Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection

Gilead Sciences106 enrolled

Overview

This study will have two parts as follows: The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir (SOF) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety and tolerability of 7 days of dosing of SOF+ribavirin (RBV) in HCV-infected pediatric participants. The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate SOF dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of SOF+RBV for 12 or 24 weeks in pediatric participants with genotype 2 or 3 HCV infection, respectively.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

106

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 genotype 2 or 3 * Screening laboratory values within defined thresholds * PK Lead-in only: all individuals must be treatment naive Key Exclusion Criteria: * History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol * Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus * Clinical hepatic decompensation (ie, 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 (37)

Unnamed facility

Los Angeles, California, United States

Unnamed facility

San Francisco, California, United States

Unnamed facility

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

Unnamed facility

Gainesville, Florida, United States

Unnamed facility

Atlanta, Georgia, United States

Unnamed facility

Indianapolis, Indiana, United States

Unnamed facility

Baltimore, Maryland, United States

Unnamed facility

Boston, Massachusetts, United States

Unnamed facility

New York, New York, United States

Unnamed facility

Cincinnati, Ohio, United States

...and 27 more locations

Outcomes

Primary Outcomes

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

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

Time frame: 6 to < 18 years of age: predose, 0.5, 1, 2, 3, 4, 8, and 12 hours postdose on Day 7; 3 to < 6 years of age: predose, 2, 4, 8, and 12 hours postdose on Day 7

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

For the Treatment Phase, Percentage of Participants With SVR at 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

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, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)

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 7

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 \< LLOQ at 4 weeks after stopping study treatment.

Time frame: Posttreatment Week 4

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. One participant in the 3 to \< 6 Years Old 12 Weeks group had ALT \> ULN at Baseline, but had no other available data.

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

For the Treatment Phase, Palatability of SOF Granules at Day 1 as Assessed by the Percentage of Participants Able/Unable to Taste the SOF Oral Granules

Participants were asked if they were able to taste the SOF oral granules.

Time frame: Day 1