Clinical Trials Register

Summary
EudraCT Number:	2015-003314-24
Sponsor's Protocol Code Number:	CC-10004-PPSO-001
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:	2016-01-13
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

2015-003314-24

A.3

Full title of the trial

A Phase 2, Multicenter, Open-label Study to Assess the Safety, Tolerability and Pharmacokinetics of Apremilast (CC-10004) in Pediatric Subjects with Moderate to Severe Plaque Psoriasis

Estudio abierto y multicéntrico de fase 2 para evaluar la seguridad, tolerabilidad y farmacocinética de apremilast (CC-10004) en pacientes pediátricos con psoriasis en placas entre moderada y grave

A.3.1

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

A clinical trial to evaluate if apremilast is safe in children and adolescents with moderate to severe plaque psoriasis as well as assessing how apremilast is processed by the body, and to determine the appropriate dose for them

Un ensayo clínico para evaluar si apremilast es seguro en niños y adolescentes con psoriasis en placas entre moderada y grave, cómo se procesa en el organismo y definir la dosis adecuada

A.4.1

Sponsor's protocol code number

CC-10004-PPSO-001

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/167/2015

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Celgene Corporation
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	Celgene Corporation
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	Celgene Corporation
B.5.2	Functional name of contact point	ClinicalTrialDisclosure
B.5.3	Address:
B.5.3.1	Street Address	9225 Indian Creek Parkway, Suite 900
B.5.3.2	Town/ city	Overland Park, Kansas
B.5.3.3	Post code	66210
B.5.3.4	Country	United States
B.5.4	Telephone number	+1888-260-1599
B.5.5	Fax number	+1913-266-0394
B.5.6	E-mail	ClinicalTrialDisclosure@celgene.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	Otezla
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Apremilast
D.3.2	Product code	CC-10004
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	Apremilast
D.3.9.1	CAS number	608141-41-9
D.3.9.2	Current sponsor code	CC-10004
D.3.9.3	Other descriptive name	APREMILAST
D.3.9.4	EV Substance Code	SUB130837
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	10
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	Yes
D.2.1.1.1	Trade name	Otezla
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Apremilast
D.3.2	Product code	CC-10004
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	Apremilast
D.3.9.1	CAS number	608141-41-9
D.3.9.2	Current sponsor code	CC-10004
D.3.9.3	Other descriptive name	APREMILAST
D.3.9.4	EV Substance Code	SUB130837
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	Otezla
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Europe Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Apremilast
D.3.2	Product code	CC-10004
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	Apremilast
D.3.9.1	CAS number	608141-41-9
D.3.9.2	Current sponsor code	CC-10004
D.3.9.3	Other descriptive name	APREMILAST
D.3.9.4	EV Substance Code	SUB130837
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	30
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

Moderate to severe plaque psoriasis in adolescents (ages 12 to 17 years, inclusive) and in children (ages 6 to 11 years, inclusive).

Psoriasis en placas entre moderada y grave en adolescentes (edades de 12 a 17 años, ambas incluidas) y en niños (edades de 6 a 11 años, ambas incluidas).

E.1.1.1

Medical condition in easily understood language

Plaque psoriasis

Psoriasis en placas

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10071117
E.1.2	Term	Plaque psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10037153
E.1.2	Term	Psoriasis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to select a pediatric dose of apremilast based on the safety, tolerability, and PK of apremilast in adolescents and children with moderate to severe plaque psoriasis.

Seleccionar una dosis pediátrica de apremilast basándose en la seguridad, tolerabilidad y farmacocinética (FC) de apremilast (APR) en adolescentes y niños con psoriasis en placas entre moderada y grave.

E.2.2

Secondary objectives of the trial

The secondary objective is to evaluate the taste and acceptability of apremilast tablet using a faces Likert Scale.

Evaluar la palatabilidad y aceptabilidad del comprimido de apremilast utilizando una escala Likert de caras.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male or female 6 to 17 years of age with diagnosis of chronic plaque psoriasis

Pacientes de ambos sexos de entre 6 y 17 años diagnosticados con psoriasis en placas

E.4

Principal exclusion criteria

Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study or which places subject at unacceptable riskif he/she were to participate in the study

Afecciones médicas importantes, resultados anómalos en análisis de laboratorio, enfermedad psiquiátrica que impide al paciente participar en el estudio o que su inclusión pusiese en riesgo al paciente

E.5 End points

E.5.1

Primary end point(s)

