Clinical Trial Results:
A Phase 2, Open-label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed Dose Combination in the Treatment of Hepatitis C Virus (HCV) Infection in Pediatric Subjects Undergoing Cancer Chemotherapy
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Summary
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EudraCT number |
2018-003741-42 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
03 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Aug 2019
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First version publication date |
14 Aug 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-US-337-1904
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02868242 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Gilead Sciences
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Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
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Public contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Scientific contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Feb 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Nov 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Feb 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objectives of this study were to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) infection in pediatric participants who are undergoing cancer chemotherapy.
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Protection of trial subjects |
The protocol and consent/assent form was submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements.
This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Aug 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Egypt: 19
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Worldwide total number of subjects |
19
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
19
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at one study site in Egypt. The first participant was screened on 28 August 2016. The last study visit occurred on 03 February 2019. | ||||||
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Pre-assignment
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Screening details |
24 participants were screened. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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LDV/SOF | ||||||
Arm description |
LDV/SOF 90/400 mg fixed dose combination (FDC) orally once daily for 12 weeks | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Ledipasvir/Sofosbuvir
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Investigational medicinal product code |
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Other name |
LDV/SOF; Harvoni®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
90/400 mg FDC orally once daily for 12 weeks
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Baseline characteristics reporting groups
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Reporting group title |
LDV/SOF
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Reporting group description |
LDV/SOF 90/400 mg fixed dose combination (FDC) orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LDV/SOF
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Reporting group description |
LDV/SOF 90/400 mg fixed dose combination (FDC) orally once daily for 12 weeks | ||
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End point title |
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [1] | ||||||||
End point description |
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 50 IU/mL) at 12 weeks after stopping study treatment. Full Analysis Set included participants who took at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Posttreatment Week 12
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical comparison was planned or performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event [2] | ||||||||
End point description |
Safety Analysis Set included participants who took at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
First dose date up to Week 12
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical comparison was planned or performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with HCV RNA < LLOQ at 4 Weeks After Discontinuation of Therapy (SVR4) | ||||||||
End point description |
SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Posttreatment Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24) | ||||||||
End point description |
SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Posttreatment Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HCV RNA < LLOQ While on Treatment | ||||||||||||||||
End point description |
Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Weeks 1, 4, 8 and 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
HCV RNA Change From Baseline/Day 1 | ||||||||||||||||
End point description |
Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline; Weeks 1, 4, 8, 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of Participants With Virologic Failure | ||||||||
End point description |
Participants in the Full Analysis Set were analyzed.
Virologic failure was defined as:
- On-treatment virologic failure:
-- Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
-- Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
-- Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
- Virologic relapse:
-- Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit
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End point type |
Secondary
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End point timeframe |
Baseline up to Posttreatment Week 24
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events: First dose date up to Week 12 plus 30 days; All-Cause Mortality: First dose date up to Posttreatment Week 24
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Adverse event reporting additional description |
Safety Analysis Set included participants who took at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
LDV/SOF
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Reporting group description |
LDV/SOF 90/400 mg FDC orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Jun 2017 |
• Added: HBcAb, HBsAb on Screening visit
• Added text regarding sample collection for HBV DNA testing at Day 1, Weeks 4, 8, and 12, or Early Termination, and all post-treatment visits and that HBV DNA will only be tested in subjects who are HBcAb+ at screening.
• Clarified timing of Fibrotest (Screening, Baseline, Week 12, Post Treatment Week 12, Post Treatment Week 24, and ESDD as applicable) and APRI (Screening, Week 12, and Post Treatment Week 4, and ESDD as applicable)
• Changed APRI calculation at Post Treatment Week 24 to Week 12 and Post Treatment Week 4
• Changed the Inclusion Criteria from Weight ≥ 45 kg to Weight ≥ 35 kg
• Clarified HBV Infection in Exclusion Criteria: Hepatitis B surface antigen positive (HBsAg+) at screening
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
