Clinical Trial Results:
A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Pharmacokinetics, Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed Dose Combination in Adolescents and Children with Chronic HCV Infection
Summary
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EudraCT number |
2018-000480-87 |
Trial protocol |
DE GB PL IT |
Global end of trial date |
19 Feb 2020
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Results information
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Results version number |
v2(current) |
This version publication date |
14 Oct 2020
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First version publication date |
29 Aug 2020
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Other versions |
v1 |
Version creation reason |
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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-367-1175
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001822-PIP01-15 | ||
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 |
19 Feb 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Feb 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate the steady-state pharmacokinetics (PK) and confirm the age-appropriate dose of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection.
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Protection of trial subjects |
The protocol and consent/assent forms were 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 Jan 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Italy: 13
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
United Kingdom: 4
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Worldwide total number of subjects |
21
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EEA total number of subjects |
21
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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) |
21
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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 study sites in Europe. The first participant was screened on 28 January 2019. The last study visit occurred on 19 February 2020. | ||||||
Pre-assignment
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Screening details |
The study was terminated because EMA granted Gilead a waiver for SOF/VEL/VOX in children less than 12 years old. Cohorts 2 and 3 were not enrolled. As per the protocol, participants could have received 8 or 12 weeks of treatment, depending on their prior treatment and disease status, however all participants received treatment for 8 weeks. | ||||||
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 |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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SOF/VEL/VOX FDC | ||||||
Arm description |
Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
SOF/VEL/VOX FDC
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Investigational medicinal product code |
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Other name |
Vosevi ®
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
400/100/100 mg administered once daily
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Baseline characteristics reporting groups
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Reporting group title |
SOF/VEL/VOX FDC
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Reporting group description |
Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SOF/VEL/VOX FDC
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Reporting group description |
Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets. |
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End point title |
Pharmacokinetic (PK) Parameter: AUCtau of SOF, GS-331007 (Metabolite of SOF), VEL, and VOX [1] | ||||||||||||||||
End point description |
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). For participants with separate consent to participate in the optional intensive PK substudy, intensive serial PK blood samples were collected at Week 2 or Week 4. Sparse PK samples were collected from all participants at Weeks 1, 2, 4, and end of treatment/Week 8. Plasma concentration data from all PK samples (intensive and sparse) were combined and used to generate PK parameters of SOF, GS-331007, VEL, and VOX for all participants using a population PK modeling approach.
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End point type |
Primary
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End point timeframe |
Sparse PK Sample (all participants): At Weeks 1 and 8 at any time, Weeks 2 and 4 (predose and between 15 minutes and 4 hours postdose). Intensive PK Sample [PK Substudy (N=14)]: Week 2 or Week 4 (0 (predose), 0.5, 1, 2, 3, 4, 6, 8, and 12 hours postdose).
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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 | ||||||||
End point description |
Treatment-emergent Adverse Events (TEAE) were defined as events that met 1 or both of the following criteria as any AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of study drug. It also includes the AEs that leads to premature discontinuation of study drug. The Safety Analysis Set included participants who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | ||||||||
End point description |
SVR was defined as hepatitis C virus (HCV RNA) < Lower limit of quantification (LLOQ) (ie, < 15 IU/mL) 12 weeks after discontinuation of the study drug. The Full Analysis Set included all adolescent participants 12 to < 18 years old who were enrolled into the study and took at least 1 dose of study drug (SOF/VEL/VOX FDC).
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End point type |
Secondary
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End point timeframe |
Posttreatment Week 12
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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 4 Weeks After Discontinuation of Therapy (SVR4) | ||||||||
End point description |
SVR is defined was HCV RNA < LLOQ (ie, < 15 IU/mL) 4 weeks after discontinuation of the study drug. Participants in the Full Analysis Set were analysed.
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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 24 Weeks After Discontinuation of Therapy (SVR24) | ||||||||
End point description |
SVR is defined was HCV RNA < LLOQ (ie, < 15 IU/mL) 24 weeks after discontinuation of the study drug. Participants in the Full Analysis Set were analysed.
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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 Overall Virologic Failure | ||||||||
End point description |
Overall Virologic Failure comprises of on-treatment virologic failure and relapse. On-treatment virologic failure (breakthrough, rebound, and nonresponse) and relapse were defined as follows: Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), Rebound (confirmed > 1 log10IU/mL increase in HCV RNA from nadir while on treatment), or Nonresponse (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) and Relapse (confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on treatment visit). Participants in the Full Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Up to 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 on Treatment | ||||||||||||||||
End point description |
Percentage of participants with HCV RNA < LLOQ (15 IU/mL) while on treatment by analysis visit. Participants in the Full Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Weeks 1, 2, 4, and 8
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX During Treatment | ||||||||
End point description |
Plasma samples were collected and stored for potential HCV sequencing. Impact on the treatment outcomes of SVR12 and SVR24 were observed during the study. Baseline nonstructural protein (NS)3, NS5A, and NS5B deep sequencing analysis was performed for all participants. Sequencing for the HCV NS5A and NS5B regions was performed for all enrolled participants at baseline and for participants with virologic failure. Resistance Analysis Population was defined as all participants in the Safety Analysis Set with a virologic outcome. No on-treatment virologic breakthrough or relapse was observed. Therefore, no participants qualified for resistance testing.
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End point type |
Secondary
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End point timeframe |
Up to End of Treatment (Week 8)
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Who Developed Viral Resistance to SOF, VEL, and/or VOX When Treatment is Discontinued | ||||||||
End point description |
Plasma samples were collected and stored for potential HCV sequencing. Impact on the treatment outcomes of SVR12 and SVR24 were observed during the study. Baseline nonstructural protein (NS)3, NS5A, and NS5B deep sequencing analysis was performed for all participants. Sequencing for the HCV NS5A and NS5B regions was performed for all enrolled participants at baseline and for participants with virologic failure. Resistance Analysis Population was defined as all participants in the Safety Analysis Set with a virologic outcome. No on-treatment virologic breakthrough or relapse was observed through posttreatment Week 12 or posttreatment Week 24.
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End point type |
Secondary
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End point timeframe |
Up to Posttreatment Week 24
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No statistical analyses for this end point |
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End point title |
Change in HCV RNA from Day 1 Through End of Treatment | ||||||||||||||||
End point description |
Participants in the Full Analysis Set with available data were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Weeks 1, 2 ,4, and 8
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Alanine Aminotransferase (ALT) Normalization | ||||||||||||||||||
End point description |
ALT normalization was defined as ALT > upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit. Participants in the Full Analysis Set with available data were analysed. It includes participants with ALT >ULN at Baseline.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Week 1, 2, 4, 8, and Posttreatment/Follow-up Week 4 (FU-4)
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Height Percentiles as a Measurement of Growth and Development | ||||||||||||||||
End point description |
An age- and sex-specific percentile was derived for each weight, height, and body mass index (BMI) measurement according to the statistical analysis system (SAS) program available on the Centers for Disease Control and Prevention (CDC) website using the year 2000 growth charts. Participants in the Safety Analysis Set with available data were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Weeks 1, 2, 4, 8, FU - 4, Posttreatment/Follow-up Week 12 (FU-12), and Posttreatment/Follow-up Week 24 (FU-24)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Weight Percentiles as a Measurement of Growth and Development | ||||||||||||||||
End point description |
An age- and sex-specific percentile was derived for each weight, height, and body mass index (BMI) measurement according to the statistical analysis system (SAS) program available on the Centers for Disease Control and Prevention (CDC) website using the year 2000 growth charts. Participants in the Safety Analysis Set with available data were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Weeks 1, 2, 4, 8, FU-4, FU-12, and FU-24
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No statistical analyses for this end point |
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End point title |
Number of Participants by Tanner Stage Assessment as a Measurement of Growth and Development | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Tanner Pubertal Staging were assessed for pubic hair growth and genitalia development (males) and for pubic hair growth and breast development (females) in stages 1 to 5. It was used to evaluate the onset and progression of pubertal changes from stage 1 (pre-pubertal) to stage 5 (adult). If a participant had reached Tanner stage 5, no further assessments were done. Pubic hair growth: Tanner stages (1: No hair, 2: Downy hair, 3: Coarse and curly hair, 4: Adult-like hair quality; 5: Hair extends to medial surface of the thighs); Breast development: Tanner stages (1: No glandular tissue, 2: Breast bud forms,3: More elevated, outside areola, 4: Increased breast size,5: Final adult-size breasts); Genitalia development: Tanner stages (1: Testes, scrotum, and penis about same size, 2: Enlargement of scrotum and testes, Penis (10.5-12.5); 3: Enlargement of penis (11.5-14); 4: Penis size (13.5-15); 5: Genitalia adult in size and shape). Participants in the Safety Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Weeks 8, FU-12, and FU-24
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Radiographic Bone Age Assessment as a Measurement of Growth and Development | ||||||||||||
End point description |
For radiographic bone age assessment, a single x-ray of the left wrist, hand, and fingers was performed and assessed by changes from baseline through end of treatment period. Participants in the Safety Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Week 8
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No statistical analyses for this end point |
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End point title |
Change from Baseline in C-Type Collagen Sequence (CTX) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development | ||||||||||||
End point description |
Fasting blood samples for baseline values for bone age biomarkers CTX and change from baseline were recorded. Participants in the Safety Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); FU-24
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No statistical analyses for this end point |
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End point title |
Change from Baseline in Procollagen Type 1 N-Terminal Propeptide (P1NP) Bone Turn-Over Biochemical Marker as a Measurement of Growth and Development | ||||||||||||
End point description |
Fasting blood samples for baseline values for bone age biomarkers P1NP and change from baseline were recorded. Participants in the Safety Analysis Set with available data were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); FU-24
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No statistical analyses for this end point |
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End point title |
Percentage of Participants in Each Swallowability Category of Able to Swallow or Unable to Swallow SOF/VEL/VOX 400/100/100 mg Size Tablets | ||||||||||||
End point description |
