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

March 18, 2019 updated by: Gilead Sciences

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

165

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Footscray, Australia
      • Herston, Australia
      • Malvern, Australia
      • Melbourne, Australia
  • Belgium
      • Gent, Belgium
      • Leuven, Belgium
      • Mouscron, Belgium
  • Bulgaria
      • Pleven, Bulgaria
  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada
    • Ontario
      • Vaughan, Ontario, Canada
  • Czechia
      • Hradec Kralove, Czechia
  • France
      • Nantes, France
  • Hungary
      • Bekescsaba, Hungary
      • Budapest, Hungary
      • Debrecen, Hungary
  • Ireland
    • Leinster
      • Dublin, Leinster, Ireland
  • Italy
      • Rozzano, Italy
      • San Giovanni Rotondo, Italy
  • Korea, Republic of
      • Seoul, Korea, Republic of
      • Suwon-si, Korea, Republic of
  • Latvia
      • Daugavpils, Latvia
  • Netherlands
      • Amsterdam, Netherlands
  • New Zealand
      • Auckland, New Zealand
      • Wellington, New Zealand
    • Canterbury Region
      • Christchurch, Canterbury Region, New Zealand
  • Poland
      • Bialystok, Poland
      • Krakow, Poland
      • Lublin, Poland
      • Piaseczno, Poland
      • Poznan, Poland
      • Sopot, Poland
      • Sroda Wielkopolska, Poland
      • Tychy, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Romania
      • Bucharest, Romania
      • Timisoara, Romania
  • Russian Federation
      • Moscow, Russian Federation
      • Novosibirsk, Russian Federation
      • Rostov-on-Don, Russian Federation
      • Saint-Petersburg, Russian Federation
      • St. Petersburg, Russian Federation
  • Slovakia
      • Trencin, Slovakia
  • South Africa
    • Western Cape
      • Claremont, Western Cape, South Africa
  • Switzerland
      • Basel, Switzerland
      • Bern, Switzerland
  • Taiwan
      • Taichung, Taiwan
  • Ukraine
      • Kharkov, Ukraine
      • Kyiv, Ukraine
      • Lviv, Ukraine
      • Odessa, Ukraine
      • Vinnitsa, Ukraine
  • United Kingdom
      • Cambridge, United Kingdom
      • Oxford, United Kingdom
      • Prescot, United Kingdom
  • United States
    • Alabama
      • Dothan, Alabama, United States
    • Colorado
      • Wheat Ridge, Colorado, United States
    • Florida
      • Lauderdale Lakes, Florida, United States
      • Miramar, Florida, United States
      • Winter Park, Florida, United States
      • Zephyrhills, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Kansas
      • Topeka, Kansas, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Louisiana
      • Monroe, Louisiana, United States
    • Michigan
      • Ann Arbor, Michigan, United States
    • Minnesota
      • Plymouth, Minnesota, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • New Jersey
      • Egg Harbor Township, New Jersey, United States
    • New York
      • New York, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
      • Charlotte, North Carolina, United States
    • Ohio
      • Mentor, Ohio, United States
      • Rochester, Ohio, United States
    • Tennessee
      • Germantown, Tennessee, United States
      • Hermitage, Tennessee, United States
    • Texas
      • Arlington, Texas, United States
      • Baytown, Texas, United States
      • Houston, Texas, United States
      • Irving, Texas, United States
      • San Antonio, Texas, United States
      • Southlake, Texas, United States
    • Virginia
      • Charlottesville, Virginia, United States
      • Chesapeake, Virginia, United States
      • Norfolk, Virginia, United States
      • Richmond, Virginia, United States
    • Washington
      • Seattle, Washington, United States
    • Wisconsin
      • Wauwatosa, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Biological: Andecaliximab
Andecaliximab 150 mg administered via SC injection
Other Names:
  • GS-5745
Biological: Placebo
Placebo matched to andecaliximab administered via SC injection
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.
Biological: Andecaliximab
Andecaliximab 150 mg administered via SC injection
Other Names:
  • GS-5745
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.
Biological: Andecaliximab
Andecaliximab 150 mg administered via SC injection
Other Names:
  • GS-5745
Biological: Placebo
Placebo matched to andecaliximab administered via SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 8
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.
Week 8
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).
Week 8
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).
Week 8
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.
Week 8
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.
Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2015

Primary Completion (ACTUAL)

September 1, 2016

Study Completion (ACTUAL)

November 1, 2016

Study Registration Dates

First Submitted

August 7, 2015

First Submitted That Met QC Criteria

August 7, 2015

First Posted (ESTIMATE)

August 11, 2015

Study Record Updates

Last Update Posted (ACTUAL)

April 10, 2019

Last Update Submitted That Met QC Criteria

March 18, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-326-1100
  • 2014-005217-24 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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