Clinical Trials Register

Summary
EudraCT Number:	2017-001225-41
Sponsor's Protocol Code Number:	M14-430
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-03-06
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

Slovenia - JAZMP

A.2

EudraCT number

2017-001225-41

A.3

Full title of the trial

A Multicenter, Randomized, Double-Blind, Placebo- Controlled Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Crohn's Disease who Completed the Studies M14-431 or M14-433

Multicentrična, randomizirana, dvojno slepa, s placebom kontrolirana študija vzdrževalnega zdravljenja in dolgoročno podaljšanje študije za oceno učinkovitosti in varnosti upadacitiniba (ABT-494) pri preiskovancih s Crohnovo boleznijo, ki so zaključili sodelovanje v študijah M14-431 ali M14-433

A.3.1

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

A Maintenance and Long-Term Extension Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Crohn's Disease who Completed the Studies M14-431 or M14-433

Študija vzdrževalnega zdravljenja in dolgoročno podaljšanje študije za oceno učinkovitosti in varnosti upadacitiniba (ABT-494) pri preiskovancih s Crohnovo boleznijo, ki so zaključili sodelovanje v študijah M14-431 ali M14-433

A.4.1

Sponsor's protocol code number

M14-430

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	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	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.3.9.3	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	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.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	1310726-60-3
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	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	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

Crohn's Disease (CD)

Crohnova bolezen

E.1.1.1

Medical condition in easily understood language

CD is an inflamatory bowel disease affects the lining of the digestive tract, often spreads into the layers of affected bowel tissue, can lead to abdominal pain, severe diarrhea, fatigue, weight loss.

CD je vnetna črevesna bolezen, ki prizadene sluznico prebavnega trakta, pogosto se razširi v plasti prizadetega črevesnega tkiva, lahko povzroči bolečine v trebuhu, hudo drisko, utrujenost, hujšanje.

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

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	10011401
E.1.2	Term	Crohn's disease
E.1.2	System Organ Class	10017947 - Gastrointestinal 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

Substudy 1 (randomized, double-blind, placebo-controlled maintenance): To evaluate the efficacy and safety of two doses of upadacitinib versus placebo as maintenance therapy in subjects with moderately to severely active Crohn's disease (CD) who responded to upadacitinib induction treatment in Studies M14-431 or M14-433.
Substudy 2 (long-term extension [LTE]): To evaluate safety and efficacy of long-term administration of upadacitinib in subjects with moderately to severely active CD who participated in the Phase 3 upadacitinib induction and maintenance studies.

Podštudija 1 (randomizirano, dvojno slepo, s placebom kontrolirano vzdrževalno zdravljenje): oceniti učinkovitost in varnost dveh višin odmerkov upadacitiniba v primerjavi s placebom kot vzdrževalnega zdravljenja pri preiskovancih z zmerno do zelo aktivno Crohnovo boleznijo, pri katerih je prišlo do odziva na indukcijsko zdravljenje z upadacitinibom v študijah M14-431 oziroma M14-433.
Podštudija 2 (dolgoročno podaljšanje): oceniti varnost in učinkovitost dolgotrajnega odmerjanja upadacitiniba pri preiskovancih, ki imajo zmerno do zelo aktivno Crohnovo bolezen in so sodelovali v študijah faze 3 z indukcijskim ali vzdrževalnim zdravljenjem z upadacitinibom.

E.2.2

Secondary objectives of the trial

To evaluate improvements in several efficacy parameters, including steroid discontinuation, laboratory parameters and quality of life questionnaires.

Za ovrednotenje izboljšav pri več parametrih učinkovitosti, vključno s prekinitvijo zdravljenja s steroidi, laboratorijskimi parametri in vprašalniki o kakovosti življenja.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Substudy 1 - 52-Week, Randomized, Double-Blind, Maintenance
Substudy 2 - 240-Week Long-Term-Extension

Podštudija 1 -52 tedensko randomizirano dvojno slepo vzdrževalno zdravljenje
Podštudija 2 -240 tedensko dolgoročno podaljšanje

E.3

Principal inclusion criteria

For Substudy 1:
- Subject who receive double-blind treatment in Study M14- 431 or Study M14-433 and achieve clinical response.
- Subject completes Week 12 or Week 24 study procedures in study M13-431 or study M14-433. The final endoscopy for studies M14-431 or M14-433 may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic.
For Substudy 2:
- Subject completes Substudy 1 of Study M14-430. The week 52 endoscopy may be missing, if the endoscopy cannot be performed during the coronavirus SARS-CoV-2 pandemic.
- Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431.

