Clinical Trials Register

Summary
EudraCT Number:	2017-003338-94
Sponsor's Protocol Code Number:	AI444-423
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-03-14
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

Spain - AEMPS

A.2

EudraCT number

2017-003338-94

A.3

Full title of the trial

Open-Label, Single-Arm Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Daclatasvir (DCV) in Combination with Sofosbuvir (SOF) in Children from 3 to less than 18 Years of Age with GT-1 to -6 Chronic Hepatitis C (CHC) Infection

Ensayo abierto y con un solo grupo para evaluar la farmacocinética, la
seguridad y la eficacia de daclatasvir (DCV) en combinación con sofosbuvir
(SOF) en niños de entre 3 y menos de 18 años con infección por los
genotipos del 1 al 6 del virus de la hepatitis C crónica (HCC)

A.3.1

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

A study to determine how effect and safe Daclatasvir plus Sofosbuvir treatment is for children aged between 3-18 years of age with Hepatitis C.

Estudio para determinar el grado de eficacia y seguridad del tratamiento de
daclatasvir en combinación con sofosbuvir en niños con hepatitis C de
entre 3 y menos de 18 años.

A.4.1

Sponsor's protocol code number

AI444-423

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/311/2016

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bristol-Myers Squibb International Corporation
B.1.3.4	Country	Belgium
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	Bristol-Myers Squibb International Corporation
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bristol-Myers Squibb International Corporation
B.5.2	Functional name of contact point	GCT-SU
B.5.3	Address:
B.5.3.1	Street Address	Parc de l'Alliance - Avenue de Finlande, 4
B.5.3.2	Town/ city	Braine-l'Alleud
B.5.3.3	Post code	1420
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+34900 150 160
B.5.6	E-mail	clinical.trials@bms.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	Daklinza 60 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
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	Daclatasvir 60mg Film Coated Tablet (Clinical Formulation)
D.3.2	Product code	BMS-790052-05
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	DACLATASVIR DIHYDROCHLORIDE
D.3.9.2	Current sponsor code	BMS-790052- 05/DCV
D.3.9.3	Other descriptive name	DACLATASVIR
D.3.9.4	EV Substance Code	SUB34092
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	60
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.IMP: 2
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	No
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	Daclatasvir Dihydrochloride 20mg Chewable Tablet Paediatric formulation
D.3.4	Pharmaceutical form	Chewable tablet
D.3.4.1	Specific paediatric formulation	Yes
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	DACLATASVIR DIHYDROCHLORIDE
D.3.9.2	Current sponsor code	BMS-790052- 05/DCV
D.3.9.3	Other descriptive name	DACLATASVIR
D.3.9.4	EV Substance Code	SUB34092
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	20
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.IMP: 3
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	Sovaldi 400 mg Film-coated tablet
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd
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	Sofosbuvir 400 mg Film Coated Tablet
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.3.9.3	Other descriptive name	SOFOSBUVIR
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.3.11 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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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

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 (CHC) Infection

Infección por el virus de la hepatitis C crónica (HCC)

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C (CHC) Infection

Infección por el virus de la hepatitis C crónica (HCC)

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	20.1
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 PK profile of DCV in combination with SOF in children and adolescents aged 3 to <18 years of age

Evaluar el perfil FC de daclatasvir (DCV) en combinación con sofosbuvir
(SOF) en niños y adolescentes de entre 3 y menos de 18 años.

E.2.2

Secondary objectives of the trial

- To assess the safety and tolerability of the DCV+SOF regimen in pediatric participants
- To determine the proportion of participants with SVR12
- To evaluate genotypic substitution(s) associated with virologic failure
- To assess the acceptability and palatability for the age-appropriate chewable tablet formulation, and acceptability for adult film-coated tablet

— Evaluar la seguridad y la tolerabilidad de la pauta posológica de DCV +
SOF en participantes pediátricos.
— Determinar la proporción de participantes con RVS12.
— Evaluar la/s sustitución/es genotípica/s relacionada/s con el fracaso
virológico.
— Evaluar si la formulación de comprimidos masticables adecuada a la
edad resulta aceptable y de sabor agradable, y si resultan aceptables los
comprimidos recubiertos con película para adultos.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Participant/participant’s legal representative must provide written Informed Consent, and participants Assent when applicable
2) 3 to < 18 years of age on Day 1 of study treatment
3) ≥ 10 kg at Day 1
4) Chronic HCV infection GT-1 to -6 with HCV RNA ≥ 1,000 IU/mL at Screening
5) Non-cirrhotic
6) HCV-treatment naive or treatment experienced, with the exception of previous exposure to SOF and/or any NS5A inhibitors

1) El representante legal del participante / participante debe
proporcionar un Consentimiento informado por escrito y el
consentimiento de los participantes cuando corresponda
2) De entre 3 y menos de 18 años en el dia 1 de tratamiento del studio
3) Mayor o iguel a 10 kgr en el dia 1 de tratamiento
4) Infección crónica por los genotipos del 1 al 6 del virus de la HCC,
confirmada por presencia de ARN del VHC ≥ 1,000 UI / ml en la
selección
5) No cirrótico
6) Que no han recibido tratamiento previo para el VHC o que ya han
recibido tratamiento a excepción de la exposición previa a SOF y/o a
cualquiera de los inhibidores de NS5A.

