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Safety and Efficacy of Andecaliximab (GS-5745) in Adults With Moderately to Severely Active Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02520284
Recruitment Status : Terminated
First Posted : August 11, 2015
Results First Posted : April 10, 2019
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE August 7, 2015
First Posted Date  ICMJE August 11, 2015
Results First Submitted Date  ICMJE March 18, 2019
Results First Posted Date  ICMJE April 10, 2019
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
For Cohort 1, Percentage of Participants With EBS Clinical Remission at Week 8 [ Time Frame: Week 8 ]
EBS clinical remission was defined as an endoscopic subscore of 0 or 1 (endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]); rectal bleeding subscore of 0 (rectal bleeding subscore range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes); and at least a 1-point decrease in stool frequency from baseline to achieve a subscore of 0 or 1 (stool frequency subscore range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal).
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
  • For Cohort 1, proportion of participants achieving remission at Week 8 based on select mayo clinical score (MCS) measures [ Time Frame: Week 8 ]
  • For Cohort 2, proportion of participants achieving remission at Week 52 based on select MCS measures [ Time Frame: Week 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2019)
  • For Cohort 1, Percentage of Participants With MCS Remission at Week 8 [ Time Frame: Week 8 ]
    The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and physician's global assessment (PGA). The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. The MCS remission was defined as a MCS of ≤ 2 points and no individual subscore > 1 point. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
  • For Cohort 1, Percentage of Participants With MCS Response at Week 8 [ Time Frame: Week 8 ]
    The MCS was composed of subscores from endoscopy (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]), rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and PGA. The PGA acknowledged the participant's daily recollection of abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and the participant's performance status. The PGA score ranged from 0 to 3 with higher score indicating the severe disease. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening. The MCS response was defined as a MCS reduction of ≥ 3 points and at least 30% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1.
  • For Cohort 1, Percentage of Participants With Endoscopic Remission at Week 8 [ Time Frame: Week 8 ]
    Endoscopic remission was defined as endoscopic subscore of 0. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
  • For Cohort 1, Percentage of Participants With Endoscopic Response at Week 8 [ Time Frame: Week 8 ]
    Endoscopic response was defined as endoscopic subscore of 0 or 1. Endoscopic subscore range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease (spontaneous bleeding, ulceration).
  • For Cohort 1, Percentage of Participants With Mucosal Healing as Determined by the Geboes Histologic Scoring System at Week 8 [ Time Frame: Week 8 ]
    Mucosal healing was defined as elimination of ulcers/erosion, elimination of crypt destruction, elimination of intraepithelial neutrophils, elimination of lamina propria neutrophils, and reduction in lamina propria chronic inflammatory cells to at most a mild increase. When measured by the Geboes histologic scoring system, it was the selection of the following combined scores of ≤ 3 for Grade 0 (Structural Architectural Change), ≤ 1 for Grade 1 (Chronic Inflammatory Infiltrate), ≤ 3 for Grade 2A (Lamina Propria Eosinophils), and 0 for Grade 2B (Lamina Propria Neutrophils), Grade 3 (Neutrophils in Epithelium), Grade 4 (Crypt Destruction), and Grade 5 (Erosion or Ulceration). Total Geboes histologic score ranged from 0 to 22, with higher scores indicating greater disease severity.
  • For Cohort 1, Percentage of Participants With MCS Remission (Alternative Definition) at Week 8 [ Time Frame: Week 8 ]
    The MCS remission (alternative definition) was defined as a rectal bleeding (range: 0 to 3, where 0 = no blood seen and 3 = blood alone passes), stool frequency (range: 0 to 3, where 0 = normal number of stools and 3 = at least 5 stools more than normal), and PGA subscore (range: 0 to 3 with higher score indicating the severe disease) of 0, and an endoscopic subscore (range: 0 to 3, where 0 = normal or inactive disease and 3 = severe disease [spontaneous bleeding, ulceration]) of 0 or 1 for an overall MCS of ≤ 1. Total score for MCS ranged from 0 to 12 (sum of all subscores), with higher scores indicating disease worsening.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2015)
  • For Cohort 1, proportion of participants achieving MCS remission at Week 8 [ Time Frame: Week 8 ]
