Hepatitis C Virus Infection
Conditions
Keywords
HCV genotype 1 or 4 (GT-1 or GT-4), Direct Acting Antiviral, Combination Therapy, Hepatitis C, Chronic, Liver Diseases, Virus Diseases
Brief summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) infection in pediatric participants who are undergoing cancer chemotherapy.
Interventions
DRUGLDV/SOF
Tablet(s) 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
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Aged 12 to \<18 years * Parent or legal guardian must provide written informed consent * Treatment naïve or experienced children with genotype 1 or 4 HCV infection, and are on a maintenance cancer chemotherapy regimen * Receiving a protocol-approved maintenance chemotherapy regimen for a hematological malignancy * Chronic HCV infection (≥ 6 months) documented by medical history or liver biopsy * Screening laboratory values within defined thresholds * No History of solid organ or bone marrow transplantation * No history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage) NOTE: Other protocol defined Inclusion/
Exclusion criteria
may apply.
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, 50 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event | First dose date up to Week 12 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24) | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment. |
| HCV RNA Change From Baseline/Day 1 | Baseline; Weeks 1, 4, 8, and 12 | — |
| Percentage of Participants With 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 |
| Percentage of Participants With HCV RNA < LLOQ While on Treatment | Weeks 1, 4, 8, and 12 | — |
| Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment. |
Countries
Egypt
Participant flow
Recruitment details
Participants were enrolled at one study site in Egypt. The first participant was screened on 28 August 2016. The last study visit occurred on 03 February 2019.
Pre-assignment details
24 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| LDV/SOF LDV/SOF 90/400 mg FDC orally once daily for 12 weeks | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | LDV/SOF |
|---|---|
| Age, Continuous | 14 years STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HCV RNA | 5.3 log10 IU/mL STANDARD_DEVIATION 1.65 |
| HCV RNA Category < 800,000 IU/mL | 12 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 7 Participants |
| IL28B CC | 6 Participants |
| IL28B CT | 12 Participants |
| IL28B TT | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 15 / 19 |
| serious Total, serious adverse events | 3 / 19 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Time frame: First dose date up to Week 12
Population: Safety Analysis Set included participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants Who Permanently 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, 50 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set included participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 100.0 percentage of participants |
Secondary
HCV RNA Change From Baseline/Day 1
Time frame: Baseline; Weeks 1, 4, 8, and 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LDV/SOF | HCV RNA Change From Baseline/Day 1 | Change at Week 8 | -3.36 log10 IU/mL | Standard Deviation 1.526 |
| LDV/SOF | HCV RNA Change From Baseline/Day 1 | Change at Week 1 | -3.34 log10 IU/mL | Standard Deviation 1.73 |
| LDV/SOF | HCV RNA Change From Baseline/Day 1 | Change at Week 4 | -3.62 log10 IU/mL | Standard Deviation 1.653 |
| LDV/SOF | HCV RNA Change From Baseline/Day 1 | Change at Week 12 | -3.62 log10 IU/mL | Standard Deviation 1.653 |
Secondary
Percentage of Participants With HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24)
SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Time frame: Posttreatment Week 24
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24) | 100.0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ at 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: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of Therapy (SVR4) | 100.0 percentage of participants |
Secondary
Percentage of Participants With HCV RNA < LLOQ While on Treatment
Time frame: Weeks 1, 4, 8, and 12
Population: Participants in the Full Analysis Set were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 1 | 89.5 percentage of participants |
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 4 | 100.0 percentage of participants |
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 8 | 94.7 percentage of participants |
| LDV/SOF | Percentage of Participants With HCV RNA < LLOQ While on Treatment | Week 12 | 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: Baseline to Posttreatment Week 24
Population: Participants in Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDV/SOF | Percentage of Participants With Virologic Failure | 0 percentage of participants |