| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Ulcerative Colitis |
| Colite ulcerosa |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ulcerative Colitis a form of inflammatory bowel disease. |
| 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 | No |
| 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) |
| 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 |
| To assess the long-term efficacy of etrasimod in subjects with moderately to severely active UC |
|
| E.2.3 | Trial contains a sub-study | No |
| 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 (ß-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 who is of childbearing potential must agree to using a highly
effective contraception method during treatment and for 4 weeks
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. |
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 (ß-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 who is of childbearing potential must agree to using a highly
effective contraception method during treatment and for 4 weeks
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. |
|
| 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. |
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 |
• 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 |
Settimane 2, 4, 8, 12, 24, 36, 52, 64, 76, 88, 104, 116, 128, 140, 156, 168, 180, 192, 2018, 220, 232, 244, 260,
2 settimane 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. |
• 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 |
| Settimane 12, 24, 36, 52, 104, 156, 208, e 260 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 21 |
| 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 | Information not present in EudraCT |
| 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 |
| Brazil |
| Canada |
| Chile |
| China |
| Colombia |
| Egypt |
| Georgia |
| India |
| Israel |
| Japan |
| Korea, Republic of |
| Lebanon |
| Mexico |
| Moldova, Republic of |
| Russian Federation |
| Serbia |
| South Africa |
| Taiwan |
| Thailand |
| Turkey |
| Ukraine |
| United States |
| Austria |
| Belgium |
| Bulgaria |
| Croatia |
| Czechia |
| Denmark |
| Estonia |
| France |
| Germany |
| Hungary |
| Italy |
| Latvia |
| Lithuania |
| Netherlands |
| Poland |
| Portugal |
| Romania |
| Slovakia |
| Spain |
| Switzerland |
| United Kingdom |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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