Trial Outcomes & Findings for Efficacy and Safety Study of Mongersen (GED-0301) for the Treatment of Subjects With Active Crohn's Disease (NCT NCT02596893)

Last Updated: 2019-08-28

Results Overview

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score \< 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the affect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

701 participants

Primary outcome timeframe

Week 12

Results posted on

2019-08-28

Participant Flow

Participants were enrolled at study centers within the United States and Canada, Australia, Eastern and Western Europe, Korea and Russia.

Treatment assignment at baseline (Week 0) was stratified based on concomitant use of corticosteroids (yes/no), concomitant use of immunosuppressants (yes/no) or and previous exposure to biologics (yes/no),

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Overall Double-Blind Period Weeks 0-52 STARTED	174	176	176	175
Overall Double-Blind Period Weeks 0-52 COMPLETED	10	8	14	9
Overall Double-Blind Period Weeks 0-52 NOT COMPLETED	164	168	162	166
Follow-Up Period Weeks 0 to 52 STARTED	57	51	56	47
Follow-Up Period Weeks 0 to 52 COMPLETED	57	51	56	47
Follow-Up Period Weeks 0 to 52 NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Overall Double-Blind Period Weeks 0-52 Study Terminated by Sponsor	61	56	48	58
Overall Double-Blind Period Weeks 0-52 Adverse Event	11	15	15	12
Overall Double-Blind Period Weeks 0-52 Pregnancy	0	0	0	1
Overall Double-Blind Period Weeks 0-52 Lack of Efficacy	15	14	14	13
Overall Double-Blind Period Weeks 0-52 Withdrawal by Subject	10	4	13	5
Overall Double-Blind Period Weeks 0-52 Miscellaneous	1	2	0	2
Overall Double-Blind Period Weeks 0-52 Lost to Follow-up	0	1	1	1
Overall Double-Blind Period Weeks 0-52 Non-Compliance with Study Drug	0	0	1	2
Overall Double-Blind Period Weeks 0-52 Death	0	0	1	0
Overall Double-Blind Period Weeks 0-52 Protocol Violation	0	0	0	2
Overall Double-Blind Period Weeks 0-52 Early Escape	66	76	69	70

Baseline Characteristics

1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=174 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=175 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.	Total n=701 Participants Total of all reporting groups
Age, Continuous	38.5 Years STANDARD_DEVIATION 12.88 • n=174 Participants	37.6 Years STANDARD_DEVIATION 12.84 • n=176 Participants	39.6 Years STANDARD_DEVIATION 12.90 • n=176 Participants	38.2 Years STANDARD_DEVIATION 12.47 • n=175 Participants	38.5 Years STANDARD_DEVIATION 12.77 • n=701 Participants
Sex: Female, Male Female	76 Participants n=174 Participants	98 Participants n=176 Participants	92 Participants n=176 Participants	80 Participants n=175 Participants	346 Participants n=701 Participants
Sex: Female, Male Male	98 Participants n=174 Participants	78 Participants n=176 Participants	84 Participants n=176 Participants	95 Participants n=175 Participants	355 Participants n=701 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=174 Participants	0 Participants n=176 Participants	1 Participants n=176 Participants	0 Participants n=175 Participants	2 Participants n=701 Participants
Race/Ethnicity, Customized Asian	11 Participants n=174 Participants	2 Participants n=176 Participants	8 Participants n=176 Participants	8 Participants n=175 Participants	29 Participants n=701 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=174 Participants	4 Participants n=176 Participants	2 Participants n=176 Participants	2 Participants n=175 Participants	12 Participants n=701 Participants
Race/Ethnicity, Customized White	150 Participants n=174 Participants	165 Participants n=176 Participants	152 Participants n=176 Participants	158 Participants n=175 Participants	625 Participants n=701 Participants
Race/Ethnicity, Customized Not Collected or Reported	5 Participants n=174 Participants	4 Participants n=176 Participants	9 Participants n=176 Participants	5 Participants n=175 Participants	23 Participants n=701 Participants
Race/Ethnicity, Customized Other (No classification)	3 Participants n=174 Participants	1 Participants n=176 Participants	4 Participants n=176 Participants	2 Participants n=175 Participants	10 Participants n=701 Participants
Duration of Crohn's Disease	9.57 Years STANDARD_DEVIATION 9.106 • n=174 Participants	8.63 Years STANDARD_DEVIATION 7.877 • n=176 Participants	9.84 Years STANDARD_DEVIATION 8.746 • n=176 Participants	10.15 Years STANDARD_DEVIATION 9.353 • n=175 Participants	9.54 Years STANDARD_DEVIATION 8.786 • n=701 Participants
Baseline Crohn's Disease Activity (CDAI) Score	307.9 Units on a Scale STANDARD_DEVIATION 64.31 • n=173 Participants • 1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.	292.8 Units on a Scale STANDARD_DEVIATION 69.33 • n=175 Participants • 1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.	308.3 Units on a Scale STANDARD_DEVIATION 65.50 • n=176 Participants • 1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.	309.9 Units on a Scale STANDARD_DEVIATION 66.32 • n=175 Participants • 1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.	304.7 Units on a Scale STANDARD_DEVIATION 66.61 • n=699 Participants • 1 participant CDAI was missing in the placebo arm and the GED-0301 160 mg/ 40 mg 4 Week Alt arm.
Baseline Endoscopic Score for Crohn's Disease (Central Read)	14.4 Units on a Scale STANDARD_DEVIATION 7.88 • n=173 Participants • 1 participant endoscopic was missing in the placebo arm.	14.3 Units on a Scale STANDARD_DEVIATION 8.41 • n=176 Participants • 1 participant endoscopic was missing in the placebo arm.	13.8 Units on a Scale STANDARD_DEVIATION 7.69 • n=176 Participants • 1 participant endoscopic was missing in the placebo arm.	14.5 Units on a Scale STANDARD_DEVIATION 8.30 • n=175 Participants • 1 participant endoscopic was missing in the placebo arm.	14.2 Units on a Scale STANDARD_DEVIATION 8.06 • n=700 Participants • 1 participant endoscopic was missing in the placebo arm.

