Clinical Trials Register

Summary
EudraCT Number:	2016-000933-37
Sponsor's Protocol Code Number:	M15-925
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-000933-37

A.3

Full title of the trial

A Phase 3, Randomized, Active-Controlled, Double Blind Study Comparing ABT-494 to Abatacept in Subjects with Moderately to Severely Active Rheumatoid Arthritis with Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs)

Sperimentazione di Fase 3, Randomizzata, in Doppio Cieco con Controllo Attivo per Confrontare ABT-494 rispetto ad Abatacept in Soggetti con Artrite Reumatoide in Fase Attiva e di Grado da Moderato a Severo, con Risposta Inadeguata o Intolleranza a Farmaci Antireumatici biologici Modificanti la Malattia (bDMARD) ed in Trattamento Stabile con Farmaci Antireumatici Sintetici Convenzionali Modificanti la Malattia (csDMARD)

A.3.1

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

Study to Compare ABT-494 to Abatacept in Subjects with Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who have an Inadequate Response or Intolerance to Biologic DMARDs (SELECT-CHOICE)

Sperimentazione per Confrontare ABT-494 rispetto ad Abatacept in Soggetti con Artrite Reumatoide in Trattamento Stabile con Farmaci Antireumatici Sintetici Convenzionali Modificanti la Malattia (csDMARD) che hanno una Risposta Inadeguata o Intolleranza a Farmaci biologici DMARDs (SELECT-CHOICE)

A.3.2

Name or abbreviated title of the trial where available

M15-925

A.4.1

Sponsor's protocol code number

M15-925

A.5.4

Other Identifiers

Name:

M15-925

Number:

M15-925

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	SL64UB
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441628561090
B.5.5	Fax number	00441628461153
B.5.6	E-mail	eu-clinical-trials@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	ABT-494
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	ABT-494
D.3.9.1	CAS number	1310726-60-3
D.3.9.2	Current sponsor code	ABT-494
D.3.9.3	Other descriptive name	ABT-494
D.3.9.4	EV Substance Code	SUB125895
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Orencia 250mg powder for concentrate for solution for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Abatacept
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABATACEPT
D.3.9.1	CAS number	332348-12-6
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB20635
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	250
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.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
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderately to Severely Active Rheumatoid Arthritis (RA)

Artrite Reumatoide in Fase Attiva e di Grado da Moderato a Severo

E.1.1.1

Medical condition in easily understood language

Rheumatoid Arthritis

Artrite reumatoide

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	23.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
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

1. To compare the safety and efficacy of ABT-494 versus abatacept intravenous (IV) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in bDMARD-inadequate response (bDMARD-IR) or bDMARD-intolerant subjects with moderately to severely active RA.
2. To evaluate the long-term safety, tolerability, and efficacy of ABT-494 in subjects with RA.

1. Confrontare la sicurezza e l’efficacia di ABT-494 rispetto ad abatacept per via endovenosa (EV) nel trattamento dei segni e sintomi dell’artrite reumatoide (AR) in soggetti con AR in fase attiva e di grado da moderato a severo con risposta inadeguata o intolleranza a un trattamento con bDMARD (rispettivamente bDMARD-inadequate response [bDMARD-IR] e bDMAR-intolerant).
2. Valutare la sicurezza, tollerabilità ed efficacia a lungo termine di ABT-494 nei soggetti con AR.

E.2.2

Secondary objectives of the trial

1. Change from baseline in DAS28 (CRP) at Week 12 (superiority).
2. Proportion of subject's achieving Clinical Remission (CR) at Week 12 (superiority).

1. Variazione rispetto al baseline del punteggio DAS28 (PCR) alla Settimana 12 (superiorità).
2. Proporzione di soggetti che raggiungono la remissione clinica (CR) alla settimana 12 (superiorità).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult male or female, at least 18 years old.
2. Diagnosis of RA for = 3 months.
3. Subjects have been treated for = 3 months with = 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration and have never received abatacept prior to the first dose of study drug.
4. Subjects have been receiving csDMARD therapy = 3 months and on a stable dose for = 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
5. Meets the following criteria: = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits and hsCRP = 3 mg/L at Screening.