Swallowability for SOF/VEL/VOX FDC placebo to match (PTM) tablets was summarized based on the participants present in each swallowability category of Able to Swallow or Unable to Swallow a placebo tablet on one occasion during screening until Day 1. Participants in the Safety Analysis Set were analysed.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1)
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With Acceptability Questionnaire Responses as assessed by the Study Participant | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A questionnaire was administered to participants to assess acceptability, including palatability, of the formulation. Acceptability and palatability were assessed by questions about how the study drug tasted, how easy it was to swallow the study drug, and also at the end of treatment about how it was to take the study drug and, as they all received a single tablet daily, how they felt about the number of tablets they had to swallow.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1); Week 8
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With Acceptability Questionnaire Responses as assessed by the Parent/Legal Guardian | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A questionnaire was administered to the parent/legal guardian of participants to assess acceptability, including palatability, of the formulation. Acceptability and palatability were assessed by questions about how the study drug tasted, how easy it was to swallow the study drug, about how it was to take the study drug and, as they all received a single tablet daily, how they felt about the number of tablets they had to swallow.
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End point type |
Secondary
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End point timeframe |
Week 8
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No statistical analyses for this end point |
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End point title |
Neuropsychiatric Assessments Based on Questionnaire as Completed by Participant | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by all participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better health-related quality of life (HRQOL). A positive change from end of treatment period indicates improvement. Participants in the Full Analysis Set with available data were analysed.
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End point type |
Secondary
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End point timeframe |
Weeks 8, FU-12, and FU-24
|
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|
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No statistical analyses for this end point |
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End point title |
Neuropsychiatric Assessments Based on Questionnaire as Completed by Parent/Legal Guardian | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by the parent/ legal guardian of the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from end of treatment period indicates improvement. Participants in the Full Analysis Set were analysed.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Weeks 8, FU-12, and FU-24
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
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No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Neuropsychiatric Assessments as Completed by Participant | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by all the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It was presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analysed.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1); Weeks 8, FU-12, and FU-24
|
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|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Neuropsychiatric Assessments as Completed by Parent/Legal Guardian | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Neuropsychiatric safety assessment was done using the Pediatric Quality of Life (PedsQL™ 4.0 SF15). The PedsQL™ 4.0 SF15 Questionnaires was completed by the parent/ legal guardian of the participants. It is a comprehensive and widely used patient-reported outcome survey designed to measure health-related quality of life in healthy children and adolescents. It is presented for each of the 4 domains of the SF-15 (physical functioning, emotional functioning, social functioning, and school functioning), the psychosocial health summary (emotional, social, and school functioning domains), physical health summary and the Total Score. Total scores as well as each of the subscale scores are transformed on a scale from 0 to 100. Higher scores in each case indicate better HRQOL. A positive change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analysed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1); Weeks 8, FU-12, and FU-24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
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Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
First dose date up to the last dose date (maximum: 8 Weeks) plus 30 days.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
The Safety Analysis Set included participants who received at least 1 dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL/VOX FDC
|
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Reporting group description |
Direct-acting antiviral (DAA) - naive participants without cirrhosis (12 to < 18 years old) received sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) fixed-dose (FDC) combination (400/100/100 mg tablet) orally once daily in nonfasting state for 8 weeks. A single placebo to match tablet was administered during screening until Day 1 to confirm the participant was able to swallow SOF/VEL/VOX 400/100/100 mg tablets. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
27 Mar 2019 |
- The approximate amount of blood drawn at each visit was reduced to align with the pediatric EMA guidance “Guideline on the Investigation
of Medicinal Products in the Term and Preterm Neonate” dated 25 June 2009.
- Weight related inclusion criteria were added for the PK substudy to align with the pediatric EMA guidance “Guideline on the Investigation of
Medicinal
Products in the Term and Preterm Neonate” dated 25 June 2009.
- Clarification was provided regarding the possible impact of the study drug on P-glycoprotein (P-gp), breast cancer resistance protein (BCRP),
and organic anion-transporting polypeptide (OATP)1B1, OATP1B3, or OATP2B1 substrates, as described in the Investigator Brochure.
- Details regarding dose calculations for Cohorts 2 and 3 (aged 3 to < 12 years old) were added.
- Changes to the list of disallowed medications and concomitant medications to be used with caution were made to align with Vosevi EU
summary of product characteristics. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |