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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02175758




Registration number
NCT02175758
Ethics application status
Date submitted
24/06/2014
Date registered
26/06/2014
Date last updated
30/04/2019

Titles & IDs
Public title
Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
Scientific 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
Secondary ID [1] 0 0
2014-002283-32
Secondary ID [2] 0 0
GS-US-334-1112
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C Virus Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SOF
Treatment: Drugs - RBV

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.

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.

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.

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.

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.

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.


Treatment: Drugs: SOF
SOF administered orally once daily

Treatment: Drugs: RBV
RBV oral solution or capsules will be administered orally in a divided daily dose based on weight
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF)
Timepoint [1] 0 0
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 outcome [2] 0 0
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase
Timepoint [2] 0 0
Up to 24 weeks
Primary outcome [3] 0 0
For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12)
Timepoint [3] 0 0
Posttreatment Week 12
Secondary outcome [1] 0 0
For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA
Timepoint [1] 0 0
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 outcome [2] 0 0
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase
Timepoint [2] 0 0
Up to Day 7
Secondary outcome [3] 0 0
For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4)
Timepoint [3] 0 0
Posttreatment Week 4
Secondary outcome [4] 0 0
For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
Timepoint [4] 0 0
Posttreatment Week 24
Secondary outcome [5] 0 0
For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough
Timepoint [5] 0 0
Up to 24 weeks
Secondary outcome [6] 0 0
For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse
Timepoint [6] 0 0
Up to Posttreatment Week 24
Secondary outcome [7] 0 0
For the Treatment Phase, Change From Baseline in HCV RNA
Timepoint [7] 0 0
Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
Secondary outcome [8] 0 0
For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment
Timepoint [8] 0 0
Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only)
Secondary outcome [9] 0 0
For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
Timepoint [9] 0 0
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 outcome [10] 0 0
For the Treatment Phase, Change From Baseline in Height
Timepoint [10] 0 0
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 outcome [11] 0 0
For the Treatment Phase, Change From Baseline in Weight
Timepoint [11] 0 0
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 outcome [12] 0 0
For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair
Timepoint [12] 0 0
Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary outcome [13] 0 0
For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development
Timepoint [13] 0 0
Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary outcome [14] 0 0
For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair
Timepoint [14] 0 0
Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary outcome [15] 0 0
For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development
Timepoint [15] 0 0
Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Day 1

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/09/2018
Sample size
Target
Accrual to date
Final
106
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Melbourne
Recruitment hospital [3] 0 0
- New Lambton Heights
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- New Lambton Heights
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
United States of America
State/province [14] 0 0
West Virginia
Country [15] 0 0
Belgium
State/province [15] 0 0
Brussels
Country [16] 0 0
Germany
State/province [16] 0 0
Nordrhein-westfalen
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Italy
State/province [18] 0 0
Bologna
Country [19] 0 0
Italy
State/province [19] 0 0
Firenze
Country [20] 0 0
Italy
State/province [20] 0 0
Milano
Country [21] 0 0
Italy
State/province [21] 0 0
Padova
Country [22] 0 0
Italy
State/province [22] 0 0
San Giovanni Rotondo
Country [23] 0 0
Italy
State/province [23] 0 0
Torino
Country [24] 0 0
New Zealand
State/province [24] 0 0
Auckland
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Moscow
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Novokuznetsk
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Saint-Petersburg
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Tolyatti
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Birmingham
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Leeds
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02175758
Trial related presentations / publications
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02175758