PRIMARY outcome

Timeframe: Week 12

Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor; the Non-responder Imputation (NRI)

Outcome measures

Outcome measures
Measure	Placebo n=160 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=162 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=164 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=157 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Percentage of Participants Who Achieved a Clinical Remission at Week 12	25.0 Percentage of Participants Interval 18.9 to 32.2	25.3 Percentage of Participants Interval 19.2 to 32.5	21.3 Percentage of Participants Interval 15.8 to 28.2	21.7 Percentage of Participants Interval 15.9 to 28.7

SECONDARY outcome

Timeframe: Week 52

Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

Clinical remission is defined as a CDAI score \< 150 and is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=120 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=128 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=117 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Percentage of Participants Who Achieved Clinical Remission at Week 52	5.3 percentage of participants Interval 2.5 to 11.1	2.5 percentage of participants Interval 0.9 to 7.1	9.4 percentage of participants Interval 5.4 to 15.7	3.4 percentage of participants Interval 1.3 to 8.5

SECONDARY outcome

Timeframe: Week 52

Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

An endoscopic response-50 is defined as a reduction of at least 50% compared with baseline in simple endoscopic score for Crohn's Disease (SES-CD). The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: * Ulcers scored as: 0: no 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=120 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=128 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=117 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Percentage of Participants With Endoscopic Response-50 Centrally Read at Week 52	3.5 percentage of participants Interval 1.4 to 8.7	0.8 percentage of participants Interval 0.1 to 4.6	1.6 percentage of participants Interval 0.4 to 5.5	1.7 percentage of participants Interval 0.5 to 6.0

SECONDARY outcome

Timeframe: Week 12

Population: ITT population; Includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

A clinical response is defined as a CDAI score decrease from baseline ≥ 100 points. The CDAI is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=160 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=162 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=164 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=157 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Percentage of Participants Who Achieved a Clinical Response at Week 12	44.4 percentage of participants Interval 36.9 to 52.1	32.1 percentage of participants Interval 25.4 to 39.6	34.1 percentage of participants Interval 27.3 to 41.7	33.8 percentage of participants Interval 26.8 to 41.5

