Clinical Trials Register

Summary
EudraCT Number:	2018-002735-26
Sponsor's Protocol Code Number:	CC-10004-PSA-013
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-11-16
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

2018-002735-26

A.3

Full title of the trial

A PHASE 4, MULTICENTER, RANDOMIZED, DOUBLEBLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN SUBJECTS WITH EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS DESPITE INITIAL STABLE TREATMENT WITH EITHER NSAIDS AND/OR ≤ 1 CONVENTIONAL SYNTHETIC DMARD

ESTUDIO DE FASE 4, MULTICÉNTRICO, ALEATORIZADO, DOBLE CIEGO, CONTROLADO CON PLACEBO Y DE GRUPOS PARALELOS PARA EVALUAR LA EFICACIA Y LA SEGURIDAD DE APREMILAST (CC-10004) EN PACIENTES CON ARTRITIS PSORIÁSICA OLIGOARTICULAR TEMPRANA A PESAR DE UN TRATAMIENTO ESTABLE INICIAL CON AINE Y/O ≤1 FARME SINTÉTICO CONVENCIONAL

A.3.1

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

A clinical study to test the effects of a apremilast compared to placebo for the treatment of patients with Psoriatic Arthritis with less than 2 years of duration and up to 4 joints involved, despite stable treatment with either non-steroidal anti-inflammatory drugs (ie aspirin, ibuprofen and naproxyn) and /or ≤ 1 non-biologic disease-modifying antirheumatic drugs (methotrexate OR sulfasalazine).

Estudio clínico para evaluar los efectos de apremilast en comparación con un placebo para el tratamiento de pacientes con artritis psoriásica de menos de 2 años de duración y con un máximo de 4 articulaciones afectadas, a pesar de un tratamiento estable con antiinflamatorios no esteroideos (es decir, ácido acetilsalicílico, ibuprofeno y naproxeno) y/o ≤ 1 fármaco antirreumático modificador de la enfermedad no biológico (metotrexato O sulfasalazina).

A.3.2

Name or abbreviated title of the trial where available

FOREMOST

A.4.1

Sponsor's protocol code number

CC-10004-PSA-013

A.5.4

Other Identifiers

Name:

IND

Number:

101761

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

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	+34914229000
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 BV
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	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 10 mg
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 BV
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	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 20 mg
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 BV
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	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 30 mg
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
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
D.8 Placebo: 2
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
D.8 Placebo: 3
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

EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS

ARTRITIS PSORIÁSICA OLIGOARTICULAR TEMPRANA

E.1.1.1

Medical condition in easily understood language

Mild form of joint inflammation affecting individuals with the skin disorder, psoriasis.

Forma leve de inflamación articular que afecta a personas con trastornos cutáneos, psoriasis.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10037160
E.1.2	Term	Psoriatic arthritis
E.1.2	System Organ Class	100000004859

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 efficacy of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +- NSAIDs and/or csDMARDs in subjects with early oligoarticular psoriatic arthritis (PsA), assessed by modified MDA (MDA-Joints).

Evaluar la eficacia de apremilast 30 mg dos veces al día +/- AINE y/o FARMEsc frente a un placebo +/- AINE y/o FARMEsc en pacientes con APs oligoarticular temprana, mediante la actividad mínima de la enfermedad (MDA) modificada (MDA-articulaciones).

E.2.2

Secondary objectives of the trial

- To evaluate the impact of treatment with apremilast 30 mg BID + NSAIDs and/or csDMARDs vs. Placebo NSAIDs and/or csDMARDs on disease activity in subjects with early oligoarticular PsA.
- To evaluate the impact of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +-NSAIDs and/or csDMARDs on patient-reported outcomes (PROs) in subjects with early oligoarticular PsA.
- To evaluate the safety and tolerability of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +-NSAIDs and/or csDMARDs in subjects with early oligoarticular PsA.

