Clinical Trials Register

Summary
EudraCT Number:	2016-000191-21
Sponsor's Protocol Code Number:	M14-496
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:	2016-12-09
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

2016-000191-21

A.3

Full title of the trial

A Phase 4 open-label randomized controlled study COmparing the effectiveness of adalimumab iNTROduction and methotrexate dose escaLation in subjects with Psoriatic Arthritis (CONTROL)

Estudio fase 4 abierto randomizado controlado que COmpara la eficacia de la iNTROducción de adalimumab y el escaLado de dosis de metotrexato en pacientes con Artritis Psoriasica. (CONTROL)

A.3.1

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

A study of subjects with Psoriatic Arthritis to investigate the effectiveness of adalimumab introduction compared with methotrexate dose escalation

Es un estudio en pacientes con Artritis psoriásica para investigar la eficacia de la introducción de adalimumab comparado con el escalado de dosis de metotrexato.

A.4.1

Sponsor's protocol code number

M14-496

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	AbbVie Deutschland GmbH & Co. KG
B.1.3.4	Country	Germany
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	AbbVie Inc.
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	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	AbbVie House, Vanwall Business Park, Vanwall Road,
B.5.3.2	Town/ city	Maidenhead
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+34901 20 01 03
B.5.6	E-mail	abbvie_reec@abbvie.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	Humira 40mg/0.8ml solution for injection in pre-filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie 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	Adalimumab
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Adalimumab
D.3.9.1	CAS number	331731-18-1
D.3.9.2	Current sponsor code	Humira
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Metoject PEN 15 mg/0.30 ml solution for injection in pre-filled pen
D.2.1.1.2	Name of the Marketing Authorisation holder	medac GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Methotrexate
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Methotrexate
D.3.9.1	CAS number	59-05-2
D.3.9.3	Other descriptive name	METHOTREXATE
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
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	Metoject PEN 20 mg/0.40 ml solution for injection in pre-filled pen
D.2.1.1.2	Name of the Marketing Authorisation holder	medac GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Methotrexate
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Methotrexate
D.3.9.1	CAS number	59-05-2
D.3.9.3	Other descriptive name	METHOTREXATE
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
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: 4
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	Metoject PEN 25 mg/0.50 ml solution for injection in pre-filled pen
D.2.1.1.2	Name of the Marketing Authorisation holder	medac GmbH
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Methotrexate
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Methotrexate
D.3.9.1	CAS number	59-05-2
D.3.9.3	Other descriptive name	METHOTREXATE
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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: 5
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	MTX HEXAL 5 mg tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Hexal AG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Methotrexate
D.3.4	Pharmaceutical form	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	Methotrexate
D.3.9.1	CAS number	59-05-2
D.3.9.3	Other descriptive name	METHOTREXATE
D.3.9.4	EV Substance Code	SUB08856MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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

Psoriatic Arthritis

Artritis Psoriásica

E.1.1.1

Medical condition in easily understood language

Psoriatic Arthritis

Artritis Psoriásica

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	19.0
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 compare the effectiveness based on the achievement of minimal disease activity (MDA) at Week 16 between subjects who had adalimumab introduced and those that had methotrexate (MTX) escalated to the highest recommended dose of 20–25 mg every week (ew) or highest tolerable dose up to 25 mg ew after inadequate disease control on the initial MTX therapy.

Comparar la eficacia basada en el logro de una actividad mínima de la enfermedad ( AME) en semana 16 entre pacientes que recibieron adalimumab y aquellos que recibieron el escalado de dosis hasta la máxima recomendada de metotrexato (MTX) de 20-25mg semanalmente o la máxima tolerada hasta 25 mg semanalmente después de un control inadecuado de la enfermedad con la terapia inicial de MTX.

E.2.2

Secondary objectives of the trial

•To compare the effectiveness at Week 16 between subjects who had adalimumab introduced and those that had MTX escalated to the highest recommended dose of 20-25mg ew or highest tolerable up to 25mg ew based on following clinical, functional and quality of life measures:
-Psoriatic Arthritis Disease Activity Score (PASDAS)
-Disease Activity in Psoriatic Arthritis (DAPSA) score
-Psoriatic Arthritis Impact of Disease (PsAID) score
-American College of Rheumatology criteria (ACR)
-Disease Activity Score 28 (DAS28)
-Psoriasis Area and Severity Index (PASI)
-Health Assessment Questionnaire Disability Index (HAQ-DI)
-Short Form Health Survey 36 (SF-36) scores: total, physical component summary (PCS) and mental component summary (MCS)
-Dermatology Life Quality Index (DLQI)
-Leeds Enthesitis Index (LEI)
-Tender dactylitic digit count
•To evaluate the achievement of MDA at Week 32 on each of the four different treatment regimens involving adalimumab and/or MTX in Part 2 of the study

Protocolo Sección 4.2 Secondary Objective pág 29

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult male or female, ≥ 18 years of age
2. PsA diagnosis established at least 4 weeks prior to the date of the Screening visit and confirmed by C1ASsification of Psoriatic Arthritis (CASPAR) criteria at the Screening visit
3. Not in MDA at the time of screening, defined as not meeting at least 5 of the following 7 criteria:
• Tender joint count (TJC) ≤ 1 out of 68 assessed
• Swollen joint count (SJC) ≤ 1 out of 66 assessed
• PASI ≤ 1 or Body Surface Area (BSA) ≤ 3
• Patient's assessment of pain visual analogue scale (VAS) ≤ 15
• Patient's global assessment of disease activity (PtGA) VAS ≤ 20
• HAQ-DI score ≤ 0.5
• Tender entheseal points ≤ 1 out of 8 assessed
4. Has active arthritis defined as fulfilling both the below criteria:
• ≥ 3 tender joints (out of 68 assessed)
• ≥ 3 swollen joints (out of 66 assessed)
5. Treated with a stable dose of MTX 15 mg ew for PsA defined as:
• Oral or subcutaneous (sc) administration of MTX for at least 4 weeks and not more than 36 weeks (≥ 4 weeks and ≤ 36 weeks),
• Change of the MTX administration route (oral or sc) is permitted in this time period if the administered dose of MTX 15 mg ew is not changed,
• This is the first course of MTX the subject has been receiving for the treatment of PsA,
• Subject has not received a dosage of MTX higher than 15 mg ew prior to the screening visit
• Subject could have been receiving MTX doses lower than 15 mg ew before reaching the stable dose of MTX 15 mg ew defined above.
6. If subject is receiving concomitant oral corticosteroids, prednisone or equivalent must be ≤ 10 mg/day and the dose must be stable for at least 4 weeks prior to the Screening visit.
7. If subject is receiving nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX) 2 selective inhibitors, paracetamol (up to the maximum recommended dose in the local country label), or acetaminophen up to 3.0 grams/day, the dose must be stable for at least 2 weeks prior to the Screening Visit.
8. If subject is receiving other csDMARDs in addition to MTX (i.e., sulfasalazine or leflunomide), the dose must be stable for at least 4 weeks prior to the Screening visit. If csDMARDs are discontinued before study enrollment, the discontinuation must occur at least 4 weeks prior to the Screening Visit.

1.Varón o mujer adulto de 18 o más años de edad.
2. Diagnóstico de APs establecido como mínimo 4 semanas antes de la fecha de la visita de selección y confirmado utilizando los criterios de clasificación de la artritis psoriásica (CASPAR) en la visita de selección
3. 3. Ausencia de AME en el momento de la selección, definida como el incumplimiento de al menos 5 de los 7 criterios siguientes:
• Recuento de articulaciones dolorosas (RAD) ≤ 1 de las 68 evaluadas
• Recuento de articulaciones inflamadas (RAI) ≤ 1 de las 66 evaluadas
• PASI ≤ 1 o superficie corporal (SC) ≤ 3
• Evaluación del dolor realizada por el paciente con una escala analógica visual (EAV) ≤ 15
• Evaluación global de la actividad de la enfermedad realizada por el paciente (PtGA) con una EAV ≤ 20
• Puntuación HAQ-DI ≤ 0,5
• Puntos con entesitis dolorosa ≤ 1 de los 8 evaluados
4.Presencia de artritis activa definida como el cumplimiento de los dos criterios siguientes:
• ≥ 3 articulaciones dolorosas (de las 68 evaluadas)
• ≥ 3 articulaciones inflamadas (de las 66 evaluadas)
5. 5. Tratado con una dosis estable de MTX 15 mg por semana para la APs, definida como:
• Administración oral o subcutánea (sc) de MTX durante un mínimo de 4 semanas y un máximo de 36 semanas (≥ 4 semanas y ≤ 36 semanas).
• Durante ese período de tiempo se permitirá el cambio de la vía de administración de MTX (oral o sc) siempre que no cambie la dosis administrada de MTX 15 mg por semana.
• Este es el primer ciclo de MTX que el sujeto ha recibido para el tratamiento de la APs.
• El sujeto no ha recibido una dosis de MTX mayor de 15 mg por semana antes de la visita de selección.
• El sujeto puede haber recibido dosis de MTX menores de 15 mg por semana antes de alcanzar la dosis estable de MTX 15 mg por semana definida antes
6. Si el sujeto recibe tratamiento concomitante con corticosteroides orales, la dosis de prednisona o equivalente deberá ser ≤ 10 mg/día y deberá mantenerse estable durante un mínimo de 4 semanas antes de la visita de selección
7. Si el sujeto recibe antiinflamatorios no esteroideos (AINE), incluidos inhibidores selectivos de la ciclooxigenasa (COX)-2 o paracetamol (hasta la dosis máxima recomendada en la ficha técnica local o hasta 3,0 gramos/día), la dosis deberá mantenerse estable durante un mínimo de 2 semanas antes de la visita de selección.
8. Si el sujeto recibe otros FARMEsc además de MTX (p. ej., sulfasalazina o leflunomida), la dosis deberá mantenerse estable durante un mínimo de 4 semanas antes de la visita de selección. Si se interrumpe la administración de FARMEsc antes de la inclusión en el estudio, dicha interrupción tendrá que ocurrir un mínimo de 4 semanas antes de la visita de selección

E.4

Principal exclusion criteria

1. Has contraindication(s) to adalimumab therapy and/or known hypersensitivity to adalimumab or its excipients
2. Has history of MTX intolerance/toxicity
3. Has medical condition(s) precluding MTX dose increase above 15 mg ew
4. Has had prior exposure to any tumor necrosis factor (TNF) inhibitor, other mechanism of action biologic DMARD (bDMARD) or any systemic biologic agent in general

1. Contraindicaciones para recibir tratamiento con adalimumab o hipersensibilidad conocida al adalimumab o a sus excipientes.
2. Antecedentes de intolerancia o toxicidad del MTX.
3. Presencia de alguna condición médica que impida el aumento de la dosis de MTX por encima de 15 mg por semana.
4. Exposición previa a cualquier inhibidor del factor de necrosis tumoral (TNF), a otro FARME con un mecanismo de acción biológico (FARMEb) o a cualquier agente biológico sistémico en general

E.5 End points

E.5.1

Primary end point(s)

The proportion of subjects achieving MDA at Week 16 on adalimumab 40 mg eow plus MTX 15 mg ew as compared with subjects on MTX alone escalated to 20–25 mg or highest tolerable dose ew.

Proporción de sujetos con AME en la semana 16 con adalimumab 40 mg cada 2 semanas más MTX 15 mg por semana en comparación con los sujetos tratados con MTX en monoterapia con aumento de la dosis a 20-25 mg o a la dosis más alta tolerable por semana

E.5.1.1

Timepoint(s) of evaluation of this end point

16 weeks

Semana 16

E.5.2

Secondary end point(s)

● The following outcomes after 16 Weeks of treatment with adalimumab 40 mg eow plus MTX 15 mg ew compared with MTX alone escalated to 20-25 mg or highest tolerable dose ew:
- Change in PASDAS from baseline
- Change in DAPSA score from baseline
- Change in PsAID score from baseline
- Proportion of subjects achieving ACR 20/50/70 response
- Change in DAS28-CRP score from baseline
- Proportion of subjects achieving PASI 75/90/100 response among subjects with BSA ≥ 3%
- Change in HAQ-DI score from baseline
- Changes in total SF-36 score, PCS and MCS from baseline
- Change in DLQI score from baseline
- Change in Leeds Enthesitis Index (LEI) from baseline
- Change in tender dactylitic digit count from baseline
● The proportion of subjects in MDA at Week 32 on each of the four different treatment regimens (Arms 1-4) in Part 2 of the study

•Los resultados siguientes después de 16 semanas de tratamiento con adalimumab 40 mg cada 2 semanas más MTX 15 mg por semana en comparación con los sujetos tratados con MTX en monoterapia con aumento de la dosis a 20-25 mg o a la dosis más alta tolerable por semana:
o Variación de la puntuación PASDAS con respecto al momento basal
o Variación de la puntuación DAPSA con respecto al momento basal
o Variación de la puntuación PsAID con respecto al momento basal
o Proporción de sujetos que logran una respuesta ACR 20/50/70
o Variación de la puntuación DAS28-PCR con respecto al momento basal
o Proporción de sujetos que logran una respuesta PASI 75/90/100 entre los sujetos con una SC ≥ 3%.
o Variación de la puntuación HAQ-DI con respecto al momento basal
o Variación de la puntuación SF-36 total, PCS y MCS con respecto al momento basal
o Variación de la puntuación DLQI con respecto al momento basal
o Variación del Índice de entesitis de Leeds (LEI) con respecto al momento basal
o Variación del recuento de dedos con dactilitis dolorosa con respecto al momento basal
•Proporción de sujetos con AME en la semana 32 con cada una de las cuatro pautas diferentes de tratamiento (grupo 1-4) en la parte 2 del estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

16 week or 32 weeks depending on secondary endpoint

Semana 16 o 32 dependiendo del criterio de valoración secundario

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

Yes

E.6.10

Pharmacogenetic

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

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

Australia

Brazil

Canada

Colombia

European Union

Puerto Rico

Qatar

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 end-of-study is defined as the date of the last subject's last visit or the actual date of follow-up contact, whichever is later.

Se define como final del estudio la fecha de la última visita del último paciente o fecha real del contacto de seguimiento , lo que sea 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

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:

228

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

140

F.4.2.2

In the whole clinical trial

240

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)

Upon completion of the study, the subjects will be treated in accordance with the Investigator's best clinical judgement.

Una vez finalizado el estudio, los pacientes serán tratados conforme al mejor criterio clínico del investigador.

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

2017-02-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-21

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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