Safety and Efficacy of Andecaliximab in Participants With Moderately to Severely Active Crohn's Disease

A Phase 2, Double-blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of GS-5745 in Subjects With Moderately to Severely Active Crohn's Disease

This study will primarily evaluate the safety and efficacy of andecaliximab in adults with active Crohn's disease. The study will consist of a Double-Blind Phase of 8 weeks followed by an Open-Label Extension. Participants who complete the Double-Blind Phase will be eligible to enroll in the optional Open-Label Extension for an additional 44 weeks. Participants who complete Week 52 assessments will be eligible to enter the Extended Treatment Phase to continue treatment with andecaliximab for an additional 156 weeks.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Andecaliximab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia
      • Concord Repatriation General Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia
      • Flinders Medical Centre
  • Victoria
    • Footscray, Victoria, Australia
      • Footscray Hospital
    • Melbourne, Victoria, Australia
      • Gastroenterology/Colorectal Medicine & Genetics
• Canada
  • Victoria, Canada
    • PerCuro Clinical Research Ltd.
  • British Columbia
    • Victoria, British Columbia, Canada
      • PerCuro Clinical Research Ltd.
• Czechia
  • Hradec Kralove 2, Czechia
    • Hepato-Gastroenterologie HK s.r.o.
  • Praha 7, Czechia
    • Ibd Clinical And Research Centre-Iscare Ivf
• France
  • Clichy Cedex, France
    • Hopital Beaujon
  • Lille, France
    • CHRU de Lille
  • Nantes, France
    • Chu Hotel Dieu-Chu De Nantes
  • Saint Priest en Jarez, France
    • CHU de Saint Etienne - Hôpital Nord
• Germany
  • Kiel, Germany
    • Universitatsklinikum Schleswig-Holstein
  • Leipzig, Germany
    • Eugastro GmbH
  • Muenchen, Germany
    • Klinikum der Universität München
• Hungary
  • Bekescsaba, Hungary
    • Rethy Pal Hospital-Clinic Bekescsaba
  • Beri Balogh Adam, Hungary
    • Tolna Megye Balassa Janos Korhaz
  • Budapest, Hungary
    • Pannónia Magánorvosi Centrum Kft
  • Debrecen, Hungary
    • Debreceni Egyeterm Orvos es Egeszsegtudomanyi Centrum
• Italy
  • Roma, Italy
    • Università Campus Biomedico
  • Rozzano, Italy
    • Humanitas Research Hospital
• New Zealand
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Dunedin, New Zealand
    • Southern District Health Board
  • Wellington, New Zealand
    • Capital and Coast District Health board-Wellington hospital
• Poland
  • Bialystok, Poland
    • The Medical University of Bialystok Clinical
  • Lublin, Poland
    • Gastromed
  • Poznan, Poland
    • AI Centrum Medyczne
  • Poznan, Poland
    • CRC Sp. z o.o.
  • Sopot, Poland
    • Endoskopia Sp. z.o.o.
  • Warszawa, Poland
    • Centralny Szpital Kliniczny Mswia
  • Wroclaw, Poland
    • Lexmedica
• South Africa
  • Durban, South Africa
    • Parklands Medical Centre
  • Cape Town
    • Panorama, Cape Town, South Africa
      • Panorama Mediclinic Pvt Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universitari de Bellvitge
  • Fuenlabrada, Spain
    • Hospital Universitario de Fuenlabrada
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe de Valencia
• United Kingdom
  • Cambridge, United Kingdom
    • Cambridge University Hospitals NHS Foundation Trust
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Trust
  • Norfolk
    • Norwich, Norfolk, United Kingdom
      • Norfolk and Norwich University Hospital Nhs Foundation Trust
• United States
  • Alabama
    • Dothan, Alabama, United States
      • Digestive Health Specialists of the Southeast
  • Arizona
    • Scottsdale, Arizona, United States
      • Mayo Clinic
  • California
    • Los Angeles, California, United States
      • Cedars Sinai Medical Center
  • Colorado
    • Lone Tree, Colorado, United States
      • South Denver Gastroenterology
  • Florida
    • Miami, Florida, United States
      • University of Miami
    • Naples, Florida, United States
      • Gastroenterology Group Of Naples
  • Georgia
    • Macon, Georgia, United States
      • Gastroenterology Associates of Central Georgia, LLC
  • Indiana
    • Indianapolis, Indiana, United States
      • Medical Diagnostic Center (MDC)-Indiana University (IU) Health University Hospital
  • Iowa
    • Clive, Iowa, United States
      • Iowa Digestive Disease Center
  • Kansas
    • Topeka, Kansas, United States
      • Cotton-O'Neil Clinical Research Center, Digestive Health
  • Louisiana
    • Monroe, Louisiana, United States
      • Delta Research Partners
    • Shreveport, Louisiana, United States
      • Louisiana Research Center
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan
    • Chesterfield, Michigan, United States
      • Clinical Research Institute of Michigan, LLC
  • Minnesota
    • Rochester, Minnesota, United States
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Egg Harbor Township, New Jersey, United States
      • AGA Clinical Research Associates, LLC
  • New York
    • New York, New York, United States
      • Columbia University Medical Center/ New York Presbyterian
    • Poughkeepsie, New York, United States
      • Premier Medical Group of the Hudson Valley
    • Rochester, New York, United States
      • Mayo Clinic Rochester
  • North Carolina
    • Asheville, North Carolina, United States
      • Asheville Gastroenterology Associates
  • Ohio
    • Cincinnati, Ohio, United States
      • Consultants for Clinical Research
    • Mentor, Ohio, United States
      • Great Lakes Gastroenterology
  • Tennessee
    • Germantown, Tennessee, United States
      • Gastro One
    • Nashville, Tennessee, United States
      • Vanderbilt University Medical Center
  • Texas
    • Arlington, Texas, United States
      • Texas Clinical Research Institute
    • Houston, Texas, United States
      • Ertan Digestive Disease Center of Excellence, UTH/MH-TMC
    • San Antonio, Texas, United States
      • Gastroenterology Research of San Antonio
  • Virginia
    • Chesapeake, Virginia, United States
      • Gastroenterology Associates of Tidewater
    • Norfolk, Virginia, United States
      • Digestive and Liver Disease Specialists
    • Richmond, Virginia, United States
      • McGuire DVAMC
  • Washington
    • Seattle, Washington, United States
      • University of Washington Medical Center

Participation Criteria

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:

• Ability to provide a written informed consent
• Females of childbearing potential must have a negative pregnancy test at screening and baseline
• Documented diagnosis of Crohn's disease with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum
• Moderately to severely active Crohn's disease as defined by a Crohn's Disease Activity Index (CDAI) total score between 220-450 (inclusive) AND with evidence of active disease as measured by ileocolonoscopy

• Within the previous 5 years, demonstrated an inadequate clinical response or intolerance of at least one of the following agents:

  • Corticosteroids
  • Immunomodulators
  • Tumor necrosis factor-alpha (TNFα) antagonists
  • Vedolizumab

• May be receiving the following drugs:

  • Oral 5-aminosalicylate (5-ASA)
  • Oral corticosteroid therapy
  • Antidiarrheals for chronic diarrhea
  • Azathioprine or 6-mercaptopurine (6-MP) or methotrexate
  • Antibiotics for the treatment of Crohn's disease
• Able to comply with the dosing instructions for study drug and able to comply with the study visits and requirements

Key Exclusion Criteria:

• Evidence of abscess at screening
• Extensive colonic resection (subtotal or total colectomy) or history of > 2 small bowel resections
• Ileostomy, colostomy, or symptomatic stenosis of the intestine
• Current use of oral corticosteroids at a dose equivalent to > 30 mg/day of prednisone
• Ulcerative colitis or indeterminate colitis
• Short bowel syndrome
• Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli, Salmonella, Shigella, Campylobacter or Yersinia
• Treatment with any monoclonal antibody within 4 weeks of screening
• History or evidence of colonic mucosal dysplasia
• HIV, hepatitis B, hepatitis C, or tuberculosis (TB) infection
• Participated in a clinical study with an investigational drug or biologic within the last 30 days
• Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the opinion of the investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Andecaliximab 150 mg Every 2 Weeks; Double-Blind Phase: Participants will receive 1 single-use prefilled syringe (PFS) of andecaliximab 150 mg and matching placebo coadministered at Weeks 0, 2, 4, and 6 and 2 single-use PFS of placebo coadministered at Weeks 1, 3, 5, and 7. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.	Drug: Andecaliximab; Andecaliximab administered via subcutaneous (SC) injection; Other Names: GS-5745; Drug: Placebo; Placebo to match andecaliximab administered via SC injection
Experimental: Andecaliximab 150 mg Weekly; Double-Blind Phase: Participants will receive 1 single-use PFS of andecaliximab 150 mg and matching placebo coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.	Drug: Andecaliximab; Andecaliximab administered via subcutaneous (SC) injection; Other Names: GS-5745; Drug: Placebo; Placebo to match andecaliximab administered via SC injection
Experimental: Andecaliximab 300 mg Weekly; Double-Blind Phase: Participants will receive 2 single-use PFS of andecaliximab 150 mg coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for an additional 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.	Drug: Andecaliximab; Andecaliximab administered via subcutaneous (SC) injection; Other Names: GS-5745
Placebo Comparator: Placebo; Double-Blind Phase: Participants will receive 2 single-use PFS of placebo coadministered weekly for 8 weeks. Open-Label Phase: Participants will be eligible to enroll in the Open-Label Phase to receive andecaliximab 150 mg weekly for 44 weeks. Extended Treatment Phase: Participants who complete Week 52 assessments will be eligible to enter into the Extended Treatment Phase to continue treatment with andecaliximab 150 mg for an additional 156 weeks.	Drug: Andecaliximab; Andecaliximab administered via subcutaneous (SC) injection; Other Names: GS-5745; Drug: Placebo; Placebo to match andecaliximab administered via SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Clinical Response (PRO2 Score ≤ 8) at Week 8 of the Double-Blind Phase	Clinical response was defined as patient-reported outcomes (PRO2) score ≤ 8 at Week 8. PRO2 is the weighted average of the 2 variables of frequency of liquid or very soft stool and abdominal pain, based on 7-day participant diary data. The PRO2 score has a minimum score of 0 and has no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with a missing PRO2 value at the Week 8 analysis visit were imputed as not achieving the Clinical Response.	Week 8
Percentage of Participants Achieving Endoscopic Response (≥ 50% Reduction From Baseline SES-CD) at Week 8 of the Double-Blind Phase	Endoscopic response was defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 8. The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing SES-CD value at Week 8 analysis visit were imputed as not achieving Endoscopic Response.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving CDAI Remission (CDAI ≤ 150) at Week 8 of the Double-Blind Phase	Clinical remission was defined as Crohn's Disease Activity Index (CDAI) ≤ 150 at Week 8. CDAI is used as a measure of clinical response and remission. It includes 8 variables of patient-reported symptoms and objective variables: stool count, abdominal pain, general well-being, complications, use of anti-diarrheal medications, presence of abdominal mass, hematocrit values, and weight. It has a minimum range of 0 and no upper bound, with higher scores indicating greater disease activity. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing CDAI score at Week 8 analysis visit were imputed as not achieving CDAI Remission.	Week 8
Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase	The SES-CD evaluates 4 endoscopic variables: ulcer size, ulcerated surface, affected surface, and presence of narrowings. The SES-CD size-of-ulcer subscore ranges from 0 (none) to 3 (very large). Mucosal healing at Week 8 was defined as the size-of-ulcer subscore for segments with non-zero baseline value changes to zero at Week 8 AND the size-of-ulcer subscore for segments with zero value at baseline remain zero at Week 8. Week 8 refers to the analysis window of Day 43 to Day 70 and prior to the first Open-Label dose date. Participants with missing SES-CD size-of-ulcer subscore at Week 8 analysis visit were imputed as not achieving Mucosal Healing.	Week 8

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Team, Gilead Sciences

Publications and helpful links

General Publications

• Schreiber S, Siegel CA, Friedenberg KA, Younes ZH, Seidler U, Bhandari BR, Wang K, Wendt E, McKevitt M, Zhao S, Sundy JS, Lee SD, Loftus EV. A Phase 2, Randomized, Placebo-Controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, in Patients With Moderately to Severely Active Crohn's Disease. J Crohns Colitis. 2018 Aug 29;12(9):1014-1020. doi: 10.1093/ecco-jcc/jjy070.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2015
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): December 22, 2016

Study Registration Dates

• First Submitted: March 27, 2015
• First Submitted That Met QC Criteria: March 27, 2015
• First Posted (Estimate): April 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 11, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: GS-US-395-1663; 2015-001249-10 (EudraCT Number)