Clinical Trial Results:
An Extension Study of APD334-003 in Patients with Moderately to Severely Active Ulcerative Colitis
|
Summary
|
|
EudraCT number |
2015-002109-12 |
Trial protocol |
LV ES GB HU CZ LT BE BG AT |
Global end of trial date |
01 Nov 2018
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
28 Oct 2019
|
First version publication date |
28 Oct 2019
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
APD334-005
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02536404 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Arena Pharmaceuticals, Inc.
|
||
Sponsor organisation address |
6154 Nancy Ridge Drive, San Diego, California, United States, 92121
|
||
Public contact |
Chris Cabell, Arena Pharmaceuticals, Inc., +1 858-210-3634, ccabell@arenapharm.com
|
||
Scientific contact |
Chris Cabell, Arena Pharmaceuticals, Inc., +1 858-210-3634, ccabell@arenapharm.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
30 Jul 2019
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
01 Nov 2018
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
01 Nov 2018
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To evaluate the long-term safety and tolerability of APD334 (etrasimod) in subjects with UC (ulcerative colitis) who have completed the APD334-003 study.
To evaluate the effect of etrasimod on achieving and maintaining clinical response and/or remission in subjects with UC after 46 weeks of treatment (including 12 weeks in APD334-003).
|
||
Protection of trial subjects |
The study was conducted in compliance with the ICH Guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements, the study protocol, and where applicable, Sponsor and/or CRO Standard Operating Procedures.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jan 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 14
|
||
Country: Number of subjects enrolled |
Romania: 1
|
||
Country: Number of subjects enrolled |
Spain: 4
|
||
Country: Number of subjects enrolled |
United Kingdom: 2
|
||
Country: Number of subjects enrolled |
Austria: 1
|
||
Country: Number of subjects enrolled |
Belgium: 3
|
||
Country: Number of subjects enrolled |
Bulgaria: 4
|
||
Country: Number of subjects enrolled |
Germany: 10
|
||
Country: Number of subjects enrolled |
Hungary: 8
|
||
Country: Number of subjects enrolled |
Latvia: 2
|
||
Country: Number of subjects enrolled |
United States: 20
|
||
Country: Number of subjects enrolled |
Canada: 3
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 3
|
||
Country: Number of subjects enrolled |
Russian Federation: 20
|
||
Country: Number of subjects enrolled |
Ukraine: 23
|
||
Worldwide total number of subjects |
118
|
||
EEA total number of subjects |
49
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
112
|
||
From 65 to 84 years |
6
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
To be eligible, subjects must have completed the APD334-003 study and met the eligibility criteria for APD334-005 at the time of entry. | ||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
This study was an open-label extension to APD334-003. Eligible subjects from APD334-003 were assigned to receive 2 mg etrasimod QD (once daily) for 34 weeks. Subjects who were enrolled under Protocol Amendment 2 followed a different study design - subjects were randomly assigned to receive placebo or 2 mg QD etrasimod. | ||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Treatment period 1 (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||
Blinding implementation details |
All eligible subjects were given the option to enroll and receive open-label treatment with 2 mg etrasimod once daily (QD).
|
||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
|
Arm title
|
Etrasimod | ||||||||||||||||||||||||
Arm description |
Subjects received 2 mg etrasimod tablets orally QD for 34 weeks. Subjects who were enrolled under Protocol Amendment 2 (28 September 2015) received placebo or 2 mg etrasimod tablets QD for 40 weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Etrasimod
|
||||||||||||||||||||||||
Investigational medicinal product code |
APD334
|
||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
Study treatment was provided in 40cc, induction sealed, high density polyethylene bottles with child resistant screw caps. Subjects were instructed to take their 2 mg etrasimod tablet QD, in the morning, on an empty stomach (after an overnight fast of approximately 8 hours), and to avoid eating for approximately 1 hour after dosing subjects were advised not to crush, break, chew, or dissolve the tablets and to take study medication with an adequate amount of water.
|
||||||||||||||||||||||||
|
Arm title
|
Placebo | ||||||||||||||||||||||||
Arm description |
Subjects who were enrolled under Protocol Amendment 2 (28 September 2015) received placebo or 2 mg etrasimod tablets QD for 40 weeks. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
Study treatment were provided in 40cc, induction sealed, high density polyethylene bottles with child resistant screw caps. Subjects were instructed to take their 2 mg etrasimod tablet QD (once daily) or placebo, in the morning, on an empty stomach (after an overnight fast of approximately 8 hours), and to avoid eating for approximately 1 hour after dosing. Subjects were advised not to crush, break, chew, or dissolve the tablets and to take study medication with an adequate amount of water.
Subjects enrolled under Protocol Amendment 2 (28 September 2015) were randomly assigned to receive placebo or 2 mg etrasimod QD.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment period 1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Etrasimod
|
||
Reporting group description |
Subjects received 2 mg etrasimod tablets orally QD for 34 weeks. Subjects who were enrolled under Protocol Amendment 2 (28 September 2015) received placebo or 2 mg etrasimod tablets QD for 40 weeks. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Subjects who were enrolled under Protocol Amendment 2 (28 September 2015) received placebo or 2 mg etrasimod tablets QD for 40 weeks. | ||
Subject analysis set title |
Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The Safety population will include all patients who received study medication in the extension study.
|
||
Subject analysis set title |
MITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
This MITT population consists of all patients, who received at least 1 dose of etrasimod or Placebo, had a baseline measurement, and had a post-enrollment measurement in the extension study for the specific efficacy endpoint being assessed. The MITT evaluable cohort was used for analysis of all proportion-based and all continuous efficacy variables.
|
||
|
|||||||||||||
End point title |
Number of SAE/AEs | ||||||||||||
End point description |
Treatment-emergent adverse events (AEs) up to 30 days following discontinuation of the study drug.
