November 6, 2015
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November 10, 2015
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August 6, 2018
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September 12, 2018
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October 17, 2018
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December 14, 2015
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September 6, 2016 (Final data collection date for primary outcome measure)
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Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Score (MMS) at Week 8 [ Time Frame: Baseline to Week 8 ] 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.
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The proportion of subjects achieving clinical remission in the modified Mayo score (MMS), defined as a MMS of ≤ 2, with no individual subscore > 1 [ Time Frame: Up to approximately week 8 ] The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points
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- 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 [ Time Frame: Baseline to Week 8 ]
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)
- Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 at Week 8 [ Time Frame: Baseline to Week 8 ]
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.
- Percentage of Participants Who Achieved a Mayo Endoscopic Subscore of ≤ 1 by Individual Segment at Week 8 [ Time Frame: Baseline to Week 8 ]
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.
- Percentage of Participants Who Achieved a Clinical Response in the Modified Mayo Score at Week 8 [ Time Frame: Baseline to Week 8 ]
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.
- Percentage of Participants Who Achieved a Mayo Endoscopic Response at Week 8 [ Time Frame: Baseline and Week 8 ]
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.
- Percentage of Participants Who Achieved a Clinical Remission in the Total Mayo Score (TMS) at Week 8 [ Time Frame: Baseline to Week 8 ]
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)
- Percentage of Participants Who Achieved a Clinical Response in the Total Mayo Score at Week 8 [ Time Frame: Baseline to Week 8 ]
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
- The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) [ 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 ]
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.
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- The proportion of subjects achieving a modified Mayo score (MMS) of ≤ 2, with rectal bleeding subscore of 0 and stool frequency subscore and Mayo endoscopic subscore ≤ 1 [ Time Frame: Up to approximately 8 weeks ]
The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points
- The proportion of subjects achieving a Mayo endoscopic subscore ≤ 1 [ Time Frame: Up to approximately 8 weeks ]
Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points
- The proportion of subjects achieving a Mayo endoscopic subscore by individual segment (rectum, sigmoid, descending colon, transverse [ Time Frame: Up to approximately 8 weeks ]
Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points
- The proportion of subjects achieving clinical response in the MMS, defined as a decrease from baseline of at least 2 points and at least 25%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS ≤ 1 [ Time Frame: Up to approximately 8 weeks ]
The MMS is based on the stool frequency subscore, rectal bleeding subscore and endoscopy subscore of the total Mayo score, and excludes the Physician's Global Assessment (PGA) subscore. The modified Mayo score ranges from 0 to 9 points
- The proportion of subjects achieving endoscopic response, defined as a decrease from baseline of at least 1 point in the Mayo endoscopic subscore [ Time Frame: Up to approximately 8 weeks ]
Mayo endoscopic subscore is one of Mayo score component and it ranges from 0 to 3 points
- The proportion of subjects achieving clinical remission in the total Mayo score (TMS), defined as a TMS of ≤ 2, with no individual subscore > 1 [ Time Frame: Up to approximately 8 weeks ]
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
- The proportion of subjects achieving clinical response in the total Mayo score (TMS), defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the RBS of at least 1 point or an absolute RBS of ≤ 1 [ Time Frame: Up to approximately 8 weeks ]
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
- Adverse Events (AEs) [ Time Frame: Up to approximately 52 weeks ]
Assessed by the type, frequency and severity of adverse events, and its relationship to investigational product (IP), discontinuation due to adverse events, and clinically significant changes in vital signs, Electrocardiograms (ECGs), and/or laboratory findings
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Not Provided
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Not Provided
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An Efficacy and Safety Study of Mongersen (GED-0301) in Subjects With Active Ulcerative Colitis
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A Phase 2, Open-Label, Multicenter Study to Explore the Efficacy and Safety of MONGERSON (GED-0301) in Subjects With Active Ulcerative Colitis.
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This is a phase 2, open-label, multicenter study to explore the efficacy and safety of oral GED- 0301 in subjects with active UC, defined as a modified Mayo score (MMS) ≥ 4 and ≤ 9 and a Mayo endoscopic subscore≥ 2.
