An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT02601300
• Recruitment Status: Completed
• First Posted: November 10, 2015
• Results First Posted: September 12, 2018
• Last Update Posted: October 17, 2018
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colitis, Ulcerative
• Intervention: Drug: GED-0301
• Enrollment: 41

Participant Flow

Recruitment Details	Participants were enrolled at 21 study centers within the United States, Bulgaria, Poland, Slovakia and Canada.
Pre-assignment Details	Participants were 18 years of age and older with active ulcerative colitis for 3 months prior to screening, had a modified Mayo score (MMS) ≥ 4 to ≤ 9 absolute rectal bleeding (RBS) subscore ≥ 1 at screening, a mayo endoscopic subscore ≥ 2 at screening and must have had a therapeutic failure or been intolerant to other therapies.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Period Title: Induction Phase
Started	41
Completed	38
Not Completed	3
Reason Not Completed
Lack of Efficacy	2
Protocol Violation	1
Period Title: Extension Phase
Started	35 [1]
Treated With IP	34
Completed	18
Not Completed	17
Reason Not Completed
Withdrawal by Subject	3
Adverse Event	4
Lack of Efficacy	10
[1] 3 completed induction phase; did not enter extension due to withdrawal and lack of efficacy

Baseline Characteristics

Arm/Group Title		Mongersen (Weeks 0-52)
Arm/Group Description		Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Baseline Participants		41
Baseline Analysis Population Description		Intent-to-treat population includes all participants who received at least 1 dose of investigational product.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	41 participants
		42.0 (11.91)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	41 participants
	Female	13 31.7%
	Male	28 68.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	41 participants
	Asian	1 2.4%
	Black or African American	2 4.9%
	White	37 90.2%
	Other	1 2.4%
Duration of Ulcerative Colitis; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	41 participants
		9.91 (9.107)
Baseline Modified Mayo Score (MMS) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	41 participants
		6.5 (1.50)
		[1] Measure Description: A modification to the total Mayo score (TMS) was implemented. The MMS was based on the stool frequency, rectal bleeding and endoscopy subscores of the total Mayo score, and excluded the Physician's Global subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points, with higher scores indicating greater disease severity.
Baseline Mayo Endoscopic Subscore [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	41 participants
		2.6 (0.50)
		[1] Measure Description: The Mayo endoscopic subscore is one of the components of the Mayo score and ranges from 0 - 3 points and is defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions); = Severe Disease (spontaneous bleeding, ulceration)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Score (MMS) at Week 8
Description	Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 8. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handing missing data was non-responder imputation (NRI) method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for clinical remission.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	17.1; (8.5 to 31.3)

2. Secondary Outcome

Title	Percentage of Participants Who Achieved a Modified Mayo Score of ≤ 2, With Rectal Bleeding Subscore (RBS) of 0 and Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore ≤ 1 at Week 8
Description	A MMS was used to evaluate disease activity using 3 components: stool frequency, rectal bleeding and endoscopy; the MMS ranges from 0-9 with higher scores indicating greater disease severity. Stool frequency subscore was defined as 0-3: 0 = Normal number of stools for patient; = 1-2 stools per day more than normal; = 3-4 stools more than normal; = 5 or more stools more than normal Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen; = Streaks of blood with stool less than half the time; = Obvious blood with stool most of the time; = Blood alone passes Endoscopic subscore: Findings were defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions); = Severe Disease (spontaneous bleeding, ulceration)
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for the MMS response.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	14.6; (6.9 to 28.4)

3. Secondary Outcome

Title	Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 at Week 8
Description	A Mayo endoscopic subscore of ≤ 1 was assessed and evaluated in participants who achieved a Mayo endoscopic subscore at Week 8. The endoscopy subscore findings are defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions); = Severe Disease (spontaneous bleeding, ulceration) The endoscopy scores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for Mayo Endoscopic Subscore.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	19.5; (10.2 to 34.0)

4. Secondary Outcome

Title	Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 by Individual Segment at Week 8
Description	A Mayo endoscopic subscore by individual segment (rectum, sigmoid, descending colon, transverse colon, ascending colon/cecum) of ≤ 1 was evaluated at week 8. The endoscopy subscore findings are defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions); = Severe Disease (spontaneous bleeding, ulceration) The endoscopy scores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. Only participants with sufficient data for response determination in each segment were included in the analysis.

Arm/Group Title		Mongersen (Weeks 0-52)
Arm/Group Description:		Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed		41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Rectum	Number Analyzed	37 participants
		27.0; (15.4 to 43.0)
Sigmoid	Number Analyzed	37 participants
		27.0; (15.4 to 43.0)
Descending Colon	Number Analyzed	35 participants
		54.3; (38.2 to 69.5)
Transverse Colon	Number Analyzed	28 participants
		60.7; (42.4 to 76.4)
Ascending Colon/Cecum	Number Analyzed	25 participants
		80.0; (60.9 to 91.1)

5. Secondary Outcome

Title	Percentage of Participants Who Achieved a Clinical Response in the Modified Mayo Score at Week 8
Description	Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was defined as: 0 = No blood seen; = Streaks of blood with stool less than half the time; = Obvious blood with stool most of the time; = Blood alone passes The daily bleeding score represents the most severe bleeding score represents the most severe bleeding of the day.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for MMS.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	36.6; (23.6 to 51.9)

6. Secondary Outcome

Title	Percentage of Participants Who Achieved a Mayo Endoscopic Response at Week 8
Description	Endoscopic response was defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore. The Mayo endoscopy subscore findings are defined as: 0 = Normal or inactive disease; = Mild Disease (erythema, decreased vascular pattern, mild friability); = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions); = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores were centrally reviewed. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for Mayo endoscopic response.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	31.7; (19.6 to 47.0)

