing Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ on Treatment
Time frame: Up to 12 weeks
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 1 | 60.0 percentage of participants |
| LDV/SOF 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 8 | 100.0 percentage of participants |
| LDV/SOF 12 Weeks | Percentage of Participants With HCV RNA < LLOQ on Treatment | Week 12 | 100.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR 24 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF 12 Weeks | Percentage of Participants With Sustained Virologic Response 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 Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 100.0 percentage of participants |