Clinical Trials Register

Summary
EudraCT Number:	2020-001690-72
Sponsor's Protocol Code Number:	M20-186
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:	2021-05-24
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-001690-72

A.3

Full title of the trial

A Phase 2, Long-Term Extension (LTE) Study with Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects with Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT)

Studio clinico di Fase 2 di Estensione a Lungo Termine (LTE) con Elsubrutinib e Upadacitinib somministrati da soli oppure in combinazione (ABBV-599) in soggetti affetti da Lupus Eritematoso Sistemico in fase attiva e di grado da moderato a grave che hanno completato lo studio clinico randomizzato e controllato (RCT) di Fase 2 M19-130

A.3.1

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

A Study to Investigate the Long-Term Safety and Efficacy of ABBV-599 (ABBV-105 and ABT-494 Given Alone or in Combination) in Participants with Moderately to Severely Active Systemic Lupus Erythematosus who have completed Study M19-130.

Studio clinico per studiare la sicurezza e l’efficacia a lungo termine di ABBV-599 (ABBV-105 e ABT-494 somministrati da soli oppure in combinazione) in partecipanti affetti da lupus eritematoso sistemico in fase attiva di grado da moderato a grave che hanno completato lo studio clinico M19-130

A.3.2

Name or abbreviated title of the trial where available

A Phase 2, Long-Term Extension (LTE) Study in Subjects with Moderately to Severely Active SLE

Uno studio di fase 2, estensione a lungo termine (LTE) in soggetti con LES da moderato a gravemente

A.4.1

Sponsor's protocol code number

M20-186

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, Vanwell 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	441628561090
B.5.5	Fax number	441628461153
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	Elsubrutinib
D.3.2	Product code	[ABBV-105]
D.3.4	Pharmaceutical form	Capsule
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	Elsubrutinib
D.3.9.1	CAS number	1643570-24-4
D.3.9.2	Current sponsor code	ABBV-105
D.3.9.4	EV Substance Code	SUB192702
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	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	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	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	2050057-56-0
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	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	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	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	2050057-56-0
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	29
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	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	Capsule
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Systemic Lupus Erythematosus (SLE)

E.1.1.1.IT - Condizione clinica in un linguaggio facilmente comprensibile
Il lupus eritematoso sistemico (LES) è una patologia cronica in cui il sistema immunitario dell’organismo può attaccare la pelle, le articolazioni, i reni, il cervello e/o altri organi dell’organismo stesso. Spesso colpisce con maggiore frequenza le donne e le persone di origine africana.

Lupus eritematoso sistemico (LES)

E.1.1.1

Medical condition in easily understood language

SLE is a chronic disease where the body's immune system may attack the body's own skin, joints, kidneys, brain, and/or other organs. Women and people of African descent are more often affected.

[campi non sufficienti - vedere sezione E.1.1.EN]

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

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	10042945
E.1.2	Term	Systemic lupus erythematosus
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 long-term safety and tolerability of elsubrutinib and upadacitinib given alone or as the ABBV-599 (elsubrutinib/upadacitinib) combination in SLE subjects who have completed the M19-130 Phase 2 study.

Valutare la sicurezza e tollerabilità a lungo termine di elsubrutinib e upadacitinib somministrati da soli oppure nella forma della combinazione ABBV-599 (elsubrutinib/upadacitinib) in soggetti affetti da LES che hanno completato lo studio di Fase 2 M19-130

E.2.2

Secondary objectives of the trial

To obtain longer-term efficacy data beyond Week 48 with the treatments studied in the RCT (monotherapies and combination) to more fully assess the risk/benefit of each treatment over time.

Ottenere dati di efficacia più a lungo termine oltre la Settimana 48 per i trattamenti studiati nell’ambito dello studio clinico randomizzato controllato (RCT) (monoterapie e terapia combinata) per valutare in maniera più approfondita nel tempo il profilo rischi/benefici di ciascun trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects will have completed Study M19-130 (i.e., the preceding study of elsubrutinib, upadacitinib, and ABBV599 [elsubrutinib/upadacitinib] combination)
2. Subjects must be on stable background treatment for SLE throughout the study.
3. Subjects must understand and voluntarily sign and date an IEC/IRB- approved informed consent
4. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test
5. Female subjects must be either postmenopausal, OR permanently surgically sterile OR practicing at least one protocol-specified method of birth control

1. Soggetti che hanno completato lo Studio M19-130 (ovvero lo studio pregresso su elsubrutinib, upadacitinib e la combinazione ABBV-599 [elsubrutinib/upadacitinib]).
2. I soggetti devono essere in trattamento background per LES a dose stabile per l’intera durata dello studio clinico.
3. I soggetti devono comprendere e volontariamente firmare e datare un consenso informato approvato dal comitato etico.
4. Le donne in età fertile devono avere un risultato negativo all’test di gravidanza su urine.
5. i soggetti di sesso femminile devono essere in menopausa OPPURE sterili in maniera permanente dopo intervento chirurgico OPPURE devono utilizzare almeno un metodo contraccettivo fra quelli specificati dal protocollo.

E.4

Principal exclusion criteria

1. Subjects may not have any active, chronic, or recurrent viral or bacterial infection.
2. Must not require vaccination with any live vaccine during study participation.
3. Must not have a history of any malignancy except for successfully treated Non-Melanoma Skin Cancer (NMSC) or localized carcinoma in-situ (CIS) of the cervix.
4. Must not be a recipient of an organ transplant.
5. Women must not be pregnant, breastfeeding, or considering becoming pregnant during the study and for at least 30 days after the last dose of study drug.

1. I soggetti non devono presentare infezione virale o batterica attiva, cronica o ricorrente.
2. I soggetti non devono necessitare di vaccinazione con qualsiasi vaccino vivo nel corso della partecipazione allo studio.
3. I soggetti non devono avere una storia di neoplasia maligna di qualsiasi tipo, ad eccezione del carcinoma cutaneo non melanoma (NMSC) oppure carcinoma localizzato in situ (CIS) della cervice uterina trattati con successo.
4. I soggetti non devono aver ricevuto un trapianto d’organo.
5. Le donne non devono essere in stato di gravidanza, non devono allattare al seno o programmare una gravidanza durante lo studio clinico e per almeno 30 giorni dopo l’ultima dose del medicinale sperimentale.

E.5 End points

E.5.1

Primary end point(s)

Not applicable.

Non applicabile

E.5.1.1

Timepoint(s) of evaluation of this end point

Not applicable.

Non applicabile

E.5.2

Secondary end point(s)

• SLE Responder Index (SRI)-4.
• British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA).
• Steroid burden, assessed as change from M19-130 Baseline.
• Number of mild, moderate or severe flares per patient-year (respectively and overall) by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI flare index (SFI), assessed by number and types of flare per subject compared across treatment groups .

• Punteggio SRI-4 (SLE Responder Index)
• Punteggio dell’indice BICLA (BILAG [British Isles Lupus Assessment Group] Based Combined Lupus Assessment)
• Burden del trattamento con steroidi, valutato sulla base della variazione rispetto al baseline dello studio M19-130
• Numero di esacerbazioni lievi, moderate o gravi per anno-paziente (rispettivamente per ciascuna gravità e globalmente) in base al punteggio dell’indice relativo alle esacerbazioni (SFI) SLEDAI modificato sulla base dello studio SELENA (Safety of Estrogens in Lupus Erythematosus National Assessment), valutato in base al numero e ai tipi di esacerbazione per soggetto, confrontato fra i diversi gruppi di trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

All visits.

Tutte le visite

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

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

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

Canada

China

Colombia

Japan

Korea, Republic of

Mexico

Taiwan

United States

France

Germany

Hungary

Italy

Netherlands

Poland

Spain

United Kingdom

Argentina

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 date of the last follow-up contact, whichever is later.

Per conclusione dello studio si intende la data dell’ultima visita dell’ultimo soggetto, oppure la data dell’ultimo contatto di follow-up, quale dei due avvenga per ultimo

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:

260

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Those that cannot consent on their own to the study for certain purposes per local regulations. The legally authorized representative would fulfill all statutory requirements for the patient.

Quelli che non possono acconsentire da soli allo studio per determinati scopi secondo le norme locali. Il rappresentante legalmente autorizzato soddisferebbe tutti i requisiti di legge per il paziente.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

260

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)

AbbVie does not plan to offer any additional therapies after the subject's last study visit or discontinuation of study drug.

AbbVie non intende offrire ai soggetti alcuna terapia aggiuntiva dopo la loro ultima visita per lo studio o dopo l’interruzione del medicinale sperimentale

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

2020-10-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-22

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

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