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

NCT02175758 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-334-11122014-002283-32
• Study Type: interventional
• Target: 106
• Locations: 8 countries
• Sites: 37

Brief 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.

Conditions

Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (16)

• 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)

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

  Up to Day 7

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

  Posttreatment Week 4

• For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

  Posttreatment Week 24

• For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough

  Up to 24 weeks

Study Arms (6)

12 to < 18 Years Old, SOF+RBV 12 Weeks (GT 2)

EXPERIMENTAL

Participants between 12 to \< 18 years of age with genotype (GT) 2 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.

Drug: SOF; Drug: RBV

12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3)

EXPERIMENTAL

Participants between 12 to \< 18 years of age with genotype 3 HCV infection weighing ≥ 45 kg will receive SOF (1 x 400 mg tablet, 4 x 100 mg tablets, or 8 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.

Drug: SOF; Drug: RBV

6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2)

EXPERIMENTAL

Participants between 6 to \< 12 years of age with genotype 2 HCV infection weighing ≥ 17 kg and \< 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 12 weeks.

Drug: SOF; Drug: RBV

6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)

EXPERIMENTAL

Participants between 6 to \< 12 years of age with genotype 3 HCV infection weighing ≥ 17 kg and \< 45 kg will receive SOF (2 x 100 mg tablets or 4 x 50 mg oral granules based on swallowability assessment during screening) plus RBV (up to 1400 mg) for 24 weeks.

Drug: SOF; Drug: RBV

3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2)

EXPERIMENTAL

Participants between 3 to \< 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 12 weeks and those weighing \< 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 12 weeks.

Drug: SOF; Drug: RBV

3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3)

EXPERIMENTAL

Participants between 3 to \< 6 years of age with genotype 2 HCV infection weighing ≥ 17kg will receive SOF (4 x 50 mg oral granules) plus RBV (up to 1400 mg) for 24 weeks and those weighing \< 17 kg will receive SOF (3 x 50 mg oral granules) + RBV (up to 1400 mg) for 24 weeks.

Drug: SOF; Drug: RBV

Interventions

SOF DRUG

SOF administered orally once daily

Also known as: Sovaldi®, GS-7977

12 to < 18 Years Old, SOF+RBV 12 Weeks (GT 2); 12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3); 3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2); 3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3); 6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2); 6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)

RBV DRUG

RBV oral solution or capsules will be administered orally in a divided daily dose based on weight

Also known as: REBETOL®

12 to < 18 Years Old, SOF+RBV 12 Weeks (GT 2); 12 to < 18 Years Old, SOF+RBV 24 Weeks (GT 3); 3 to < 6 Years Old, SOF+RBV 12 Weeks (GT 2); 3 to < 6 Years Old, SOF+RBV 24 Weeks (GT 3); 6 to < 12 Years Old, SOF+RBV 12 Weeks (GT 2); 6 to <12 Years Old, SOF+RBV 24 Weeks (GT 3)

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 genotype 2 or 3
• Screening laboratory values within defined thresholds
• PK Lead-in only: all individuals must be treatment naive

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 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (37)

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Los Angeles, California, United States

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San Francisco, California, United States

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

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Gainesville, Florida, United States

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Atlanta, Georgia, United States

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Indianapolis, Indiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Westmead, New South Wales, Australia

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Melbourne, Victoria, Australia

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New Lambton Heights, Australia

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Brussels, Belgium

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Wuppertal, North Rhine-Westphalia, Germany

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Berlin, Germany

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Bologna, Italy

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Florence, Italy

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Milan, Italy

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Padua, Italy

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San Giovanni Rotondo, Italy

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Torino, Italy

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Auckland, New Zealand

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Saint Petersburg, Russian Federation, Russia

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Moscow, Russia

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Novokuznetsk, Russia

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Saint Petersburg, Russia

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Tolyatti, Russia

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Birmingham, United Kingdom

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Leeds, United Kingdom

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London, United Kingdom

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Related Publications (7)

• 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 13-17, San Francisco, USA. Hepatology 2015;62 (S1): 1040A-1041A

  RESULT

• 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 (AASLD); 2016 11-15 November; Boston, MA. Hepatology 2016;64 (S1): 436A

  RESULT

• 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): abstract 706.

  RESULT

• 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 with hepatitis C virus genotype 2 or 3 infection. Hepatology. 2017 Oct;66(4):1102-1110. doi: 10.1002/hep.29278. Epub 2017 Aug 26.

  PMID: 28543053 RESULT

• 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. Epub 2017 Dec 26.

  PMID: 29193603 RESULT

• 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 2018; 68 (Suppl 1): abstract 1844.

  RESULT

• Rosenthal P, Schwarz KB, Gonzalez-Peralta RP, Lin CH, Kelly DA, Nightingale S, Balistreri WF, Bansal S, Jonas MM, Massetto B, Brainard DM, Hsueh CH, Shao J, Parhy B, Davison S, Feiterna-Sperling C, Gillis LA, Indolfi G, Sokal EM, Murray KF, Wirth S. Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection. Hepatology. 2020 Jan;71(1):31-43. doi: 10.1002/hep.30821. Epub 2019 Aug 13.

  PMID: 31222783 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Sofosbuvir; Ribavirin

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

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 26, 2014
• Study Start: July 7, 2014
• Primary Completion: June 21, 2018
• Study Completion: September 13, 2018
• Last Updated: April 30, 2019
• Results First Posted: April 30, 2019

Record last verified: 2019-04

Locations

AU (3); US (16); RU (5); DE (2); NZ (1); BE (1); IT (6); GB (3)