E.4

Principal exclusion criteria

For Sub-studies 1 and 2:
- Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
- Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an adverse event during Study M14-431, M14-433, or Substudy 1 of Study M14-430 that in the investigator's judgment makes the subject unsuitable for this study.
- Subject with any active or chronic recurring infections based on the investigator's assessment that makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed and the infection is resolved, based on the investigator's assessment.
- Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Study M14-431 (Week 24) or Substudy 1 of Study M14-430 (Week 40).

E.5 End points

E.5.1

Primary end point(s)

Substudy 1, Cohort 1 (Upadacitinib vs Placebo)
Co-Primary Endpoints:
 Proportion of subjects with clinical remission per PRO at Week 52, AND
 Proportion of subjects with endoscopic response at Week 52

Substudy 2
Primary Endpoint: Incidence of AEs over time

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 52

Teden 52

E.5.2

Secondary end point(s)

Substudy 1
1. Proportion of subjects with clinical remission per CDAI at Week 52
2. Proportion of subjects with endoscopic remission at Week 52
3. Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 52
4. Proportion of subjects achieving CR-100 at Week 52
5. Proportion of subjects who discontinued corticosteroid use for CD at least 90 days prior to Week 52 and achieved clinical remission per PROs at Week 52 in subjects taking corticosteroids for CD at Baseline of induction
6. Proportion of subjects with clinical remission per PROs at Week 0 and Week 52
7. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52
8. Proportion of subjects with clinical remission per PROs and endoscopic remission and Week 52
9. Proportion of subjects with CD-related hospitalizations during the 52-Week double-blind maintenance period.
10. Proportion of subjects with resolution of extra-intestinal manifestation (EIM) at Week 52, in subjects with EIMs at Baseline.

Substudy 2
Proportion of subjects
 with clinical remission over time
 with enhanced clinical response over time
 with endoscopic remission at Week 0, and every 48 weeks thereafter
 with endoscopic response at Week 0, and every 48 weeks thereafter
 who discontinue corticosteroid use and achieve clinical remission over time among subjects taking steroids at Baseline (of induction)
 with clinical remission over time who were in clinical remission at Week 0
 achieving Inflammatory Bowel Disease Questionnaire (IBDQ) response (increase of IBDQ ≥ 16 over time)
Time loss of
 enhanced clinical response
 clinical remission

E.5.2.1

Timepoint(s) of evaluation of this end point

Substudy 1
1. week 52
2. week 52
3. week 52
4. week 52
5. week 52
6. week 52
7. week 52
8. week 52
9. week 52
10. week 52
11. week 52
12. week 52
13. week 52
Substudy 2
Over study duration

Podštudija 1
1. teden 52
2. teden 52
3. teden 52
4. teden 52
5. teden 52
6. teden 52
7. teden 52
8. teden 52
9. teden 52
10. teden 52
11. teden 52
12. teden 52
13. teden 52
Podštudija 2
Čez čas trajanja študije

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

Yes

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Podštudija 1 Randomizirana, dvojno slepa. Podštudija 2 Odprta in dvojno slepa

Substudy 1 Randomized, double-blind. Substudy 2 Both open-label and double-blind

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

146

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

Belarus

Bosnia and Herzegovina

Brazil

Canada

Chile

China

Colombia

Egypt

Hong Kong

Israel

Japan

Korea, Republic of

Malaysia

Mexico

New Zealand

Puerto Rico

Russian Federation

Serbia

Singapore

South Africa

Switzerland

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:

710

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

457

F.4.2.2

In the whole clinical trial

738

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 study will be active until upadacitinib is approved. Subject may continue to receive upadacitinib once available in the approved country, or have the treatment change to standard of care, per the investigatory decision.

Študija bo aktivna, dokler ne bo odobren upadacitinib. Subjekt lahko še naprej prejema upadacitinib, ko bo na voljo v odobreni državi, ali pa bodo prejemali zdravljenje v okviru standarda oskrbe po presoji raziskovalca.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-02

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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