Treatment-emergent serious adverse events (SAEs) up to 30 days following discontinuation of the study drug.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From first dose in patients participating in APD334-005 study up to 30 days following discontinuation of the study drug - number of serious/treatment-emergent adverse events (AEs).
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis Plan, Ver 1.2, dated 27Nov18 | ||||||||||||
Statistical analysis description |
Descriptive statistics of 90% confidence interval (CI) for change or percent change from baseline of treatment with etrasimod.
|
||||||||||||
Comparison groups |
Etrasimod v Placebo
|
||||||||||||
Number of subjects included in analysis |
118
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0 | ||||||||||||
Method |
90% confidence interval | ||||||||||||
Confidence interval |
|||||||||||||
|
|||||||||||||
End point title |
Clinical response at week 12 and EOT | ||||||||||||
End point description |
Clinical response achieved at Week 12 and maintained at EOT in APD334-005.
Clinical Response is defined as achievement of clinical remission or satisfaction of the following criteria: decrease in the 3-component Mayo Clinic score (consisting of subscores for stool frequency, rectal bleeding and findings of flexible proctosigmoidoscopy) of >= 2 points and a decrease of >=30% with either a decrease of rectal bleeding of >=1 or rectal bleeding score of 0 or 1 compared to APD334-003 baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 and EoT.
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Clinical remission at EOT | ||||||||||||
End point description |
To evaluate the effect of etrasimod on achieving and maintaining clinical response and/or remission in subjects with UC after 46 weeks of treatment.
Clinical remission is defined as individual subscores of the 3-component Mayo Clinic score as follows: an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1 (excluding friability), a rectal bleeding score of 0 or 1, and a stool frequency score of 0 or 1 with a decrease of >= 1 point] compared to APD334-003 baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
EoT
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Clinical response at EOT | ||||||||||||
End point description |
Clinical Response is defined as achievement of clinical remission or satisfaction of the following criteria: decrease in the 3-component Mayo Clinic score (consisting of subscores for stool frequency, rectal bleeding and findings of flexible proctosigmoidoscopy) of >= 2 points and a decrease of >=30% with either a decrease of rectal bleeding of >=1 or rectal bleeding score of 0 or 1 compared to APD334-003 baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
EoT
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Clinical remission at week 12 and EOT | ||||||||||||
End point description |
Clinical remission is defined as individual subscores of the 3-component Mayo Clinic score as follows: an endoscopy score (using flexible proctosigmoidoscopy) of 0 or 1 (excluding friability), a rectal bleeding score of 0 or 1, and a stool frequency score of 0 or 1 with a decrease of >= 1 point] compared to APD334-003 baseline.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 and EoT
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events were followed up from the beginning of subject`s participation to 30 days following discontinuation of the study drug.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Etrasimod
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
28 Sep 2015 |
Amendment 02 (28 Sep 2015):
- Change in EU Legal representative
The EU Legal representative has changed from Covance Clinical and Periapproval Services Limited to Clinical Technology Centre (International) Limited.
- Change in applicant for regulatory and ethics committee applications
The applicant for regulatory and ethics committee applications has changed.
- Change in major responsibilities of the sponsor’s trial related duties.
|
||
20 Oct 2016 |
Amendment 03 (20 Oct 2016)
o Changed study duration from 52 weeks to 46 weeks in total
o Changed study design to single arm, open-label (2 mg once daily [q.d.]) for APD334-003 responders only and removal of Placebo group
o Updated secondary and exploratory outcome measures to reflect study duration of 46 weeks total (including the APD334-003 study)
o Changed time points i.e. removal of 7 and 8 hours post dose electrocardiogram (ECG) and vital signs assessments on Day 1; removal of 8 hours post dose pharmacokinetic (PK) sample on Day 1 and removal of weeks 20, 28, 36, 44 and 52
o Changed Week 52 to Week 46 as End-of-Treatment
o Removed Primary Safety and Secondary Efficacy hypotheses
o Removed sample size and power calculations
o Changed ‘Randomized’ to ‘Enrolled’ and removed treatment groups
o Removed between group differences and removal of formal statistical analysis |
||
27 Mar 2017 |
Amendment 04 (27 Mar 2017)
o Updated to add proportion of patients who achieve clinical response to secondary endpoints
o Updated to reflect APD334-003 completers to be eligible for APD334-005 study
The following exploratory endpoints have been added to the SAP in comparison with Protocol Amendment 04 to be consistent with the endpoints in the APD334-003 study:
• Change from baseline in the following measures:
o PMS#1, 3-component Mayo Clinic score
o PMS#2, 3-component Mayo Clinic score
o 2-component Mayo Clinic score (rectal bleeding and findings on endoscopy)
o Rectal bleeding subscore
o Stool frequency subscore
The following exploratory objectives have been added to the SAP in comparison with Protocol Amendment 04 to be consistent with the objectives in the APD334-003 study:
• PMS#1, 3-component Mayo Clinic score
• PMS#2, 3-component Mayo Clinic score
• 2-component Mayo Clinic score
The following subgroup analysis has been added to the SAP in comparison with Protocol Amendment 04:
• Biologic Agents (Integrin + TNFα antagonists) |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