· Evaluar el efecto del tratamiento con apremilast 30 mg dos veces al día +/- AINE y/o FARMEsc frente a un placebo +/- AINE y/o FARMEsc en la actividad de la enfermedad en pacientes con APs oligoarticular temprana.
· Evaluar el efecto de apremilast 30 mg dos veces al día +/- AINE y/o FARMEsc frente a un placebo +/- AINE y/o FARMEsc en los resultados comunicados por el paciente (RCP) en pacientes con APs oligoarticular temprana.
· Evaluar la seguridad y la tolerabilidad de apremilast 30 mg dos veces al día +/- AINE y/o FARMEsc frente a un placebo +/- AINE y/o FARMEsc en pacientes con APs oligoarticular temprana.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject is a male or female, ≥ 18 years at time of consent.
2. Subjects must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject must have a documented diagnosis of PsA (by any criteria) of ≥ 3 months but 24 months duration at the time of the Screening Visit.
5. Subject meets the CASPAR (Appendix B) criteria for PsA at the Screening Visit.
6. Subject must have a total number of swollen joints greater than 1 and equal or less than 4 (> 1 but 4 swollen joints) at the Screening Visit and confirmed prior to randomization at the Baseline Visit.
7. Subject must have a total number of tender joints greater than 1 and equal or less than 4 (> 1 but 4 tender joints) at Screening and confirmed prior to randomization at the Baseline Visit.
8. Subjects taking oral glucocorticosteroids must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 4 weeks prior to the Baseline Visit (Section 8.1).
9. For all regions, the local Regulatory Label for treatment with apremilast must be followed. For example, subjects in the EU must have had inadequate response or intolerance to a prior csDMARD.
10. Subjects taking 1 protocol-allowed csDMARD (methotrexate [MTX] or sulfasalazine [SSZ]) may enter the study provided that the duration of treatment is ≤6 months prior to the Baseline Visit and treatment is taken at a stable dose for at least 3 months prior to the Baseline Visit. See Permitted Medications (Section 8.1) for details describing dose criteria.
11. Subjects exposed to MTX or SSZ and stopped treatment due to intolerance or due to safety reasons may enter the study provided that treatment was stopped within 4 days of the Baseline Visit.
12. Subjects taking NSAIDs may enter the study provided that the dose is stable for at least 2 weeks prior to the Baseline Visit. Subjects may discontinue NSAIDs at any time up to and including the Baseline Visit, prior to study randomization.
13. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening and the Baseline Visit. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy; OR
Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

A female of childbearing potential is defined as a sexually mature female who: 1) has not undergone a
hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both
ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any
time during the preceding 24 consecutive months).
The female subject’s chosen form of contraception must be effective by the time the female subject is screened into the study (for example, hormonal contraception should be initiated at least 28 days before screening).

14. Must be in general good health (except for psoriatic arthritis) as judged by the Investigator, based on medical history, physical examination, and clinical laboratories. (Note: The definition of good health means a subject does not have uncontrolled significant comorbid conditions).

1. Varones y mujeres ≥ 18 años en el momento de la firma del consentimiento.
2. Los sujetos deben comprender y firmar voluntariamente un documento de consentimiento informado antes de que empiecen a realizarse las evaluaciones/procedimientos relacionados con el estudio.
3. El sujeto debe estar dispuesto a cumplir el calendario de visitas del estudio y los demás requisitos del protocolo y ser capaz de hacerlo.
4. El sujeto debe tener un diagnóstico documentado de APs (según cualquier criterio) con una duración de la enfermedad ≥ 3 meses pero ≤ 24 meses en el momento de la visita de selección.
5. El sujeto cumple los criterios CASPAR (apéndice B) de APs en la visita de selección.
6. El sujeto debe tener un número total de articulaciones inflamadas superior a 1 pero inferior o igual a 4 (> 1 y ≤4 articulaciones inflamadas) en la visita de selección, confirmadas antes de la aleatorización en la visita basal.
7. El sujeto debe tener un número total de articulaciones dolorosas superior a 1 pero inferior o igual a 4 (> 1 y ≤4 articulaciones dolorosas) en la visita de selección, confirmadas antes de la aleatorización en la visita basal.
8. Los sujetos que estén recibiendo glucocorticosteroides orales deberán haber recibido una dosis estable de prednisona ≤ 10 mg/día o equivalente durante al menos 4 semanas antes de la visita basal (sección 8.1).
9. En todas las regiones deberán seguirse las directrices reglamentarias locales para el tratamiento con apremilast. Por ejemplo, los sujetos de la UE deben haber tenido una respuesta insuficiente o intolerancia a un FARMEsc previo.
10. Los sujetos que estén tomando un FARMEsc permitido por el protocolo (metotrexato [MTX] o sulfasalazina [SSZ]) podrán participar en el estudio siempre que la duración del tratamiento sea ≤ 6 meses antes de la visita basal y que el tratamiento se haya tomado en una dosis estable durante al menos 3 meses antes de la visita basal. En la sección de Medicamentos permitidos (sección 8.1) puede consultar los detalles relativos a los criterios posológicos.
11. Los sujetos expuestos a MTX o SSZ que hayan interrumpido el tratamiento por intolerancia o por motivos de seguridad podrán participar en el estudio siempre que el tratamiento se haya interrumpido en los 4 días previos a la visita basal.
12. Los sujetos que tomen AINE podrán participar en el estudio siempre que la dosis se mantenga estable durante al menos 2 semanas antes de la visita basal. Los sujetos podrán suspender los AINE en cualquier momento hasta la visita basal, inclusive, antes de la aleatorización en el estudio.
13. Las mujeres en edad fértil (MEF)† deberán tener un resultado negativo en una prueba de embarazo realizada en las visitas de selección y basal. Mientras reciban el producto en investigación y durante al menos 28 días después de tomar la última dosis del producto en investigación, las MEF que mantengan relaciones sexuales con riesgo de embarazo deberán utilizar una de las opciones anticonceptivas aprobadas que se describen a continuación:
Opción 1: cualquiera de los siguientes métodos muy eficaces: anticonceptivo hormonal (oral, inyectable, implante, parche transdérmico, anillo vaginal), dispositivo intrauterino (DIU), ligadura de trompas o vasectomía de la pareja.
Opción 2: preservativo masculino o femenino (preservativo de látex o preservativo sin látex NO fabricado con membranas naturales [animales] [por ejemplo, de poliuretano]) MÁS un método de barrera adicional: (a) diafragma con espermicida, (b) capuchón cervical con espermicida o (c) esponja anticonceptiva con espermicida.
Una mujer en edad fértil se define como una mujer sexualmente madura que: 1) no se ha sometido a una histerectomía (extirpación quirúrgica del útero) ni a una ovariectomía bilateral (extirpación quirúrgica de ambos ovarios) o 2) no ha presentado un estado posmenopáusico durante al menos 24 meses seguidos (es decir, ha tenido la regla en algún momento durante los 24 meses previos consecutivos).
El método anticonceptivo escogido por la paciente debe ser completamente eficaz cuando comience la fase de selección para el estudio (es decir, los anticonceptivos hormonales deberán empezar a administrarse al menos 28 días antes de la selección).
14. Buen estado general de salud (excepto por la artritis psoriásica) según el criterio del investigador, basándose en la historia clínica, la exploración física y los análisis clínicos. (Nota: por buena salud se entiende que el sujeto no tiene enfermedades concomitantes importantes no controladas).

E.4

Principal exclusion criteria

1. Prior use of >1 cs DMARD.
2. Prior exposure to a JAK-inhibitor and/or a biologic DMARD.
3. Use of intra-articular (IA) glucocorticoid injection within 8 weeks before the Baseline Visit.
4. Use of leflunomide within 12 weeks of randomization. Subjects who stopped leflunomide and completed 11 days of treatment with cholestyramine (8 g, 3 x daily) prior to the Baseline Visit may enter the study.
5. Prior use of cyclosporine.
6. Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
7. Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
8. History of clinically significant or uncontrolled disease (as determined by the Investigator), including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
9. Prior history of suicide attempt at any time in the subject’s lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
10. Pregnant or breast feeding.
11. Active substance abuse or a history of substance abuse within 6 months prior to Screening.
12. History of allergy to any component of the investigational product.
13. History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
14. Active tuberculosis or a history of incompletely treated tuberculosis.
15. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed and the infection cured, at least 4 weeks prior to Screening and no new or recurrent infections prior to the Baseline Visit.
16. Malignancy or history of malignancy or myeloproliferative or lymphoproliferative disease within the past 3 years, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas.
17. Major surgery (including joint surgery) within 8 weeks prior to the Screening Visit or planned major surgery within 6 months following the Baseline Visit.
18. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or fibromyalgia.
19. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, rheumatoid arthritis [RA], ankylosing spondylitis, Lyme disease), which confounds the ability to interpret data from the study.
20. Erythrodermic, guttate, or generalized pustular psoriasis at randomization.

1. Uso previo de más de un FARMEsc.
2. Exposición previa a un inhibidor de JAK o a un FARME biológico.
3. Uso de glucocorticoides en inyección intraarticular (IA) en las 8 semanas previas a la visita basal.
4. Uso de leflunomida en las 12 semanas previas a la aleatorización. Podrán participar en el estudio los sujetos que hayan interrumpido la leflunomida y hayan completado 11 días de tratamiento con colestiramina (8 g tres veces al día) antes de la visita basal.
5. Uso previo de ciclosporina.
6. Tratamiento previo con apremilast o participación en un estudio clínico de apremilast.
7. Uso de cualquier fármaco en investigación en las 4 semanas anteriores a la visita basal o el periodo correspondiente a 5 semividas farmacocinéticas/farmacodinámicas, si se conoce (lo que suponga más tiempo).
8. Antecedentes de enfermedad de importancia clínica o no controlada (según lo determinado por el investigador), incluida la presencia de anomalías analíticas, que entrañe un riesgo inaceptable para el sujeto en caso de participar en el estudio.
9. Antecedentes de intento de suicidio en cualquier momento de la vida del sujeto antes de la firma del consentimiento informado o enfermedad psiquiátrica importante con necesidad de hospitalización en los 3 años anteriores a la firma del consentimiento informado.
10. Embarazo o lactancia.
11. Abuso actual de sustancias o antecedentes de abuso de sustancias en los seis meses previos a la selección.
12. Antecedentes de alergia a cualquiera de los componentes del producto en investigación (PEI).
13. Antecedentes de seropositividad para el virus de la inmunodeficiencia humana (VIH) o inmunodeficiencia congénita o adquirida (por ejemplo, inmunodeficiencia variable común).
14. Tuberculosis activa o antecedentes de tuberculosis tratada de forma incompleta.
15. Infecciones bacterianas con necesidad de tratamiento con antibióticos orales o inyectables, o infecciones víricas o fúngicas importantes, en las 4 semanas previas a la selección. El tratamiento de estas infecciones debe haber finalizado y la infección debe estar curada como mínimo 4 semanas antes de la selección, y no deben haberse producido infecciones nuevas ni recurrentes antes de la visita basal.
16. Neoplasia maligna o antecedentes de neoplasia maligna o enfermedad mieloproliferativa o linfoproliferativa en los 3 últimos años, excepto carcinoma de piel basocelular o espinocelular in situ tratado (es decir, curado).
17. Intervención de cirugía mayor (incluida la cirugía articular) en las 8 semanas previas a la visita de selección o intervención de cirugía mayor programada en los 6 meses siguientes a la visita basal.
18. Enfermedad reumática autoinmunitaria distinta de la APs, incluidas, entre otras: lupus eritematoso sistémico (LES), enfermedad mixta del tejido conjuntivo (EMTC), esclerodermia, polimiositis o fibromialgia.
19. Antecedentes o presencia de artropatía inflamatoria distinta de la APs (por ejemplo, gota, artritis reactiva, artritis reumatoide [AR], espondilitis anquilosante o enfermedad de Lyme), que dificulte la capacidad de interpretar los datos del estudio.
20. Psoriasis eritrodérmica, en gotas o pustulosa generalizada en el momento de la aleatorización.

