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

Hepatitis C Virus Infection Clinical Trial

Official title:

A Phase 2, Open-Label, Multicenter, Multi-cohort, Single-Arm Study to Investigate the Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175758
• Other study ID #: GS-US-334-1112
• Secondary ID: 2014-002283-32
• Status: Completed
• Phase: Phase 2
• Start date: July 7, 2014
• Est. completion date: September 13, 2018

Study information

• Verified date: April 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: September 13, 2018
• Est. primary completion date: June 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis C
• Hepatitis C Virus Infection
• Infection
• Virus Diseases

Intervention

Drug:
• SOF
SOF administered orally once daily
• RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Germany,  Italy,  New Zealand,  Russian Federation,  United Kingdom, 

References & Publications (6)

Garrison KL, Mathias A, Kersey K, Kanwar B, Ni L, Jain A, et al. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 6 to <12 Years Old [Poster 878]. American Association for the Study of Liver Diseases (AAS

Kirby B, German P, Kanwar B, Ni L, Lakatos I, Ling J, Mathias A. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Adolescents [Poster 1707]. American Association for the Study of Liver Diseases (AASLD); 2015 November 13-

Rosenthal P, Schwarz KB, Gonzales-Peralta RP, Lin CH, Kelly DA, Nightingale S, et al. Sofosbuvir + Ribavirin for 12 or 24 Weeks Is Safe and Effective in Children 3 to <12 Years Old with Genotype 2 or Genotype 3 Chronic Hepatitis C Infection. Hepatology 20

Schwarz KB, Rosenthal P, Gonzales-Peralta RP, Jonas MM, Balistreri WF, Lin CH, et al. Sofosbuvir + Ribavirin for 12 or 24 Weeks Is Safe and Effective in Adolescents with Genotype 2 or Genotype 3 Chronic Hepatitis C Infection. Hepatology 2016; 63 (Suppl 1)

Wirth S, Rosenthal P, Gonzalez-Peralta RP, Jonas MM, Balistreri WF, Lin CH, Hardikar W, Kersey K, Massetto B, Kanwar B, Brainard DM, Shao J, Svarovskaia E, Kirby B, Arnon R, Murray KF, Schwarz KB. Sofosbuvir and ribavirin in adolescents 12-17 years old wi — View Citation

Younossi ZM, Stepanova M, Schwarz KB, Wirth S, Rosenthal P, Gonzalez-Peralta R, Murray K, Henry L, Hunt S. Quality of life in adolescents with hepatitis C treated with sofosbuvir and ribavirin. J Viral Hepat. 2018 Apr;25(4):354-362. doi: 10.1111/jvh.12830 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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
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		Up to 24 weeks
Primary	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.	Posttreatment Week 12
Secondary	For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA		Baseline; Weeks 1, 2, 4, 8, and 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
Secondary	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase		Up to Day 7
Secondary	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.	Posttreatment Week 4
Secondary	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.	Posttreatment Week 24
Secondary	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.	Up to 24 weeks
Secondary	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.	Up to Posttreatment Week 24
Secondary	For the Treatment Phase, Change From Baseline in HCV RNA		Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
Secondary	For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment		Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
Secondary	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.	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
Secondary	For the Treatment Phase, Change From Baseline in Height		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
Secondary	For the Treatment Phase, Change From Baseline in Weight		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
Secondary	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.	Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary	For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development	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.	Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary	For the Treatment Phase, Number of Female 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.	Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary	For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development	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.	Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary	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.	Day 1