Safety:
a.Adverse events (AEs)
b.Complete Physical examinations
c.Vital sign measurements
d.Height and weight
e.Clinical laboratory safety tests
f.12-lead electrocardiograms (ECGs)
g.Concomitant medications / procedures
h.Pregnancy testing for females of child-bearing potential
i.Hepatitis B and C testing

j.Pharmacokinetics:
-Maximum observed plasma concentration (Cmax)
- Time to Cmax (tmax)
- Area under the plasma concentration-time curve from time zero extrapolated to
infinity (AUC0-?)
- Area under the plasma concentration-time curve from time zero to 12 hours postdose (AUC0-12)
- Area under the plasma concentration-time curve from time zero to the last
quantifiable concentration (AUC0-t)
- Apparent total plasma clearance when dosed orally (CL/F)
- Apparent total volume of distribution when dosed orally, based on steady-state
(Vss/F) or the terminal phase (Vz/F)
- Terminal-phase elimination half-life (t1/2)
- CL/F
- Apparent total volume of distribution when dosed orally (V/F)
- Absorption rate constant (first-order; Ka)
- Lag (if applicable)

Seguridad:
a. Acontecimientos adversos (AA)
b. Exploraciones físicas
c. Medición de constantes vitales
d. Peso y altura
e. Análisis clínicos de seguridad de laboratorio
f. Electrocardiogramas (ECG) de 12 derivaciones
g. Medicación / procedimientos concomitantes
h. Pruebas de embarazo
i. Pruebas de hepatitis B y C

Farmacocinética
- Máxima concentración plasmática observada (Cmáx)
- Tiempo para Cmáx (tmáx)
- Área bajo la curva de concentración plasmática-tiempo desde tiempo cero extrapolada al infinito (ABC0-?)
- Área bajo la curva de concentración plasmática-tiempo desde tiempo cero hasta 12 horas tras la dosis (ABC0-12)
- Área bajo la curva de concentración plasmática-tiempo desde tiempo cero hasta la última concentración cuantificable (ABC0-t)
- Aclaramiento plasmático aparente total cuando se dosifica por vía oral (CL/F)
- Volumen aparente de distribución total cuando se dosifica por vía oral, basado en el estado estacionario (Vss/F) o la fase terminal (Vz/F)
- Vida media de eliminación de la fase terminal (t1/2)
- CL/F
- Volumen aparente de distribución total cuando se dosifica por vía oral (V/F)
- Constante de velocidad de absorción (primer orden; Ka)
- Demora (si corresponde)

E.5.1.1

Timepoint(s) of evaluation of this end point

a.After signing ICF and until 28 days after the last dose
b.Visit 1 and visit 13 (Abbreviated physical exam at all other visits)
c.At each visit from Visit 1 to Visit 12, at any unscheduled visit and at early termination visit
d.At every visit
e.At visits 1 and visit 2, each visit from visit 4 to visit 12, at any unscheduled visit and at early termination visit
f.At visit 1 and after the last dose of investigational product. If a subject withdraws from the study prior to entering the extension treatment period, an ECG should be completed at the Week 2 (Final PK) visit
g.Prior to the Week 102 visit
h.At all visits except Visit 3 (PK), Visit 13, and unscheduled visits
i.At screening
j.At Visit 2 and visit 3 (and Early Termination Visit if visit 3 is not done)

a- Tras la firma del HIP-CI y 28 días después de la última dosis
b. Visitas 1 y 13 (examen físico abreviado en el resto de las visitas)
c. En cada visita desde la 1 a la 12 y en cada visita no programada y en la visita de finalización prematura
d. En cada visita
e. En las visitas 1 y 2, visitas 4 hasta 12, en cada visita no programada y en la visita de finalización prematura
f. En la visita 1 y tras la última dosis del producto en investigación. Si un paciente abandona el estudio antes de la fase de extensión, se debe hacer un ECG en la visita 2 (FC final).
g. Antes de la visita de la semana 102
h. En todas las visitas excepto la 3 (FC), la 13 y las no programadas
i. En la visita de selección
En las visitas 2 y 3 (y la visita de finalización prematura si no se ha hecho la visita 3

E.5.2

Secondary end point(s)

Taste and acceptability of apremilast tablet

Palatabilidad y aceptabilidad del comprimido de apremilast

E.5.2.1

Timepoint(s) of evaluation of this end point

At Visit 2

En la visita 2

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

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability, taste and acceptability

Tolerabilidad, palatabilidad y aceptabilidad

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

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

Canada

Germany

Spain

United Kingdom

United States

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

The End of Trial is defined as either the date of the last visit of the last subject to complete the post treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date.

La finalización del estudio está definida como la fecha en la que tiene lugar la última visita del último paciente en la fase de seguimiento tras el tratamiento o la fecha de recepción del último corte de datos del último sujeto que se requiere para los análisis primarios, secundarios y exploratorios tal como se especifica en el protocolo, lo que suceda más tarde

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2016-01-13.

Yes

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

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)

The subject's treatment after ending participation in the trial will be at the discretion of the treating physician.

El tratamiento del sujeto tras finalizar su participación en el ensayo será a criterio del facultativo

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

2016-03-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-07-29

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IMP with orphan designation in the indication
Orphan Designation Number:
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