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Trial record 1 of 1 for:    NCT02175758
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Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection

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ClinicalTrials.gov Identifier: NCT02175758
Recruitment Status : Completed
First Posted : June 26, 2014
Results First Posted : April 30, 2019
Last Update Posted : April 30, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.


Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: SOF Drug: RBV Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 7, 2014
Actual Primary Completion Date : June 21, 2018
Actual Study Completion Date : September 13, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 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.
Drug: SOF
SOF administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977

Drug: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®




Primary Outcome Measures :
  1. For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF) [ 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 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  2. 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 ]
  3. For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.


Secondary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

  4. For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

  5. For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough [ Time Frame: Up to 24 weeks ]
    Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment.

  6. For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse [ Time Frame: Up to Posttreatment Week 24 ]
    Viral relapse was defined as having confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

  7. 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) ]
  8. 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) ]
  9. For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization [ 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 ]
    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.

  10. 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 ]
  11. 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 ]
  12. For the Treatment Phase, Number of Male 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 ]
    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.

  13. 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 ]
    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.

  14. 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 ]
    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.

  15. 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 ]
    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.

  16. 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 [ Time Frame: Day 1 ]
    Participants were asked if they were able to taste the SOF oral granules.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02175758


  Hide Study Locations
Locations
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United States, California
Los Angeles, California, United States
San Francisco, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Florida
Gainesville, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, New York
New York, New York, United States
United States, Ohio
Cincinnati, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Fort Worth, Texas, United States
United States, Washington
Seattle, Washington, United States
United States, West Virginia
Morgantown, West Virginia, United States
Australia, New South Wales
Westmead, New South Wales, Australia
Australia, Victoria
Melbourne, Victoria, Australia
Australia
New Lambton Heights, Australia
Belgium
Brussels, Belgium
Germany
Wuppertal, Nordrhein-westfalen, Germany
Berlin, Germany
Italy
Bologna, Italy
Firenze, Italy
Milano, Italy
Padova, Italy
San Giovanni Rotondo, Italy
Torino, Italy
New Zealand
Auckland, New Zealand
Russian Federation
Moscow, Russian Federation
Novokuznetsk, Russian Federation
Saint-Petersburg, Russian Federation
Tolyatti, Russian Federation
United Kingdom
Birmingham, United Kingdom
Leeds, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Original  [PDF] December 20, 2013
Study Protocol: Amendment 1  [PDF] February 10, 2014
Study Protocol: Amendment 2  [PDF] March 14, 2014
Study Protocol: Amendment 3  [PDF] October 10, 2014
Study Protocol: Amendment 4  [PDF] November 12, 2014
Study Protocol: Amendment 5  [PDF] May 29, 2015
Study Protocol: Amendment 6  [PDF] February 26, 2016
Statistical Analysis Plan  [PDF] May 24, 2018


Publications of Results:
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
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
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.
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.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02175758     History of Changes
Other Study ID Numbers: GS-US-334-1112
2014-002283-32 ( EudraCT Number )
First Posted: June 26, 2014    Key Record Dates
Results First Posted: April 30, 2019
Last Update Posted: April 30, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis C
Virus Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents