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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02249182




Registration number
NCT02249182
Ethics application status
Date submitted
23/09/2014
Date registered
25/09/2014
Date last updated
2/03/2020

Titles & IDs
Public title
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Scientific title
A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Secondary ID [1] 0 0
2014-003578-17
Secondary ID [2] 0 0
GS-US-337-1116
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 - LDV/SOF
Treatment: Drugs - RBV

Experimental: 12 to < 18 Years Old - Participants between 12 to \< 18 years of age weighing = 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

* HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

* HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks

Experimental: 6 to < 12 Years Old - Participants between 6 to \< 12 years of age weighing = 17 kg and \< 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

* HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

* HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks

Experimental: 3 to < 6 Years Old - Participants between 3 to \< 6 years of age weighing = 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing \< 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

* HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

* HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
* HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
* HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks


Treatment: Drugs: LDV/SOF
LDV/SOF FDC administered orally once daily

Treatment: Drugs: RBV
Ribavirin (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), LDV, and SOF
Timepoint [1] 0 0
Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10
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
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
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 10
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 12 Weeks After Discontinuation of Therapy (SVR12)
Timepoint [4] 0 0
Posttreatment Week 12
Secondary outcome [5] 0 0
For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
Timepoint [5] 0 0
Posttreatment Week 24
Secondary outcome [6] 0 0
For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough
Timepoint [6] 0 0
Up to 24 weeks
Secondary outcome [7] 0 0
For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse
Timepoint [7] 0 0
Up to Posttreatment Week 24
Secondary outcome [8] 0 0
For the Treatment Phase, Change From Baseline in HCV RNA
Timepoint [8] 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 [9] 0 0
For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment
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)
Secondary outcome [10] 0 0
For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization
Timepoint [10] 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 [11] 0 0
For the Treatment Phase, Change From Baseline in Height
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, Change From Baseline in Weight
Timepoint [12] 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 [13] 0 0
For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair
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 Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development
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 Pubic Hair
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, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development
Timepoint [16] 0 0
Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24
Secondary outcome [17] 0 0
Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1
Timepoint [17] 0 0
Day 1
Secondary outcome [18] 0 0
Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1
Timepoint [18] 0 0
Day 1

Eligibility
Key inclusion criteria
Key

* Consent of parent or legal guardian required
* Chronic HCV infection
* Screening laboratory values within defined thresholds

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 individual's treatment, assessment or compliance with the protocol.
* Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
* Clinical hepatic decompensation (i.e., 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
5/11/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/08/2018
Sample size
Target
Accrual to date
Final
226
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Newcastle
Recruitment hospital [2] 0 0
- Westmead
Recruitment hospital [3] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
- Newcastle
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
United States of America
State/province [19] 0 0
West Virginia
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
United Kingdom
State/province [21] 0 0
England
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Scotland

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the PK Lead-in Phase of the study is to evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.

The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The primary objective of the Treatment Phase is to evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.

During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow tablets.
Trial website
https://clinicaltrials.gov/study/NCT02249182
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. 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. Hepatology 2016;64 (S1): 436A
Schwarz K, Murray KF, Rosenthal P, Bansal S, Lin CH, Ni L, et al. High Rates of SVR12 in Adolescents Treated with the Combination of Ledipasvir/Sofosbuvir. J Hepatol 2016; 64 (2): S184-S185
K.F. Murray, W. Balistreri, S. Bansal, S. Whitworth, H. Evans, R.P. Gonzalez-Peralta, et al. Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6-11 years old with chronic hepatitis C infection. J Hepatol 2017;66: S33-S62
Balistreri WF, Murray KF, Rosenthal P, Bansal S, Lin CH, Kersey K, Massetto B, Zhu Y, Kanwar B, German P, Svarovskaia E, Brainard DM, Wen J, Gonzalez-Peralta RP, Jonas MM, Schwarz K. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017 Aug;66(2):371-378. doi: 10.1002/hep.28995. Epub 2017 Jun 19.
Younossi ZM, Stepanova M, Balistreri W, Schwarz K, Murray KF, Rosenthal P, Bansal S, Hunt S. Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir. J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):112-116. doi: 10.1097/MPG.0000000000001754.
Begley R, Meng A, Massetto B, Shao J, Ling J, and Mathias A. Pharmacokinetics of Once Daily Sofosbuvir or Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 3 to <6 Years Old. Hepatology 2018;68 (S1): 582A.
Schwarz KB, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Children 3 to <6 Years Old with Chronic Hepatitis C Virus Infection. Hepatology 2018;68 (S1): 116A-117A.
Murray KF, Balistreri WF, Bansal S, Whitworth S, Evans HM, Gonzalez-Peralta RP, Wen J, Massetto B, Kersey K, Shao J, Garrison KL, Parhy B, Brainard DM, Arnon R, Gillis LA, Jonas MM, Lin CH, Narkewicz MR, Schwarz K, Rosenthal P. Safety and Efficacy of Ledipasvir-Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6-11. Hepatology. 2018 Dec;68(6):2158-2166. doi: 10.1002/hep.30123. Epub 2018 Nov 17.
Schwarz KB, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, Mittal N, Massetto B, Brainard DM, Hsueh CH, Shao J, Parhy B, Narkewicz MR, Rao GS, Whitworth S, Bansal S, Balistreri WF. Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C. Hepatology. 2020 Feb;71(2):422-430. doi: 10.1002/hep.30830. Epub 2019 Aug 19.
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/NCT02249182