Approximately 40 subjects will be enrolled using an Interactive Voice Response System (IVRS) or an Interactive Web Response System (IWRS) to receive open-label, oral GED-0301 160 mg for duration of 52 week treatment. Enrollment of subjects with previous exposure to TNF-α blockers will be limited to approximately 15 subjects. The number of subjects with extensive colitis is targeted to comprise approximately 50% of the entire study population.
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Eligible subjects will have the Baseline Visit (Week 0/ Visit 2) and receive the following treatments:
- Induction Phase - GED-0301 160 mg once daily (QD) for 8 weeks;
- Extension Phase - GED-0301 160 mg on alternating dosing schedule (GED-0301 160 mg QD for 4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional 44 weeks. Subjects who do not achieve at least a 20% decrease in partial mayo score (PMS) from baseline at Week 12 will be discontinued from the study.
Clinical, safety, and pharmacokinetic (PK) data will be evaluated on an ongoing basis, however, if the response to treatment is lower than expected (eg, ≤2 subjects achieving clinical remission based on modified Mayo score (MMS)) when 50% of the subjects complete Week 8, or discontinue before Week 8, the study team will review available data (clinical, safety, and PK) to evaluate if the study conduct should be modified.
This evaluation will be based on clinical judgment and the following guidance
- Consider starting a new cohort of subjects using a QD dose up to 320 mg if there is endoscopic or histologic evidence of proximal colon benefit but limited or no distal colon drug exposure/efficacy. Also, there is evidence of potential overall efficacy (total Mayo score (TMS), MMS,PMS) outcomes and acceptable safety (adverse events (AEs)/vitals/clinical laboratory test results) and exposure (PK).
- Consider to terminate the study if there is no evidence of drug exposure/efficacy in the colon observed by endoscopy or biopsy nor evidence of potential overall efficacy (TMS, MMS, PMS) outcomes or unacceptable safety(AEs/labs/vitals) or exposure (PK).
- Continue the study with the GED-0301 160 mg QD dose. If the GED-0301 160 mg QD dose group is discontinued and a new dose group is added, an additional 40 subjects will be enrolled in the new dose group. Subjects enrolled subsequent to the decision to adjust the dose of GED-0301, will receive the following treatments:
- Induction Phase - GED-0301, up to 320 mg QD, for 8 weeks;
- Extension Phase- GED-0301, up to 320 mg on alternating dosing schedule (GED-0301, up to 320 mg QD for 4 weeks, followed by 4 weeks without GED-0301 treatment) for an additional 44 weeks. Subjects who do not achieve at least a 20% decrease in the PMS from baseline at Week 12 will be discontinued from the study. Actively enrolled subjects will not be affected by the dose adjustment. Subjects receiving corticosteroids at baseline will start tapering their corticosteroids at Week 8 (the end of the Induction Phase) if they achieve clinical response, defined as a decrease from baseline 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 in the MMS. The endoscopy subscore assessed by the investigator will be used for the calculation of the Week 8 MMS.
The study will consist of 4 phases:
- Screening Phase - up to 4 weeks
- Induction Phase - 8 weeks
- Extension Phase - 44 weeks
- Observational Follow-up Phase - 4 weeks Subjects who complete the Extension Phase, and those subjects who prematurely discontinue from the study for any reason, will enter the post-treatment Observational Follow-up Phase, the 4-week period after the last dose of Investigational Product(IP). The study will be conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practices (GCPs).
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Interventional
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Phase 2
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Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Colitis, Ulcerative
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Drug: GED-0301
Other Name: Mongersen
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Experimental: GED-0301 160 mg once daily (QD)
Patients will receive oral GED-0301 160 mg once daily (QD)for duration of 52 week treatment.
Intervention: Drug: GED-0301
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Not Provided
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Completed
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41
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40
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August 8, 2017
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September 6, 2016 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
Inclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Bulgaria, Canada, Hungary, Poland, Slovakia, United States
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NCT02601300
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GED-0301-UC-002
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No
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Not Provided
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Not Provided
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Celgene
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Celgene Corporation
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Celgene
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Celgene Corporation
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Not Provided
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Study Director: |
Keith Usiskin, M.D |
Celgene Corporation |
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Celgene
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October 2018
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