Clinical Trials Register

Summary
EudraCT Number:	2018-003987-29
Sponsor's Protocol Code Number:	APD334-303
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-08-22
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

Netherlands - Competent Authority

A.2

EudraCT number

2018-003987-29

A.3

Full title of the trial

An Open-Label Extension Study of Etrasimod in Subjects with Moderately to Severely Active Ulcerative Colitis

A.3.1

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

An Open-Label Extension Study for Treatment of Moderately to Severely Active Ulcerative Colitis

A.3.2

Name or abbreviated title of the trial where available

ELEVATE UC OLE

A.4.1

Sponsor's protocol code number

APD334-303

A.5.4

Other Identifiers

Name:

IND number

Number:

125154

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	Arena Pharmaceuticals Inc.
B.1.3.4	Country	United States
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	Arena Pharmaceuticals 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	Arena Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Giles Hulley
B.5.3	Address:
B.5.3.1	Street Address	6154 Nancy Ridge Drive
B.5.3.2	Town/ city	San Diego - CA
B.5.3.3	Post code	92121
B.5.3.4	Country	United States
B.5.4	Telephone number	0018582104528
B.5.6	E-mail	ghulley@arenapharm.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	Etrasimod
D.3.2	Product code	APD334
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	etrasimod L-arginine
D.3.9.1	CAS number	1206123-97-8
D.3.9.2	Current sponsor code	APD334 L-arginine
D.3.9.3	Other descriptive name	AR401959 L-arginine
D.3.9.4	EV Substance Code	SUB171412
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	2
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

Ulcerative Colitis

E.1.1.1

Medical condition in easily understood language

Ulcerative Colitis a form of inflammatory bowel disease.

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045366
E.1.2	Term	Ulcerative colitis, unspecified
E.1.2	System Organ Class	100000004856

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 assess the safety of long-term administration of etrasimod in subjects with moderately to severely active ulcerative colitis (UC)

E.2.2

Secondary objectives of the trial

To assess the long-term efficacy of etrasimod in subjects with moderately to severely active UC

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Must have met the eligibility criteria and have been enrolled in one of the two parent studies (APD334-301 or APD334-302) and also meet the following additional criteria:
a. Subjects previously enrolled in Study APD334-301 must have either:
I. Completed the Week 12 visit and have been assessed to have active UC that had deteriorated from baseline and meet one of the following criteria:
• Absolute RB ≥ 2 on 2-consecutive days, and confirmation of ES ≥ 2 at or after the Week 12 assessment
• Absolute RB + SF ≥ 4 on 2-consecutive days, and confirmation of ES ≥ 2 at or after the Week 12 assessment
• Absolute RB ≥ 2 or RB + SF ≥ 4 (in any order) on 2-consecutive days, and confirmation of ES ≥ 2 at or after the Week 12 assessment
or
II. Completed the Week 52 visit
Note: An endoscopic evaluation is required, however a proctosigmoidoscopy does not need to be repeated if performed within the last 4 weeks
b. Subjects previously enrolled in APD334-302 must have completed the Week 12 visit
2. Eligible women of childbearing potential must fulfill the following:
a. Have a negative urine beta human chorionic gonadotropin (β-hCG) pregnancy test
b. Not breastfeeding
3. Both men and women subjects agree to use a highly effective method of birth control throughout the entire study period, from informed consent through the adverse event reporting period (30 days after the last dose of study treatment), if the possibility of conception exists. Eligible men and women subjects must also agree not to participate in a conception process (ie, actively attempt to become pregnant or to impregnate, sperm
donation, in vitro fertilization) during the study and for 30 days after the last dose of study treatment. Highly effective birth control methods include the following
• Oral, implantable, or injectable contraceptives (starting ≥ 60 days before dosing) in combination with a diaphragm with vaginal spermicide, cervical cap with vaginal spermicide, or male condom; hormonal contraceptives (subjects should be consistently taking the hormonal contraceptive for at least 3 months [90 days] prior to the Eligibility assessment)
• Standard intrauterine device (IUD; eg, Copper T 380A IUD), intrauterine system (IUS; eg, LNg 20 IUS - progesterone IUD), progesterone implant, or tubal sterilization (≥ 180 days after surgery)
• Vasectomized male subjects using a condom, partner using diaphragm with spermicide, cervical cap with spermicide, estrogen and progesterone oral contraceptives (“the pill”), estrogen and progesterone transdermal patch, vaginal ring, or progesterone injection
• Complete sexual abstinence defined as refraining from heterosexual intercourse for the entire period of risk associated with study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable
Note: Women who are surgically sterile or postmenopausal (defined as: 12 consecutive months with no menses without an alternative medical cause) are not considered to be of childbearing potential. If of childbearing potential, female partners of participating male subjects should agree to utilize a highly effective method of contraception for the duration of study participation.
4. Ability to provide written informed consent or assent (parent or legal guardian must provide consent for a subject < 18 years of age or as required per local regulations who has assented to participate in the study) and to be compliant with the schedule of protocol assessments

E.4

Principal exclusion criteria

Subjects who meet ANY of the following exclusion criteria will NOT be eligible for enrollment into the study:
1. If the Investigator considers the subject to be unsuitable for any reason to participate in the OLE study

Exclusions related to general health:
2. Experienced an adverse event that led to discontinuation from parent etrasimod study
3. Day 1 pre-dose sitting vital sign assessment: heart rate < 50 bpm and systolic BP < 90 mm Hg
4. Day 1 pre-dose 12-lead electrocardiogram (ECG) in the supine position showing a second or third-degree AV block, periods of asystole > 3 seconds, PR interval > 200 ms, or QTcF ≥ 450 ms (males) or QTcF ≥ 470 ms (females)
5. Subjects requiring colectomy during the parent study
6. Subjects requiring treatment with prohibited medications as defined in the parent study

Exclusions related to laboratory results:
7. Laboratory values that meet study treatment discontinuation rules
Note: In the case of any abnormal laboratory results, laboratory tests may be repeated once and if these results are within normal range, the subject is eligible for enrollment.

E.5 End points

E.5.1

Primary end point(s)

• Incidence of treatment-emergent adverse events and serious adverse events (SAEs)
• Incidence and severity of laboratory abnormalities, and change from baseline in laboratory values (hematology, serum chemistry, coagulation, and urinalysis)
• Incidence of vital sign abnormalities and changes from baseline

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 2, 4, 8, 12, 24, 36, 52, 64, 76, 88, 104, 116, 128, 140, 156, 168, 180, 192, 2018, 220, 232, 244, 260, 2 week Follow-up visit

E.5.2

Secondary end point(s)

• Proportion of subjects achieving clinical remission at each of the following weeks: Weeks 52, 104, 156, 208, and 260
• Proportion of subjects achieving clinical response at each of the following weeks: Weeks 52, 104, 156, 208, and 260
• Proportion of subjects achieving symptomatic remission at Weeks 52, 104, 156, 208, and 260
• Proportion of subjects achieving non-invasive response at each of the following weeks: Weeks 12, 24, 36, 52, 104, 156, 208, and 260
• Proportion of subjects remaining in clinical remission at the following weeks: Weeks 12, 52, 104, 156, 208, and 260
• Longitudinal change from both OLE and parent study baseline in SF, RB, and SF + RB at each of the following weeks: Weeks 12, 24, 36, 52, 104, 156, 208, and 260
• Proportion of subjects with remission and response using total Mayo Clinic score at each of Weeks 12, 52, and annually thereafter up to Week 260
• Histologic improvement at each visit with endoscopy
• Histologic remission at each visit with endoscopy
• Time to loss of response, with loss of response defined by:
− A ≥ 2-point increase from Week 12 in the combined SF + RB scores and combined SF + RB score of ≥ 4, on 2 consecutive visits (≥ 7 days apart), and
− Confirmed by centrally read ES ≥ 2 and,
− Confirmation of negative C. difficile testing
• Proportion of subjects with improvement in EIMs at Weeks 12, 52, 104, 156, 208, and 260, in subjects with EIMs at baseline.

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 12, 24, 36, 52, 104, 156, 208, and 260

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

253

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

Austria

Belarus

Belgium

Brazil

Bulgaria

Canada

Chile

China

Colombia

Croatia

Czech Republic

Denmark

Egypt

Estonia

France

Georgia

Germany

Hungary

India

Israel

Italy

Japan

Korea, Republic of

Latvia

Lebanon

Lithuania

Mexico

Moldova, Republic of

Netherlands

Poland

Portugal

Romania

Russian Federation

Serbia

Slovakia

South Africa

Spain

Switzerland

Taiwan

Thailand

Turkey

Ukraine

United Kingdom

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

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

Yes

F.1.1