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

NCT ID: NCT02175758

Last Updated: 2019-04-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-07

Study Completion Date

2018-09-13

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatitis C Virus Infection

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

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

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.

Group Type EXPERIMENTAL

SOF

Intervention Type DRUG

SOF administered orally once daily

RBV

Intervention Type DRUG

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

Interventions

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SOF

SOF administered orally once daily

Intervention Type DRUG

RBV

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

Intervention Type DRUG

Other Intervention Names

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Sovaldi® GS-7977 REBETOL®

Eligibility Criteria

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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

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
Minimum Eligible Age

3 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Los Angeles, California, United States

Site Status

San Francisco, California, United States

Site Status

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

Site Status

Gainesville, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

New York, New York, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Nashville, Tennessee, United States

Site Status

Dallas, Texas, United States

Site Status

Fort Worth, Texas, United States

Site Status

Seattle, Washington, United States

Site Status

Morgantown, West Virginia, United States

Site Status

Westmead, New South Wales, Australia

Site Status

Melbourne, Victoria, Australia

Site Status

New Lambton Heights, , Australia

Site Status

Brussels, , Belgium

Site Status

Wuppertal, North Rhine-Westphalia, Germany

Site Status

Berlin, , Germany

Site Status

Bologna, , Italy

Site Status

Florence, , Italy

Site Status

Milan, , Italy

Site Status

Padua, , Italy

Site Status

San Giovanni Rotondo, , Italy

Site Status

Torino, , Italy

Site Status

Auckland, , New Zealand

Site Status

Saint Petersburg, Russian Federation, Russia

Site Status

Moscow, , Russia

Site Status

Novokuznetsk, , Russia

Site Status

Saint Petersburg, , Russia

Site Status

Tolyatti, , Russia

Site Status

Birmingham, , United Kingdom

Site Status

Leeds, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Germany Italy New Zealand Russia United Kingdom

References

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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

Reference Type 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

Reference Type 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.

Reference Type 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.

Reference Type RESULT
PMID: 28543053 (View on PubMed)

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.

Reference Type RESULT
PMID: 29193603 (View on PubMed)

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.

Reference Type 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.

Reference Type DERIVED
PMID: 31222783 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

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Document Type: Study Protocol: Amendment 2

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Document Type: Study Protocol: Amendment 3

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Document Type: Study Protocol: Amendment 4

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Document Type: Study Protocol: Amendment 5

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Document Type: Study Protocol: Amendment 6

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-002283-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-334-1112

Identifier Type: -

Identifier Source: org_study_id

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