1. Soggetti adulti di ambo i sessi di età pari o superiore a 18 anni.
2. Soggetti con diagnosi di AR da = 3 mesi.
3. Soggetti che hanno ricevuto trattamento per = 3 mesi con = 1 bDMARD ma che continuano a manifestare AR attiva oppure hanno dovuto interrompere il trattamento a causa di intolleranza o tossicità, a prescindere dalla durata del trattamento E che non hanno mai ricevuto abatacept prima della prima dose del medicinale sperimentale.
4. Soggetti che ricevono csDMARD da = 3 mesi con trattamento a dose stabile da = 4 settimane prima della prima dose del medicinale sperimentale. Sono permessi i seguenti csDMARD: MTX, sulfasalazina, idrossiclorochina, clorochina e leflunomide. È permessa la combinazione di un massimo di due csDMARD di background con l'eccezione della combinazione di MTX e leflunomide.
5. Soggetti che soddisfano entrambi i seguenti criteri di attività minima della malattia: tumefazione di = 6 articolazioni (su conta totale di 66 articolazioni) e dolorabilità alla palpazione di = 6 articolazioni (su conta totale di 68 articolazioni) alle visite di Screening e Baseline, e livelli di PCR ad alta sensibilità (hsCRP) = 3 mg/L alla Visita di Screening.

E.4

Principal exclusion criteria

1. Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
2. Prior exposure to abatacept
3. History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.

1. Pregressa esposizione a qualsiasi inibitore delle proteine Janus chinasi (JAK) (compresi, a titolo esemplificativo ma non esaustivo, tofacitinib, baricitinib e filgotinib).
2. Esposizione pregressa ad abatacept.
3. Storia di artropatia infiammatoria diversa da AR. Possono essere arruolati i soggetti con storia di Sindrome di Sjogren secondaria

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in DAS28 (CRP) (non-inferiority).

Variazione rispetto al baseline del punteggio DAS28 (CRP) (non-inferiorità).

E.5.1.1

Timepoint(s) of evaluation of this end point

week 12

settimana 12

E.5.2

Secondary end point(s)

1. Change from baseline in DAS28 (CRP) (superiority);
2. Proportion of subjects achieving Clinical Remission (CR) (superiority).

1. Vaeriazione rispetto al baseline del punteggio DAS 28 (CPR) (superiorità);
2. Proporzione di soggetti che raggiungono la remissione clinica (CR) (superiorità).

E.5.2.1

Timepoint(s) of evaluation of this end point

week 12

settimana 12

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

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)

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.3.1

Comparator description

Abatacept

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

Information not present in EudraCT

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

Belarus

Brazil

Canada

Chile

Colombia

Israel

Korea, Democratic People's Republic of

Korea, Republic of

Mexico

New Zealand

Puerto Rico

Russian Federation

Turkey

United States

Belgium

Bulgaria

France

Germany

Hungary

Ireland

Italy

Latvia

Netherlands

Norway

Poland

Portugal

Romania

Slovakia

Spain

Sweden

Switzerland

European Union

United Kingdom

Czechia

Argentina

Greece

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 or last follow up contact whichever is later

LVLS o o all'ultimo contatto di follow-up se posteriore

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:

413

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

137

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

237

F.4.2.2

In the whole clinical trial

313

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)

At the end of the study, subjects will be placed on standard of care per Investigator's clinical judgment in consultation with the study subject's physician. Subjects that prematurely discontinue from the study will be treated in accordance with the Investigator's clinical judgment.

Al termine della Sperimentazione, i soggetti verranno trattati secondo pratica clinica come da giudizio clinico del medico sperimentatore in accordo con il parere del medico che ha seguito il soggetto nel corso della sperimentazione. In caso di interruzione anticipata dalla sperimentazione i soggetti verranno trattati secondo parere clinico del medico sperimentatore.

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

2016-10-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-17

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

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