  • For Cohort 1, proportion of participants achieving MCS response at Week 8 [ Time Frame: Week 8 ]
  • For Cohort 1, proportion of participants achieving sustained clinical remission at Week 52 based on select MCS measures [ Time Frame: Weeks 8 and 52 ]
    Sustained clinical remission is defined as achieving clinical remission at both Week 8 and Week 52 based on select MCS measures.
  • For Cohort 1, proportion of participants achieving endoscopic remission at Week 8 [ Time Frame: Week 8 ]
  • For Cohort 1, proportion of participants achieving endoscopic response at Week 8 [ Time Frame: Week 8 ]
  • For Cohort 1, proportion of participants achieving mucosal healing as determined by histologic measures at Week 8 [ Time Frame: Week 8 ]
  • For Cohort 2, proportion of participants achieving MCS remission at Week 52 [ Time Frame: Week 52 ]
  • For Cohort 2, proportion of participants achieving corticosteroid-free clinical remission at Week 52 based on select MCS measures [ Time Frame: Week 52 ]
  • For Cohort 2, proportion of participants achieving endoscopic remission at Week 52 [ Time Frame: Week 52 ]
  • For Cohort 2, proportion of participants achieving mucosal healing as determined by histologic measures at Week 52 [ Time Frame: Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Andecaliximab (GS-5745) in Adults With Moderately to Severely Active Ulcerative Colitis
Official Title  ICMJE A Combined Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluating the Safety and Efficacy of GS-5745 in Subjects With Moderately to Severely Active Ulcerative Colitis
Brief Summary The primary objectives of this study are as follows: 1) To evaluate the efficacy of andecaliximab to induce endoscopy, rectal bleeding, and stool frequency (EBS) clinical remission at Week 8 (Cohort 1); 2) To evaluate the efficacy of andecaliximab to maintain EBS clinical remission at Week 52 (Cohort 2); and 3) To evaluate the safety and tolerability of andecaliximab. The study will consist of 3 parts: Induction Phase (Cohort 1), Maintenance Phase (Cohort 2), and an optional Extended Treatment Phase.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Biological: Andecaliximab
    Andecaliximab 150 mg administered via SC injection
    Other Name: GS-5745
  • Biological: Placebo
    Placebo matched to andecaliximab administered via SC injection
Study Arms  ICMJE
  • Experimental: Andecaliximab Every 2 Weeks
    Participants will receive andecaliximab 150 mg administered via subcutaneous (SC) injection alternating with matching placebo weekly for a total of 4 doses of andecaliximab. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.
    Interventions:
    • Biological: Andecaliximab
    • Biological: Placebo
  • Experimental: Andecaliximab Weekly
    Participants will receive andecaliximab 150 mg administered via SC injection once weekly for a total of 8 doses. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.
    Intervention: Biological: Andecaliximab
  • Placebo Comparator: Placebo
    Participants will receive placebo matched to andecaliximab administered via SC injection once weekly for a total of 8 doses. Based on Week 8 assessment results, participants will either continue in Blinded Maintenance Treatment phase or will be offered Open-Label andecaliximab 150 mg administered via SC injection weekly for up to Week 51.
    Interventions:
    • Biological: Andecaliximab
    • Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 12, 2016)
165
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2015)
1600
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Ulcerative Colitis (UC) confirmed on endoscopy
  • Moderately to severely active UC (Mayo Score 6-12)
  • May be receiving oral 5-aminosalicylate (ASA), oral corticosteroid, azathioprine, 6-mercaptopurine (MP), or methotrexate
  • Treatment failure with at least one of the following agents received: corticosteroids, immunomodulators, tumor necrosis factor-alpha (TNFα) antagonists, vedolizumab

Key Exclusion Criteria:

  • Diagnose of Crohn's disease or indeterminate colitis
  • Pregnant or lactating females
  • Any chronic medical condition (including, but not limited to cardiac or pulmonary disease, alcohol or drug abuse)
  • Exhibit severe UC / clinically significant active infection
  • History of malignancy in the last 5 years

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   Canada,   Czechia,   France,   Hungary,   Ireland,   Italy,   Korea, Republic of,   Latvia,   Netherlands,   New Zealand,   Poland,   Romania,   Russian Federation,   Slovakia,   South Africa,   Switzerland,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries Austria,   Croatia,   Czech Republic,   Germany,   Hong Kong,   Iceland,   Israel,   Serbia,   Spain,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT02520284
Other Study ID Numbers  ICMJE GS-US-326-1100
2014-005217-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Gilead Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP