Clinical Trials Register

Summary
EudraCT Number:	2019-003229-12
Sponsor's Protocol Code Number:	M19-944
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:	2020-03-06
Trial 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

2019-003229-12

A.3

Full title of the trial

A Phase 3 Randomized, Placebo-Controlled, Double-Blind Program to Evaluate Efficacy and Safety of Upadacitinib in Adult Subjects with Axial Spondyloarthritis

Programa de fase 3 aleatorizado, controlado con placebo y doble ciego para evaluar la eficacia y la seguridad de upadacitinib en pacientes adultos con espondiloartritis axial

A.3.1

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

Evaluation of upadacitinib in adult subjects with axial spondyloarthritis

Evaluación del upadacitinib en sujetos adultos con espondiloartritis axial

A.4.1

Sponsor's protocol code number

M19-944

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, Berkshire
B.5.3.3	Post code	SL6 4UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0044901200103
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	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	Upadacitinib
D.3.2	Product code	ABT-494
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	UPADACITINIB
D.3.9.1	CAS number	1310726-60-3
D.3.9.2	Current sponsor code	ABT-494
D.3.9.4	EV Substance Code	SUB187251
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	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	Yes
D.3.11.13.1	Other medicinal product type	Janus kinase (JAK) 1 inhibitor

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	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

Axial Spondyloarthritis

Espondiloartritis axial

E.1.1.1

Medical condition in easily understood language

Axial Spondyloarthritis

Espondiloartritis axial

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10071400
E.1.2	Term	Axial spondyloarthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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	10076297
E.1.2	Term	Non-radiographic axial spondyloarthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10002556
E.1.2	Term	Ankylosing spondylitis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective 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

• To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adult subjects with active axSpA including AS who had an inadequate response to a biologic disease-modifying antirheumatic drug (bDMARD) therapy (Study 1) and nr axSpA (Study 2);
• To assess the safety and tolerability of upadacitinib in subjects with active axSpA including bDMARD-IR AS (Study 1) and with nr axSpA (Study 2).

- Para evaluar la eficacia del upacitinib se comparará con placebo la reducción de signos y síntomas en sujetos adultos con axSpa incluyendo AS quien ha tenido una inadecuada respuesta a terapia biológica antirreumática modificadora de la enfermedad (bDMARD) (Estudio 1) y nr-axSpA (Estudio 2).
- Evaluar la seguridad y tolerabilidad del upadacitinib en sujetos con axSpA activo, incluido bDMARD-IR AS (Estudio 1) y con nr-axSpA (Estudio 2).

E.2.2

Secondary objectives of the trial

• To evaluate the safety and tolerability of upadacitinib in extended treatment in adult subjects with active axSpA including bDMARD-IR AS who have completed the Double Blind Period (Study 1) and with nr-axSpA who have completed the Double Blind Period (Study 2).

- Para evaluar la seguridad y tolerabilidad a upacitinib en tratamiento prolongado en sujetos adultos con axSpA activo, incluyendo bDMARD-IR AS que han completado el Período Doble Ciego (Estudio 1) y con nr-axSpA que han completado el Período Doble Ciego (Estudio 2).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• adult females and males who are at least 18 years of age
• clinical diagnosis of AS who meet the modified New York Criteria for AS (Study 1); OR
• clinical diagnosis of nr-axSpA fulfilling the 2009 ASAS classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS and have objective signs of active inflammation on MRI of sacroiliac joints or based on high sensitivity CRP > ULN (Study 2).
• must have a BASDAI score ≥ 4 and a Patient's Assessment of Total Back Pain score ≥ 4 based on a 0 – 10 numerical rating scale at the Screening and Baseline Visits.
• For Study 1, subjects must have discontinued 1 bDMARD (either 1 tumor necrosis factor (TNF) inhibitor or 1 interleukin [IL]-17 inhibitor) due to either intolerance or lack of efficacy.
• For Study 2, prior treatment with at most 1 bDMARD (either 1 TNF inhibitor or 1 IL-17 inhibitor) is allowed in at least 25%, but not exceeding 35% of subjects

- Los adultos de ambos sexos que tengan al menos 18 años de edad
- Diagnóstico clínico de EA que cumplen con los Criterios de Nueva York modificados para
AS (Estudio 1); O
- Diagnóstico clínico de nr-axSpA que cumple los criterios de clasificación ASAS 2009 para axSpA pero que no cumple el criterio radiológico de los criterios modificados de Nueva York para AS y tiene signos objetivos de inflamación activa en la IRM de las articulaciones sacroilíacas o basados en la CRP de alta sensibilidad > ULN (Estudio 2).
- Debe tener un puntaje de BASDAI ≥ 4 y un puntaje de Evaluación del Dolor Total de Espalda del Paciente ≥ 4 basado en una escala numérica de calificación de 0 - 10 en las Visitas de Revisión y visita basal.
- Para el Estudio 1, los sujetos deben haber descontinuado 1 bDMARD (ya sea 1 inhibidor del factor de necrosis tumoral (TNF) o 1 inhibidor de interleucina[IL]-17) debido a intolerancia o falta de eficacia.
- Para el Estudio 2, se permite el tratamiento previo con un máximo de 1 bDMARD (1 inhibidor del TNF o 1 inhibidor de la IL-17) en al menos el 25%, pero sin exceder el 35% de los sujetos.

E.4

Principal exclusion criteria

• Subject must not have total spinal ankylosis
• Subjects who have had an inadequate response to both a TNF inhibitor and IL-17 inhibitor are not eligible.

- Los sujetos no deben tener la médula espinal totalmente anquilosada
- Los sujetos quienes hayan tenido una respuesta inadecuada a los inhibidores TNf y a los inhibidores del IL-17 no son elegibles.

E.5 End points

E.5.1

Primary end point(s)

Study 1 - proportion of subjects achieving an ASAS 40 response
Study 2 - proportion of subjects achieving an ASAS 40 response

Estudio 1- proporción de sujetos que han desarrollado una respuesta de 40 ASAS
Estudio 2- proporción de sujetos que han desarrollado una respuesta de 40 ASAS

E.5.1.1

Timepoint(s) of evaluation of this end point

Study 1 - Week 14
Study 2 - Week 14 (EU/EMA regulatory purposes); Week 52 (US/FDA regulatory purposes).

Estudio 1 - Semana 14
Estudio 2 - Semana 14 (Fines regulatorios de UE / EMA ); Semana 52 (Fines regulatorios de EE.UU/ FDA).

E.5.2

Secondary end point(s)

Study 1:
1. Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS);
2. Change from Baseline in magnetic resonance imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) score (spine);
3. Proportion of subjects with ASAS partial remission (PR) (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS 40);
4. Proportion of subjects with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response;
5. Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI);
6. Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL);
7. Change from Baseline in ASAS Health Index (HI);
8. Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES);
9. Change from Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin).

Study 2:
1. Change from Baseline in ASDAS;
2. Change from Baseline in MRI SPARCC score (SI joints);
3. Proportion of subjects with BASDAI 50 response;
4. Proportion of subjects with ASAS PR (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS 40);
5. Change from Baseline in BASFI;
6. Change from Baseline in ASQoL;
7. Change from Baseline in ASAS HI;
8. Change from Baseline in MASES;
9. Change from Baseline in BASMIlin.

Estudio 1.
Cambio desde la visita basal en la puntuación de actividad de la espondilitis anquilosante
(ASDAS);
2. Cambio con respecto a la visita basal en imágenes por resonancia magnética (IRM)
Puntaje del Spondyloarthritis Research Consortium of Canada (SPARCC) (columna vertebral);
3. Proporción de sujetos con remisión parcial (RP) de la ASAS (en términos absolutos) de ≤ 2 unidades para cada uno de los 4 dominios identificados en ASAS 40);
4. Proporción de sujetos con espondilitis anquilosante de baño Índice de actividad (BASDAI) 50 respuestas;
5. Cambio desde la visita basal en el índice funcional de la espondilitis anquilosante en el Índice funcional de la espondilitis anquilosante de baño (BASFI);
6. Cambio desde la visita basal en la calidad de vida de la espondilitis anquilosante
(ASQoL);
7. Variación con respecto a la visita basal del Índice de Salud ASAS (HI);
8. Cambio con respecto a la visita basal en la entesitis por espondilitis anquilosante de Maastricht Puntuación (MASES);
9. Cambio desde la visita basal en la metrología de la espondilitis anquilosante en baño lineal
Índice (BASMIlin).

Estudio 2.
1. Cambio desde la visita basal en ASDAS;
2. Cambio desde la visita basal en la puntuación de MRI SPARCC (articulaciones SI);
3. Proporción de sujetos con respuesta BASDAI 50;
4. Proporción de sujetos con ASAS PR (una puntuación absoluta de ≤ 2 unidades para cada uno de los 4 dominios identificados en ASAS 40);
5. Cambio desde la visita basal en BASFI;
6. Cambio desde la visita basal en ASQoL;
7. Cambio desde la visita basal en ASAS HI;
8. Cambio desde la visita basal en MASES;
9. Cambio desde la visita basal en BASMIlin.

E.5.2.1

Timepoint(s) of evaluation of this end point

Study 1 and Study 2 - Week 14

Estudio 1 y Estudio 2 - Semana 14

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Argentina

Australia

Brazil

Canada

China

Japan

Korea, Republic of

Mexico

New Zealand

Russian Federation

Taiwan

Turkey

Ukraine

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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:

630

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

300

F.4.2.2

In the whole clinical trial

690

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)

Subjects will be expected to go on standard of care after study completion.

Se espera que los sujetos continúen con el mismo nivel de cuidado después de terminar sus estudios.

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

2020-03-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-14

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

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