Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection

Gilead Sciences226 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

226

Conditions

Hepatitis C Virus Infection

Interventions

Eligibility

Sex: ALLMin age: 3 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (31)

Unnamed facility

Birmingham, Alabama, United States

Unnamed facility

Los Angeles, California, United States

Unnamed facility

San Francisco, California, United States

Unnamed facility

Aurora, Colorado, United States

Unnamed facility

Washington D.C., District of Columbia, United States

Unnamed facility

Atlanta, Georgia, United States

Unnamed facility

Indianapolis, Indiana, United States

Unnamed facility

Louisville, Kentucky, United States

Unnamed facility

Baltimore, Maryland, United States

Unnamed facility

Boston, Massachusetts, United States

...and 21 more locations

Outcomes

Primary Outcomes

For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase

Time frame: Up to 24 weeks

Secondary Outcomes

For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA

Time frame: Baseline; Weeks 1, 2, 4, 8, and 12

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase

Time frame: Up to Day 10

For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)

SVR4 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment.

Time frame: Posttreatment Week 4

For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA \< LLOQ at 12 weeks after stopping study treatment.

Time frame: Posttreatment Week 12

For the Treatment Phase, Percentage of Participants With SVR 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

For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough

Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment.

Time frame: Up to 24 weeks

For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse

Viral relapse was defined as having 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

For the Treatment Phase, Change From Baseline in HCV RNA

Time frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)

For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment

Time frame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)

For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization

ALT normalization was defined as ALT \> the upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit.

Time frame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4

For the Treatment Phase, Change From Baseline in Height

Time frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24

For the Treatment Phase, Change From Baseline in Weight

Time frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24

For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair

Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

Time frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development

Time frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair

Time frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development

Time frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24

Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1

Participants who were able/unable to swallow placebo tablets were assessed. Participants 12 to \< 18 years old were first asked to perform the swallowability assessment using the 90/400 mg placebo tablet. If they were unable to swallow this, they were then asked to perform the swallowability assessment with 22.5/100 mg placebo tablets. Participants 6 to \< 12 years old were to be assessed with the 22.5/100 mg placebo tablets. However, 8 participants were mistakenly assessed using the 90/400 mg placebo tablet.

Time frame: Day 1

Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1

Participants who were dosed with granules were asked if they tasted the study drug. If they tasted it, then they were asked to provide a number from 0 to 100 to rate the taste of the study drug, with higher scores indicating better taste. Data was then summarized as percentage of participants choosing the following palatability categories: 1) Did not taste the study drug, 2) Tasted drug with score \> 60 to 100, 3) Tasted drug with score 40 to 60, and 4) Tasted drug with score of 0 to \< 40.

Time frame: Day 1