E.5 End points

E.5.1

Primary end point(s)

MDA-Joints: Proportion of subjects who achieved a clinical state of minimal disease activity defined MDA-Joints. Subjects must achieve <=1 SJC and TJC, plus 3 out of 5 of the remaining cut-off values (BSA <= 3%; Patient pain (VAS) <= 15; Patient global disease activity (VAS) <= 20; HAQ <= 0.5; Tender entheseal points <= 1 (based on Leeds Enthesitis Index - LEI).

MDA-Articulaciones: proporción de sujetos que alcancen un estado clínico de actividad mínima de la enfermedad definida por la MDA-articulaciones. Los sujetos deben alcanzar ≤1 articulaciones inflamadas y ≤1 articulaciones dolorosas, más 3 de los 5 valores de corte restantes (SC ≤ 3%; evaluación del dolor por el paciente (EAV) ≤ 15; evaluación global de la actividad de la enfermedad por el paciente (EAV) ≤ 20; HAQ ≤ 0,5; puntos de entesis dolorosos ≤ 1 (conforme al Índice de entesitis de Leeds, LEI).

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

Semana 24

E.5.2

Secondary end point(s)

- cDAPSA remission or low disease activity
- Swollen Joint Count (SJC) <= 1
- Tender Joint Count (TJC) <= 1
- Patient's global assessment of disease activity
- Patient's assessment of pain
- Change from Baseline in the Psoriatic Arthritis Impact of Disease 12-item for clinical trials (PsAID-12) questionnaire.
- PASDAS good and moderate response

- Remisión cDAPSA o actividad baja de la enfermedad
- Número de articulaciones inflamadas ≤ 1
- Número de articulaciones dolorosas ≤ 1
- Evaluación global de la actividad de la enfermedad por el paciente
- Evaluación del dolor por el paciente
- Variación con respecto al momento basal en el Cuestionario de 12 preguntas sobre el impacto de la artritis psoriásica (PsAID-12) para ensayos clínicos
- Respuesta PASDAS buena y moderada

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 24

Semana 24

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

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

Austria

Belgium

Canada

France

Germany

Italy

Netherlands

Russian Federation

Spain

United Kingdom

United States

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

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 fecha de la última visita del último paciente que complete el seguimiento posterior al tratamiento, o la fecha de recepción de los últimos datos correspondientes al último paciente que sean necesarios para los análisis principales, secundarios o exploratorios, tal como se establece en el protocolo, lo que ocurra 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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

287

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

190

F.4.2.2

In the whole clinical trial

330

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)

This is left at the discretion of the treating physician. As Otezla (apremilast) is an approved, marketed product, subjects who benefit from treatment with apremilast during the CC-10004-PSA-013 study will have the option to receive Otezla in accordance with the marketing authorization in their respective country. Subjects are also required to meet a specific Inclusion Criterion to support compliance with the local marketing authorization.

Esto quedará a criterio del médico responsable del tratamiento. Dado que Otezla (apremilast) es un producto aprobado y comercializado, los sujetos que se beneficien del tratamiento con apremilast durante el estudio CC-10004-PSA-013 tendrán la opción de recibir Otezla de acuerdo con la autorización de comercialización en su país. Los sujetos también deberán cumplir un criterio de inclusión específico para asegurar el cumplimiento de la autorización de comercialización local.

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

2019-01-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-01-24

P. End of Trial
P.	End of Trial Status	Ongoing

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