SECONDARY outcome

Timeframe: Week 4

Population: ITT Population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

A clinical response is defined as a decrease from baseline in CDAI ≥ 100 points. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=169 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=172 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=170 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=169 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Percentage of Participants Who Achieved a Clinical Response at Week 4	34.3 percentage of participants Interval 27.6 to 41.8	28.5 percentage of participants Interval 22.3 to 35.6	32.4 percentage of participants Interval 25.8 to 39.7	27.8 percentage of participants Interval 21.6 to 35.0

SECONDARY outcome

Timeframe: Week 4

Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

A clinical remission is a CDAI score \< 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=169 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=172 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=170 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=169 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Percentage of Participants Who Achieved a Clinical Remission at Week 4	20.1 percentage of participants Interval 14.8 to 26.8	18.6 percentage of participants Interval 13.5 to 25.1	16.5 percentage of participants Interval 11.6 to 22.8	15.4 percentage of participants Interval 10.7 to 21.6

SECONDARY outcome

Timeframe: Week 52

Population: ITT population; includes participants who received oral corticosteroids at baseline and had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

The percentage of participants who were receiving oral corticosteroids for Crohn's disease, at baseline and achieved a clinical remission (CDAI score \<150) at Week 52 without corticosteroids. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=39 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=43 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=42 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Percentage of Participants Who Achieved a Corticosteroid-Free Clinical Remission at Week 52	2.2 percentage of participants Interval 0.4 to 11.3	0.0 percentage of participants Interval 0.0 to 9.0	7.0 percentage of participants Interval 2.4 to 18.6	2.4 percentage of participants Interval 0.4 to 12.3

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

For participants who achieved a sustained clinical remission at both week 12 and 52, the clinical remission is a CDAI score \< 150. The Crohn's Disease Activity Index is used to quantify the signs and symptoms of Crohn's disease and the effect on patient's quality of life. It consists of 8 variables which include patient reported outcomes over a 7 day period and physician assessments which are scored numerically and weighted. Scores range from 0 to 600, with the most severe disease defined \>450.

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=120 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=128 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=117 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Percentage of Participants Who Achieved a Sustained Clinical Remission at Both Week 12 and 52	2.7 percentage of participants Interval 0.9 to 7.5	2.5 percentage of participants Interval 0.9 to 7.1	3.9 percentage of participants Interval 1.7 to 8.8	1.7 percentage of participants Interval 0.5 to 5.0

SECONDARY outcome

Timeframe: Week 0, Week 12

Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

An endoscopic response-25 is defined as a reduction of at least 25% compared with baseline in simple endoscopic score for Crohn's disease (SES-CD). The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: * Ulcers scored as: 0: no 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Outcome measures

Outcome measures
Measure	Placebo n=160 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=162 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=164 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=157 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Percentage of Participants With Endoscopic Response-25 Centrally Read at Week 12	28.1 percentage of participants Interval 21.7 to 35.5	17.3 percentage of participants Interval 12.2 to 23.8	27.4 percentage of participants Interval 21.2 to 34.7	24.2 percentage of participants Interval 18.2 to 31.5

SECONDARY outcome

Timeframe: Week 52

Population: ITT population; includes participants who had either completed that timepoint visit or discontinued at any time due to reasons other than study terminated by sponsor. NRI.

Endoscopic remission is defined as a simple endoscopic score for Crohn's disease (SES-CD) of ≤2 at the specified timeframe. The SES-CD assesses the size of mucosal ulcers, the extent of ulcerated surface, the extent of affected surface, and the presence and type of narrowings. Scores range from 0 to 60 with higher scores reflecting more severe disease. The SES-CD calculations include: * Ulcers scored as: 0: no 1. aphthous (0.1-0.5 cm) 2. large (0.5-2 cm) 3. very large (\>2 cm) * Surface involved disease 0: 0% 1. \<50% 2. 50-75% 3. \>75% Surface involved by ulcerations: 0: 0% 1. \<10% 2. 10-30% 3. \>30% - Narrowings: 0: No 1. Single, can be passed 2. Multiple, can be passed 3. Cannot be passed Grand Total = SES-CD score

Outcome measures

Outcome measures
Measure	Placebo n=113 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=120 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=128 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=117 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Percentage of Participants With Endoscopic Remission Centrally Read at Week 52	2.7 percentage of participants Interval 0.9 to 7.5	0.8 percentage of participants Interval 0.1 to 4.6	0.8 percentage of participants Interval 0.1 to 4.3	0.9 percentage of participants Interval 0.2 to 4.7

SECONDARY outcome

Timeframe: From the first day of GED-0301 until 28 days after the last dose of investigational product (IP); maximum treatment duration was 52.6 weeks

Population: The safety population consisted of all participants who were randomized and received at least 1 dose of IP.

