ELEVATE UC OLE: An Open-Label Extension Study for Treatment of Moderately to Severely Active Ulcerative Colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arena Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

9 Jan 2020 → ongoing

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arena Pharmaceuticals Inc. a wholly owned subsidiary of Pfizer Inc.

External identifiers

EU CT number

2024-515156-21-00

EudraCT number

2018-003987-29

ClinicalTrials.gov

NCT03950232

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacoeconomic

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

Secondary objectives 1

1. The secondary objective is to assess the long-term efficacy of etrasimod in subjects with moderately to severely active UC.

Conditions and MedDRA coding

Ulcerative Colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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 Endoscopic Score (ES) is ≥ 2 and they meet one of the following entry criteria: - RB sub-score ≥ 2 at 2 timepoints at least 7 days and no more than 14 days apart. - RB + SF sub-scores ≥ 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 performed 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. 2. Eligible women of childbearing potential must fulfill the following on Week 0/Day 1: a. Have a negative urine beta-human chorionic gonadotropin (β-hCG) pregnancy test b. Not breastfeeding
3. 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 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 nonpregnant 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 female of childbearing potential 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. 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.

Exclusion criteria 6

1. 1. The Investigator considers the subject to be unsuitable for any reason to participate in the OLE study.
2. 2. Experienced an adverse event (AE) that led to discontinuation (except when such an event is related to worsening of disease) from parent study.
3. 3. Week 0/Day 1 pre-dose sitting vital sign assessment: heart rate (HR) < 50 bpm OR systolic BP < 90 mm Hg OR diastolic BP < 55 mm Hg.
4. 4. Week 0/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 Fridericia’s corrected QT interval (QTcF) ≥ 450 ms (men) or QTcF ≥ 470 ms (women).
5. 5. Subjects requiring colectomy during the parent study.
6. 6. Subjects requiring treatment with prohibited concomitant medications as defined in the parent study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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

Secondary endpoints 6

1. The proportion of subjects achieving clinical remission at Weeks 52 and 104
2. The proportion of subjects achieving clinical remission at Weeks 52 and 104, among subjects achieving clinical remission at study entry
3. The proportion of subjects achieving clinical response at Weeks 52 and 104
4. Change from baseline in the Total Mayo Score (TMS) at Weeks 52 and 104
5. Change from baseline in Partial Mayo Score (PMS) at each of the following weeks: Weeks 52, 104, 156, 208, and 260
6. The proportion of subjects achieving endoscopic improvement at Weeks 52 and 104

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arena Pharmaceuticals Inc.

Sponsor organisation

Arena Pharmaceuticals Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Arena Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Arena Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Third parties 14

Locations

14 EU/EEA countries · 60 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 117 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications