Phase 2
Completed N=39
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Source: ClinicalTrials.gov NCT02249182 ↗Enrolled (actual)
39
Serious AEs
0.4%
Results posted
Apr 2019
Primary outcomePrimary: For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF — 12682.5; 8210.3; 11688.9; 10202.4 h*ng/mL
Summary
The primary objective of the PK Lead-in Phase of the study is to evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.
The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The primary objective of the Treatment Phase is to evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.
During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow tablets.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF |
12682.5; 8210.3; 11688.9; 10202.4; 7288.3; 9316.3 | — |
| PRIMARY Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase |
0; 0; 0; 0; 2.9 | — |
| SECONDARY For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA |
-4.34; -4.29; -4.32; -4.71; -4.55; -4.87 | — |
| SECONDARY Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase |
0; 0; 5.9 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4) |
98.0; 98.9; 100.0; 100.0; 97.1 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12) |
98.0; 98.9; 100.0; 100.0; 97.1 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) |
98.0; 98.9; 100.0; 100.0; 97.1 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough |
0; 0; 0; 0; 0 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse |
0; 1.1; 0; 0; 0 | — |
| SECONDARY For the Treatment Phase, Change From Baseline in HCV RNA |
-4.34; -4.27; -4.30; -4.54; -4.25; -4.74 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment |
40.0; 30.3; 0; 100.0; 29.4; 75.0 | — |
| SECONDARY For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization |
72.3; 75.7; 0; 50.0; 63.0; 89.8 | — |
| SECONDARY For the Treatment Phase, Change From Baseline in Height |
0.1; 0.1; 0.3; 0.7; 0.2; 0.0 | — |
| SECONDARY For the Treatment Phase, Change From Baseline in Weight |
0.1; 0.3; -0.5; 0.3; 0.1; 0.3 | — |
| SECONDARY For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair |
35; 52; 10; 1; 1; 0 | — |
| SECONDARY For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development |
34; 52; 10; 1; 1; 0 | — |
| SECONDARY For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair |
52; 34; 21; 9; 2; 0 | — |
| SECONDARY For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development |
53; 31; 21; 8; 5; 0 | — |
| SECONDARY Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1 |
89.0; 100.0; 11.0; 0; 72.7; 98.8 | — |
| SECONDARY Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1 |
41.2; 17.6; 11.8; 29.4 | — |
Eligibility Criteria
Key Inclusion Criteria
- Consent of parent or legal guardian required
- Chronic HCV infection
- Screening laboratory values within defined thresholds
Key Exclusion Criteria
- History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol.
- Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
- Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
- Pregnant or nursing females
- Known hypersensitivity to study medication
- Use of any prohibited concomitant medications as within 28 days of the Day 1 visit
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02249182). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.