A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of GED-0301 and up to 28 days after the last GED-0301 dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event.

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=175 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any TEAE	124 Participants	128 Participants	129 Participants	113 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any IP-Related TEAE	31 Participants	35 Participants	30 Participants	20 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any Severe TEAE	14 Participants	22 Participants	21 Participants	15 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any Serious TEAE (SAE)	16 Participants	28 Participants	22 Participants	15 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any Serious IP-Related TEAE	3 Participants	2 Participants	2 Participants	0 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any TEAE Leading to IP Withdrawal	11 Participants	15 Participants	16 Participants	12 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any TEAE Leading to IP Interruption	4 Participants	4 Participants	5 Participants	4 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) From Week 0 to Week 52 Any TEAE Leading to Death	0 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From the first day of GED-0301 until 28 days after the last dose of IP; maximum treatment duration was 52.6 weeks

Population: The safety population consisted of all participants who were randomized and received at least 1 dose of IP

A TEAE was defined as any AE occurring or worsening on or after the first dose of GED-0301 and up to 28 days after the last GED-0301 dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=176 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=175 Participants Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
The Number of Participants Who Discontinued IP Due to an Treatment Emergent Adverse Events	11 participants	15 participants	16 participants	12 participants

Adverse Events

Placebo

Serious events: 16 serious events

Other events: 78 other events

Deaths: 0 deaths

GED-0301 160 mg / GED-0301 40 mg 4 Week Alt

Serious events: 28 serious events

Other events: 72 other events

Deaths: 0 deaths

GED-0301 160 mg / GED-0301 40 mg

Serious events: 22 serious events

Other events: 74 other events

Deaths: 1 deaths

GED-0301 160 mg / GED-0301 160 mg 4 Week Alt

Serious events: 15 serious events

Other events: 63 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=174 participants at risk Participants received placebo daily up to week 52.	GED-0301 160 mg / GED-0301 40 mg 4 Week Alt n=176 participants at risk Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 40 mg daily for 4 weeks, up to week 52.	GED-0301 160 mg / GED-0301 40 mg n=176 participants at risk Participants received GED-0301 160 mg daily for 12 weeks, followed by continuous GED-0301 40 mg daily, up to week 52.	GED-0301 160 mg / GED-0301 160 mg 4 Week Alt n=175 participants at risk Participants received GED-0301 160 mg daily for 12 weeks, followed by alternating placebo daily for 4 weeks and GED-0301 160 mg daily for 4 weeks, up to week 52.
Gastrointestinal disorders ABDOMINAL PAIN	10.9% 19/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	11.4% 20/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.0% 14/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.6% 15/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Gastrointestinal disorders CROHN'S DISEASE	8.6% 15/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.0% 14/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.0% 14/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.6% 15/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Gastrointestinal disorders DIARRHOEA	0.00% 0/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.7% 10/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Gastrointestinal disorders NAUSEA	6.9% 12/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.1% 9/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.7% 10/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.1% 9/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
General disorders PYREXIA	5.7% 10/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	7.4% 13/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.0% 14/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	8.6% 15/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	10.2% 18/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	8.0% 14/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	9.1% 16/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Musculoskeletal and connective tissue disorders ARTHRALGIA	8.6% 15/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	11.4% 20/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	13.1% 23/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	14.3% 25/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Musculoskeletal and connective tissue disorders BACK PAIN	5.2% 9/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	0.00% 0/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks
Nervous system disorders HEADACHE	8.6% 15/174 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.7% 10/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	6.8% 12/176 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks	5.1% 9/175 • From day 1 of GED-0301 until 28 days after the last dose of IP as well as those SAEs made known to the Investigator at any time thereafter that are suspected of being related to IP. Maximum treatment duration was 52.6 weeks

Additional Information

Anne Mcclain, Senior Manager

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Publication restrictions are in place

Restriction type: OTHER