The primary objective is to the safety of long term administration of etrasimod in subjects with moderately to severely active UC. The secondary objective is to assess the the long-term efficacy of etrasimod in subjects with moderately to severely…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The long-term safety profile of etrasimod will be assessed through the
following:
* Incidence of treatment emergent adverse events (TEAEs) 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
Secondary outcome
* The proportion of subjects achieving clinical remission at each of the
following weeks: Weeks 52, 104, 156, 208, and 260, among subject achieving
clinical remission at study entry
* The proportion of subjects achieving clinical response at each of the
following weeks: Weeks 52, 104, 156, 208, and 260
* The proportion of subjects achieving symptomatic remission at Weeks 52, 104,
156, 208, and 260
* The proportion of subjects achieving non invasive clinical response at each
of the following weeks: Weeks 12, 24, 36, 52, 104, 156, 208, and 260
* The proportion of subjects achieving in clinical remission at the following
weeks: Weeks 12, 52, 104, 156, 208, and 260, among subject achieving clinical
remission at study entry
* The proportion of subjects achieving symptomatic response at Weeks 12, 24,
36, 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
* The proportion of subjects achieving endoscopic improvement at each of the
following weeks: Weeks 52, 104, 156, 208, and 260
Background summary
Crohn*s disease (CD) and ulcerative colitis (UC) are chronic recurrent,
remittent, or progressive inflammatory conditions that may affect the entire
gastrointestinal tract (CD) and the colonic mucosa (UC), and are associated
with an increased risk for colon cancer. Treatment for subjects with UC is
generally for symptomatic care (relief of symptoms) and mucosal healing and
includes 5 major classes of medications: 5 aminosalicylic acid (5 ASA),
antibiotics, corticosteroids, immunomodulators, biologic therapies (eg, tumor
necrosis factor [TNF] inhibitors and anti integrins) and most recently Janus
kinase (JAK) inhibitor therapy.
An unmet medical need exists for the development of targeted therapies for the
treatment of UC with easily administered and stable oral drugs, particularly as
most patients treated with biologics experience inadequate responses or lose
responsiveness over time, even though their initial response may have been
positive.
Etrasimod (APD334) is an orally administered, selective, synthetic sphingosine
1 phosphate (S1P) receptor 1, 4, 5 modulator that is being developed to treat
immune-mediated inflammatory disorders, including UC. A Phase 2 study with
etrasimod in subjects with moderately to severely active UC demonstrated
consistent and clinically meaningful improvements in endpoint measures
reflecting cardinal symptoms of UC and objective findings of endoscopic
improvement.
Study objective
The primary objective is to the safety of long term administration of etrasimod
in subjects with moderately to severely active UC. The secondary objective is
to assess the the long-term efficacy of etrasimod in subjects with moderately
to severely active UC.
Study design
This is a multicenter, open label extension (OLE) study to evaluate the safety
and efficacy of etrasimod in subjects with moderately to severely active UC who
previously received double blinded treatment (either etrasimod 2 mg/day or
placebo) during participation in one of two Phase 3 double blinded, placebo
controlled studies (either Study APD334 301, APD334 302 and/or any other
qualified region-specific studies).
Subjects are eligible for enrollment into the OLE study only if they completed
Study APD334 301 (ie, through Week 52) or they met any of the criteria related
to disease worsening as detailed in the inclusion criteria or completed Study
APD334 302 (through Week 12).
The OLE study consists of:
1. An Open Label Treatment Period (up to 260 weeks [up to 5 years]) and
2. A 2 Week and 4-Week Follow Up visit (2 weeks and 4 weeks, respectively,
after Week 260/End of Treatment [EoT] visit).
All subjects will receive etrasimod 2 mg once daily for up to 260 weeks (up to
5 years) or until marketing authorization is obtained in their country.
Intervention
Etrasimod, 2 mg tablets, by mouth, once daily.
Study burden and risks
Common adverse events that have been reported with S1P receptor modulators
include bradycardia at the first dose or atrioventricular (AV) block, macular
edema, hypertension, headache, cough, dyspnea, back pain, influenza, and
diarrhea.
Safety and tolerability of etrasimod has been evaluated in Phase 1 studies with
healthy adult subjects at single doses up to 5 mg and repeat doses up to 3 mg
once daily and in Phase 2 studies in subjects with UC (refer to the latest IB).
Etrasimod was found to be safe and well tolerated in these studies, with no
clinically significant safety concerns with respect to vital signs,
electrocardiograms (ECGs), pulmonary function tests (PFTs), ophthalmoscopy, or
clinical laboratory tests. Etrasimod produced a dose dependent sustained
decrease in total lymphocyte count, which is expected given etrasimod*s
mechanism of action. Lymphocyte counts returned to approximately baseline
levels within 7 days after the last dose.
25 visits will take place in 5 years. If the subject completes all visites, a
total amount of 572 ml of blood will be drawn. Participant will have at least
one proctosigmoidoscopy/colonoscopy, biopsy, eye examination (ophthalmoscopy)
and optical coherence tomography (OCT) performed throughout the study.
Nancy Ridge Drive 6154
San Diego CA 92121
US
Nancy Ridge Drive 6154
San Diego CA 92121
US
Listed location countries
Age
Inclusion criteria
1. Must have met the eligibility criteria and have been enrolled in one of the
two Phase 3 studies (APD334-301 or APD334-302) or other qualified
region-specific studies and also meet the following additional criteria:
a. Subjects previously enrolled in Study APD334-301 must have either:
I. Completed the Week 12 visit whose UC condition in the opinion of the
Investigator has not improved or has worsened, compared with baseline (Week
0/Day 1), may be eligible to entroll provided their ES is is * 2 and they meet
one of the following criteria:
* Rectal bleeding (RB) subscore * 2 at 2 timepoints at least 7 days and no more
than 14 days apart
* RB + stool frequency (SF) subscore * 4 at 2 timepoints at least 7 days and no
more than 14 days apart
* RB subscore * 2 or RB + SF subscores * 4 (in any order) at 2 timepoints at
least 7 days and no more than 14 days apart
or
II. Completed the Week 52 visit
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 APD334-302 must have completed the Week 12
visit
2. Eligible women of childbearing potential must fulfill the following on Day 1:
a. Have a negative urine beta human chorionic gonadotropin (*-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 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 participant 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 must agree to using condoms during treatment and for 4 weeks
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.
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 (except when such
an event is related to UC flare) from parent study
3. 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. 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. Subjects requiring partial or total colectomy during the parent study
6. Subjects requiring treatment with prohibited concomitant medications as
defined in the parent study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003987-29-NL |
| Other | IND 125154 |
| CCMO | NL70302.056.19 |