Clinical Trials Register

Summary
EudraCT Number:	2018-003987-29
Sponsor's Protocol Code Number:	APD334-303
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-10-23
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

Bulgarian Drug Agency

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.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03950232

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 Development GmbH
B.5.2	Functional name of contact point	Christophe Dubreuil
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017-5755
B.5.3.4	Country	United States
B.5.4	Telephone number	+4141 5620528
B.5.6	E-mail	Christophe.Dubreuil@pfizer.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 PF-07915503-94 (L-arginine salt)
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 the qualified Phase 2 and 3 parent studies listed below or other qualified region-specific studies and meet the following additional criteria:
a. Subjects previously enrolled in Study APD334-301 or APD334-210 must have either:
I. Completed the Week 52 visit
or
II. completed the Week 12 visit and whose UC condition in the opinion of the Investigator has not improved or has worsened, compared with baseline (Week 0/Day 1 in the parent study), provided their ES is ≥ 2 and they meet one of the following entry criteria:
• Rectal bleeding (RB) sub-score ≥ 2 at 2 timepoints at least 7 days and no more than 14 days apart
• RB + stool frequency (SF) sub-score ≥ 4 at 2 timepoints at least 7 days and no more than 14 days apart
• RB sub-score ≥ 2 or RB + SF sub-scores ≥ 4 (in any order) at 2 timepoints at least 7 days and no more than 14 days apart
Note: For subjects discontinuing prior to Week 52, an endoscopic evaluation is required to confirm eligibility for the OLE. An endoscopy should be scheduled upon the appearance of UC symptoms but no more than 14 days after the second timepoint for entry criteria above. A proctosigmoidoscopy does not need to be repeated if performed within the last 4 weeks
b. Subjects previously enrolled in study APD334-302 must have completed the Week 12 visit
2. Eligible women of childbearing potential must fulfill the following on Week0/Day 1:
a. Have a negative urine beta-human chorionic gonadotropin (β-hCG) pregnancy test
b. Not breastfeeding
3. Females must meet either a or b of the following criteria and males must meet criterion c to qualify for the study:
a. A nonpregnant female who is not of childbearing potential must meet 1 of the following:
- Postmenopausal, defined as no menses for 12 months without an alternative medical cause;
- Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
b. A female of childbearing potential must agree to using a highly effective contraception method during treatment and for 30 days following treatment that can achieve a failure rate of less than 1% per year when used consistently and correctly.
The following are considered highly effective birth control methods:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal.
- Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injected, or implanted.
- Intrauterine device (IUD).
- Intrauterine hormone-releasing system.
- Bilateral tubal occlusion.
- Vasectomized partner, provided that partner is the sole sexual partner of the WOCBP trial subject and that the vasectomized partner has received medical assessment of the surgical success.
- Sexual abstinence (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 study and the preferred and usual lifestyle of the subject.
Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable.
c. A male subject with a pregnant or nonpregnant female of childbearing potential partner must agree to using condoms during treatment and for 30 days following treatment.
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. Enrollment of subjects < 18 years should be conducted only if acceptable according to local laws and regulations.

E.4

Principal exclusion criteria

Subjects who meet ANY of the following exclusion criteria will NOT be eligible for enrollment into the study:
1. 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 (except when such an event is related to worsening disease) from parent study
3. Week0/Day 1 pre-dose sitting vital sign assessment: heart rate (HR) < 50 bpm OR systolic blood pressure (BP) < 90 mm Hg OR diastolic BP < 55 mm Hg
4. Week0/Day 1 pre-dose 12-lead ECG in the supine position showing a second or third-degree AV block, periods of asystole > 3 seconds, PR interval > 200 ms, or Fridericia’s corrected QT interval (QTcF) ≥ 450 ms (men) or QTcF ≥ 470 ms (women)
5. Subjects requiring colectomy during the parent study
6. Subjects requiring treatment with prohibited medications as defined in the parent study

E.5 End points

E.5.1

Primary end point(s)

• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
• Incidence and severity of laboratory abnormalities, and change from treatment baseline in laboratory values (hematology, serum chemistry, coagulation, and urinalysis)
• Incidence of vital sign abnormalities and changes from treatment 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 and 4-week Follow-up visit

E.5.2

Secondary end point(s)

• The proportion of subjects achieving clinical remission at Week 52 and 104 among subjects achieving clinical remission at study entry
• The proportion of subjects achieving clinical response at Weeks 52 and 104
• Change from baseline in the Total Mayo Score (TMS) at Weeks 52 and 104
• Change from baseline from Partial Mayo Score (PMS) at Weeks 52, 104, 156, 208 and 260
• The proportion of subjects achieving endoscopic improvement at Weeks 52 and 104

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 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

E.6.7

Pharmacodynamic

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

129

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

Chile

Switzerland

Moldova, Republic of

Ukraine

Australia

Belarus

Belgium

Bulgaria

Canada

China

Croatia

Czechia

Denmark

Estonia

France

Georgia

Germany

Hungary

India

Israel

Italy

Japan

Korea, Republic of

Latvia

Lebanon

Lithuania

Mexico

Netherlands

Poland

Portugal

Romania

Russian Federation

Serbia

Slovakia

South Africa

Spain

Thailand

Turkey

United Kingdom

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

Yes

F.1.1