Study to Investigate Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) Fixed Dose Combination (FDC) in Adolescents and Children With Chronic Hepatitis C Virus (HCV) Infection

NCT03820258 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-367-11752018-000480-87
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 10

Brief Summary

The primary objective of this study is to evaluate the steady-state pharmacokinetics (PK) and confirm the age-appropriate dose of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection.

Conditions

Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX

  AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For participants with separate consent to participate in the optional intensive PK substudy, intensive serial PK blood samples were collected at Week 2 or Week 4. Sparse PK samples were collected from all participants at Weeks 1, 2, 4, and end of treatment/Week 8. Plasma concentration data from all PK samples (intensive and sparse) were combined and used to generate PK parameters of SOF, GS-331007, VEL, and VOX for all participants using a population PK modeling approach.

  Sparse PK Sample (all participants): At Weeks 1 and 8 at any time, Weeks 2 and 4 (predose and between 15 minutes and 4 hours postdose). Intensive PK Sample [PK Substudy (N=14)]: Week 2 or Week 4 (0 (predose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose)

Secondary Outcomes (23)

• Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event

  First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days

• Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

  Posttreatment Week 12

• Percentage of Participants With HCV RNA < LLOQ 4 Weeks After Discontinuation of Therapy (SVR4)

  Posttreatment Week 4

• Percentage of Participants With HCV RNA < LLOQ 24 Weeks After Discontinuation of Therapy (SVR24)

  Posttreatment Week 24

• Percentage of Participants With Overall Virologic Failure

  Up to Posttreatment Week 24

Study Arms (6)

Experimental: Cohort 1 (12 to < 18 years old), 8 Weeks

EXPERIMENTAL

Direct-acting antiviral (DAA)-naive participants without cirrhosis in Cohort 1 (12 to \< 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 8 weeks.

Drug: SOF/VEL/VOX

Experimental: Cohort 1 (12 to < 18 years old), 12 Weeks

EXPERIMENTAL

DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 1 (12 to \< 18 years old) will receive SOF/VEL/VOX FDC 400/100/100 mg for 12 weeks.

Drug: SOF/VEL/VOX

Experimental: Cohort 2 (6 to < 12 years old), 8 Weeks

EXPERIMENTAL

DAA-naive participants without cirrhosis in Cohort 2 (6 to \< 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.

Drug: SOF/VEL/VOX

Experimental: Cohort 2 (6 to < 12 years old), 12 Weeks

EXPERIMENTAL

DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 2 (6 to \< 12 years old) will receive SOF/VEL/VOX FDC for 12 weeks.

Drug: SOF/VEL/VOX

Experimental: Cohort 3 (3 to < 6 years old), 8 Weeks

EXPERIMENTAL

DAA-naive participants without cirrhosis in Cohort 3 (6 to \< 12 years old) will receive SOF/VEL/VOX FDC for 8 weeks.

Drug: SOF/VEL/VOX

Experimental: Cohort 3 (3 to < 6 years old), 12 Weeks

EXPERIMENTAL

DAA-naive participants with cirrhosis or DAA-experienced participants with or without cirrhosis in Cohort 3 (3 to \< 6 years old) will receive SOF/VEL/VOX FDC for 12 weeks.

Drug: SOF/VEL/VOX

Interventions

SOF/VEL/VOX DRUG

Administered once daily with food.

Also known as: Vosevi ®

Experimental: Cohort 1 (12 to < 18 years old), 12 Weeks; Experimental: Cohort 1 (12 to < 18 years old), 8 Weeks; Experimental: Cohort 2 (6 to < 12 years old), 12 Weeks; Experimental: Cohort 2 (6 to < 12 years old), 8 Weeks; Experimental: Cohort 3 (3 to < 6 years old), 12 Weeks; Experimental: Cohort 3 (3 to < 6 years old), 8 Weeks

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Consent of parent or legal guardian required
• Chronic HCV infection
• Screening laboratory values within defined thresholds
• Individuals must have a determination of prior treatment status:
• DAA-naive is defined as either:
• Treatment naive with no prior exposure to any interferon (IFN), ribavirin (RBV), or approved or experimental HCV-specific DAA
• Treatment experienced with an IFN-based regimen and no prior exposure to an approved or experimental HCV-specific DAA
• DAA-experienced is defined as prior exposure to a regimen including any DAA (eg, non-structural protein (NS)3/4A protease inhibitor, NS5A inhibitor, or NS5B nucleotide/nucleoside inhibitor)

You may not qualify if:

• 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 human immunodeficiency virus (HIV), acute hepatitis A virus (HAV) or hepatitis B virus (HBV)
• Clinical hepatic decompensation (eg, clinical ascites, encephalopathy, and/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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (10)

SOS-intraSOC Epatologia

Florence, 50139, Italy

Location

Servizio di Epatologia e Nutrizione Pediatrica

Milan, 20122, Italy

Location

US Infettivologia Pediatrica-Polo Universitario

Milan, 20157, Italy

Location

UOS Epatologia Pediatrica

Napoli, 80131, Italy

Location

UOSD Epatologia

San Giovanni Rotondo, 71013, Italy

Location

Wojewodzki Szpital

Bydgoszcz, 85-030, Poland

Location

Med Polonia

Poznan, 60-693, Poland

Location

Uniwersytecki Szpital Kliniczny im.

Wroclaw, 50-368, Poland

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

Kings Healthcare NHS Trust Hospital

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

sofosbuvir velpatasvir voxilaprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 29, 2019
• Study Start: January 28, 2019
• Primary Completion: December 4, 2019
• Study Completion: February 19, 2020
• Last Updated: October 23, 2020
• Results First Posted: August 31, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

IT (5); GB (2); PL (3)