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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2, Open-Label, Multicenter Study to Explore the Efficacy and Safety of MONGERSON (GED-0301) in Subjects With Active Ulcerative Colitis.

Brief Summary:

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.

Detailed Summary:

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/l
  Sponsor: Celgene
  

  Current Primary Outcome: 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
  
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:

  • 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
  
  
  

  Original Secondary Outcome: Same as current
  
  Information By: Celgene
  

  Dates:
  Date Received: November 6, 2015
  Date Started: January 6, 2016
  Date Completion: August 11, 2017
  Last Updated: May 5, 2017
  Last Verified: May 2017