7. Secondary Outcome

Title	Percentage of Participants Who Achieved a Clinical Remission in the Total Mayo Score (TMS) at Week 8
Description	Clinical remission in total Mayo score was defined as a total Mayo score of ≤ 2, with no individual subscore >1. The TMS is an instrument designed to measure disease activity of ulcerative colitis. The TMS ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.; Stool frequency subscore (SFS); Rectal bleeding subscore (RBS); Endoscopic subscore; Physician's Global Assessment (PGA)
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for Total Mayo score.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	9.8; (3.9 to 22.5)

8. Secondary Outcome

Title	Percentage of Participants Who Achieved a Clinical Response in the Total Mayo Score at Week 8
Description	Clinical response in the TMS was defined as a decrease from baseline in the TMS of ≥ 3 points and ≥ 30%, along with a reduction in the RBS of ≥ 1 point or an absolute RBS of ≤ 1 at Week 8. The TMS is an instrument designed to measure disease activity of ulcerative colitis. The TMS ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.; Stool frequency subscore; Rectal bleeding subscore; Endoscopic subscore; Physician's Global Assessment
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

The intent to treat population included all participants who received at least one dose of IP. The primary approach to handling missing data was NRI method, where participants who had insufficient data for response determination at Week 8 were considered non-responders for Total Mayo score.

Arm/Group Title	Mongersen (Weeks 0-52)
Arm/Group Description:	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase, followed by 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase, weeks 8 through 52). Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
Overall Number of Participants Analyzed	41
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	36.6; (23.6 to 51.6)

9. Secondary Outcome

Title	The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE)
Description	A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of mongersen and up to 28 days after the last mongersen 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.
Time Frame	From the first day of mongersen until 28 days after the last dose of IP or at follow-up visit, whichever occurred earlier; maximum duration of treatment was 56 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all participants who were enrolled and received at least 1 dose of IP.

Arm/Group Title	Mongersen Total Mongersen Exposure Period
Arm/Group Description:	Participants who received oral mongersen 160 mg tablets during the induction phase and the extension phase, with dosing starting on the first mongersen dose of the induction phase and ended at the last follow-up date up to 28 days after the last mongersen dose (either in the induction or the extension phase)
Overall Number of Participants Analyzed	41
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE	30 73.2%
Any IP-Related TEAE	6 14.6%
Any Severe TEAE	5 12.2%
Any Serious TEAE (SAE)	5 12.2%
Any Serious IP-Related TEAE	0 0.0%
Any TEAE Leading to IP Withdrawal	4 9.8%
Any TEAE Leading to IP Interruption	1 2.4%
Any TEAE Leading to Death	0 0.0%

Adverse Events

Time Frame	From the first day of mongersen until 28 days after the last dose of IP or at follow-up visit, whichever occurred earlier; the maximum duration of treatment was 56 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Mongersen (Induction Phase: Weeks 0-8)	Mongersen (Extension Phase: Weeks 8-52)
Arm/Group Description	Participants received oral mongersen 160 mg tablets daily for 8 weeks during the induction phase.	Participants received oral mongersen 160 mg tablets daily on an alternating dosing schedule for 4 weeks, followed by a 4 week break, (4 weeks on investigational product (IP), followed by 4 weeks off) for an additional 44 weeks during the extension phase. Participants who did not achieve at least a 20% decrease in a partial Mayo score (PMS) from baseline at Week 12 were discontinued from the study.
All-Cause Mortality
	Mongersen (Induction Phase: Weeks 0-8)	Mongersen (Extension Phase: Weeks 8-52)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/41 (0.00%)	0/34 (0.00%)
Serious Adverse Events
	Mongersen (Induction Phase: Weeks 0-8)	Mongersen (Extension Phase: Weeks 8-52)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/41 (2.44%)	4/34 (11.76%)
Blood and lymphatic system disorders
Anaemia † 1	0/41 (0.00%)	1/34 (2.94%)
Gastrointestinal disorders
Colitis † 1	0/41 (0.00%)	1/34 (2.94%)
Colitis ulcerative † 1	1/41 (2.44%)	1/34 (2.94%)
Hepatobiliary disorders
Cholecystitis acute † 1	0/41 (0.00%)	1/34 (2.94%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Mongersen (Induction Phase: Weeks 0-8)	Mongersen (Extension Phase: Weeks 8-52)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/41 (0.00%)	14/34 (41.18%)
Blood and lymphatic system disorders
Anaemia † 1	0/41 (0.00%)	2/34 (5.88%)
Gastrointestinal disorders
Colitis ulcerative † 1	0/41 (0.00%)	4/34 (11.76%)
Diarrhoea † 1	0/41 (0.00%)	2/34 (5.88%)
Nausea † 1	0/41 (0.00%)	2/34 (5.88%)
Vomiting † 1	0/41 (0.00%)	2/34 (5.88%)
Infections and infestations
Sinusitis † 1	0/41 (0.00%)	2/34 (5.88%)
Viral upper respiratory tract infection † 1	0/41 (0.00%)	3/34 (8.82%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/41 (0.00%)	2/34 (5.88%)
1 Term from vocabulary, MedDRA 20.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 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 days. Investigator must delete confidential information before submission and defer publication to permit patent applications.

Results Point of Contact

• Name/Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation
• Phone: 888-260-1599
• EMail: ClinicalTrialDisclosure@Celgene.com

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT02601300
• Other Study ID Numbers: GED-0301-UC-002
• First Submitted: November 6, 2015
• First Posted: November 10, 2015
• Results First Submitted: August 6, 2018
• Results First Posted: September 12, 2018
• Last Update Posted: October 17, 2018