Clinical Trials Register

Summary
EudraCT Number:	2018-000480-87
Sponsor's Protocol Code Number:	GS-US-367-1175
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-02-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-000480-87

A.3

Full title of the trial

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

Studio di fase 2, in aperto, multicentrico, multi-coorte per valutare la farmacocinetica, la sicurezza e l’efficacia della combinazione a dose fissa di sofosbuvir/velpatasvir/voxilaprevir in adolescenti e bambini con infezione cronica da virus dell’epatite C (Hepatitis C virus, HCV)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

N/A

A.4.1

Sponsor's protocol code number

GS-US-367-1175

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/121/2016

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GILEAD SCIENCES INCORPORATED
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GILEAD SCIENCES INCORPORATED
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences International Ltd.
B.5.2	Functional name of contact point	Clinical Trials Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Granta Park
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441223897284
B.5.6	E-mail	clinical.trials@gilead.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vosevi 400 mg/100 mg/100 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences Ireland UC
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vosevi
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sofosbuvir
D.3.9.1	CAS number	1190307-88-0
D.3.9.2	Current sponsor code	GS-7977
D.3.9.4	EV Substance Code	SUB121170
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Velpatasvir
D.3.9.1	CAS number	1377049-84-7
D.3.9.2	Current sponsor code	GS-5816
D.3.9.4	EV Substance Code	SUB180213
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Voxilaprevir
D.3.9.1	CAS number	1535212-07-7
D.3.9.2	Current sponsor code	GS-9857
D.3.9.4	EV Substance Code	SUB185303
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Hepatitis C virus infection

Infezione cronica da virus dell’epatite C

E.1.1.1

Medical condition in easily understood language

Hepatitis C

Epatite C

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10019744
E.1.2	Term	Hepatitis C
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10008912
E.1.2	Term	Chronic hepatitis C
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the steady-state pharmacokinetics (PK) and confirm ageappropriate dose of SOF/VEL/VOX FDC in pediatric subjects with chronic HCV infection

Valutare la farmacocinetica (PK) allo stato costante e confermare la dose appropriata per età di sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in combinazione a dose fissa (FDC) nei soggetti pediatrici con infezione cronica da virus dell’epatite C (HCV)

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of SOF/VEL/VOX FDC in pediatric subjects with chronic HCV infection

To evaluate the antiviral efficacy of SOF/VEL/VOX FDC treatment in pediatric subjects with chronic HCV infection, as assessed by the proportion of pediatric subjects with sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12)

To evaluate the antiviral efficacy SOF/VEL/VOX FDC treatment in pediatric subjects with chronic HCV infection, as assessed by the
proportion of pediatric subjects with SVR 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)

To evaluate the proportion of pediatric subjects with virologic failure, including on-treatment virologic failure and relapse

To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment

Please refer to protocol for full list of secondary objectives of the trial.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenomics
Version: Original
Date: 08/02/2018
Title: NA
Objectives: To identify or validate genetic markers that may be predictive of the natural history of disease, response to therapy and/or tolerability of medical therapies through genetic discovery research (eg, pharmacogenomics), in subjects who provide their separate and specific consent

Farmacogenomica
Versione: Original
Data: 08/02/2018
Titolo: NA
Obiettivi: To identify or validate genetic markers that may be predictive of the natural history of disease, response to therapy and/or tolerability of medical therapies through genetic discovery research (eg, pharmacogenomics), in subjects who provide their separate and specific consent

E.3

Principal inclusion criteria

1) Subject or parent/ legal guardian able to provide written informed
consent prior to any screening evaluations. Willing to comply with study
requirements in accordance with IEC/local requirements and the
Investigator's discretion. Subject will provide assent, if possible.
2) 3 to < 18 years of age as determined at Day 1
3) Chronic HCV infection (= 6 months) as documented by prior medical
history or liver biopsy
4) HCV RNA = 1000 IU/mL at Screening
5) Subjects must have a determination of prior treatment status as
defined in protocol.
6) A negative serum pregnancy test is required at Screening and a
negative urine test is required at Day 1 for female subjects of
childbearing potential
7) Male subjects and female subjects of childbearing potential who
engage in heterosexual intercourse must agree to use protocol specified
method(s) of contraception
8) Lactating females must agree to discontinue nursing before the study
drug is administered
9) Subject must be able to comply with the dosing instructions for study
drug administration and be able to complete the study schedule of
assessments.

E.4

Principal exclusion criteria

1) Current or prior history of clinical hepatic decompensation (eg,
clinical ascites, encephalopathy, and/or variceal hemorrhage)
2) Any of the following laboratory parameters at Screening:
a) INR >1.2 x ULN
b) Platelets < 50,000/mm3
c) Albumin < 3.5 g/dL
d) ALT> 10 x ULN
e) AST > 10 x ULN
f) Direct bilirubin > 1.5 x ULN
g) Estimated glomerular filtration rate < 90 mL/min/1.73m2, as
calculated by the Schwartz formula
3) Chronic liver disease of a non-HCV etiology (eg, hemochromatosis,
Wilson's disease, alpha-1 antitrypsin deficiency)
4) Evidence of hepatocellular carcinoma or other malignancy (with
exception of certain resolved skin cancers)
5) Co-infection with human immunodeficiency virus (HIV), acute
hepatitis A virus (HAV) or hepatitis B virus (HBV) (hepatitis B surface
antigen [HBsAg] positive at Screening)
6) Current or prior history of any of the following:
a) Clinically significant illness (other than HCV) or any other major
medical disorder that may have interfered with subject treatment,
assessment, or compliance with the protocol; subjects currently under
evaluation for a potentially clinically significant illness (other than HCV)
are also excluded
b) Significant cardiac disease
c) Gastrointestinal malabsorption syndrome that may interfere with
absorption of orally administered medications
d) History of solid organ or bone marrow transplantation
e) Psychiatric hospitalization, suicide attempt, and/or a period of
disability as a result of their psychiatric illness within the last 5 years.
Subjects with psychiatric illness (without the prior mentioned
conditions) that is well controlled on a stable treatment regimen for at
least 6 months prior to enrollment or has not required medication in the
last 12 months may be included
7) Clinically relevant alcohol or drug abuse within 12 months of
Screening. A positive drug screen will exclude subjects unless it can be
explained by a prescribed medication; the diagnosis and prescription
must be approved by the investigator
8) Use of any prohibited concomitant medications
9) Investigational agents taken within the past 28 days (except with the
approval of the sponsor)
10) Known hypersensitivity to the study drug, the metabolites, or
formulation excipients

E.5 End points

E.5.1

Primary end point(s)

The appropriateness of the SOF/VEL/VOX FDC dose will be assessed by evaluating its steadystate PK. The primary PK endpoint is AUCtau of SOF, its major metabolite (GS-331007), VEL and VOX.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks post last treatment dose

E.5.2

Secondary end point(s)

1) Any AE leading to permanent discontinuation of study drug
2) The proportion of subjects with sustained virological response (SVR)
12 weeks after cessation of treatment (SVR12) is the key efficacy
endpoint
3) The proportion of subjects with HCV RNA < LLOQ at 4 or 24 weeks
after cessation of treatment (SVR4 and SVR24)
4) The proportion of subjects with virologic failure, including ontreatment
virologic failure and relapse
5) The proportion of subjects with HCV RNA < LLOQ on treatment
6) Emergence of viral resistance to SOF, VEL, and VOX during treatment
and treatment is discontinued
7) HCV RNA change from Day 1
8) Growth and development measurements including height and weight
percentiles, Tanner Stage, radiographic bone age and two bone turnover
biochemical markers (CTX and P1NP)
9) Acceptability, including palatability, and swallowability assessments
10) Neuropsychiatric assessments as measured by PedsQL™ Pediatric
Quality of Life survey

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints will be assessed on treatment or at 12 and 24 weeks following discontinuation of treatment

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatrics

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-12-18

P. End of Trial
P.	End of Trial Status	Completed

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