E.4

Principal exclusion criteria

a) Mixed genotype HCV infections
b) Evidence of an ongoing medical condition contributing to chronic liver disease other than HCV
c) Evidence of cirrhosis, either compensated or decompensated
d) Positive serological test for chronic HBV-infection (HBsAg+) and/or HIV-infection
e) Inability to tolerate oral medication

a) Infecciones por genotipos mixtos del VHC.
b) Indicios de una afección en curso que contribuye a una enfermedad
hepática crónica distinta de la provocada por el VHC
c) Indicios de cirrosis, ya sea compensada o descompensada.
d) Prueba serológica con resultado positivo para la infección por el virus
de la HBC (HBsAg+) y/o para la infección por el VIH.
e) Incapacidad para tolerar la medicación oral.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetic parameters (Cmin, Cmax, Tmax, AUC (TAU), CLT/F) for DCV derived from plasma concentration versus time data on Day 10 (± 3 days)

Los parámetros farmacocinéticos (Cmín., Cmáx., Tmáx., ABC [τ], CLT/F)
para DCV procedentes de la concentración plasmática frente a los datos de tiempo del día 10 (±3 días) en un intervalo de administración.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 10 (± 3 days)

El día 10 (±3 días)

E.5.2

Secondary end point(s)

- Frequencies of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation of
study therapy, AEs by intensity, and laboratory abnormalities by toxicity grade on treatment and
during follow-up
- Proportion of participants with HCV RNA <LLOQ (TD or TND) at post-treatment follow-up Week 12
- Frequencies of NS5A and NS5B resistance-associated variants (RAVs) emergent at the time of virologic failure on treatment and during follow-up in nonresponders
- Summary of responses from questionnaire assessing acceptability and palatability at Day 1, Week 4, and Week 12

- Las frecuencias de los acontecimientos adversos graves (AAG), los
acontecimientos adversos (AA) que provocaron la interrupción del
tratamiento del estudio, los AA por intensidad y las anomalías analíticas
por grado de toxicidad durante el tratamiento y el periodo de
seguimiento.
— La proporción de participantes con ARN del VHC <límite inferior de
cuantificación (LLOQ) (objetivo identificado [TD] o no identificado
[TND]) en la semana 12 del seguimiento tras el tratamiento.
— La frecuencia de las variantes relacionadas con la resistencia (RAV)
NS5A y NS5B surgidas en el momento del fracaso virológico en el
tratamiento y durante el seguimiento de aquellos pacientes que no
respondan al tratamiento.
— El resumen de las respuestas del cuestionario que evalúa el grado de
aceptación y si el sabor resulta agradable (el día 1, la semana 4 y la
semana 12).

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints are outlined above for each endpoint

Los puntos temporales de cada criterio de valoración aparecen descritos anteriormente.

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

Yes

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

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

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

Yes

E.8.1.7.1

Other trial design description

Ensayo de cohorte descendente

Descending age cohort trial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Germany

Poland

Romania

Spain

Taiwan

E.8.7

Trial has a data monitoring committee

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

La ultima visita del ultimo paciente

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

Number of subjects for this age range:

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

For minors, a legally acceptable representative (per local legislation) must sign the ICF. The explicit wish of a minor, capable of assessing the study information forming an opinion, at any time should be considered by the investigator.

Para menores, un representante legalmente aceptable (según la legislación local) debe firmar la HIP.El deseo explícito de un menor, capaz de evaluar la información del studio, en cualquier momento debe ser considerado por el investigador.

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)

Participants will be followed for 12 weeks to assess sustained virologic response at Post-treatment Week 12 (SVR) and then for an additional 2 years as long-term follow-up to assess SVR, durability of response, long-term safety, and the persistence of resistance variants in non-responders. At the end of the study, BMS will not continue to provide study treatment unless BMS chooses to extend the study. The investigator should ensure that the participant receives appropriate standard of care.

Se seguirá a participantes durante 12 semanas para evaluar respuesta virológica sostenida en semana 12 posterior al tratamiento(RVS),luego durante 2 años adicionales como seguimiento largo plazo para evaluar la RVS,durabilidad de respuesta,seguridad a largo plazo y persistencia de variantes de resistencia en no respondedores.Al final de estudio,BMS no brindará tratamiento de estudio a menos que BMS decida extender estudio.El investigador debe asegurar al participante reciba la atención adecuada.

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

2018-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-04-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-09-17

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