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

Phase 2

Terminated

Conditions: Crohn's Disease

Interventions: Drug: Andecaliximab
Drug: Placebo

Registration Number: NCT02405442

Lead Sponsor: Gilead Sciences

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 187

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Andecaliximab 150 mg Every 2 Weeks	Placebo	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.
Andecaliximab 300 mg Weekly	Andecaliximab	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.
Placebo	Andecaliximab	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.
Placebo	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.
Andecaliximab 150 mg Weekly	Placebo	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.
Andecaliximab 150 mg Every 2 Weeks	Andecaliximab	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.
Andecaliximab 150 mg Weekly	Andecaliximab	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Clinical Response (PRO2 Score ≤ 8) at Week 8 of the Double-Blind Phase	Week 8	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.
Percentage of Participants Achieving Endoscopic Response (≥ 50% Reduction From Baseline SES-CD) at Week 8 of the Double-Blind Phase	Week 8	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving CDAI Remission (CDAI ≤ 150) at Week 8 of the Double-Blind Phase	Week 8	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.
Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase	Week 8	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.

Trial Locations

Locations (72): Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
University of Miami
🇺🇸
Miami, Florida, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Cotton-O'Neil Clinical Research Center, Digestive Health
🇺🇸
Topeka, Kansas, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Debreceni Egyeterm Orvos es Egeszsegtudomanyi Centrum
🇭🇺
Debrecen, Hungary
Dartmouth-Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Gastromed
🇵🇱
Lublin, Poland
CRC Sp. z o.o.
🇵🇱
Poznan, Poland
Lexmedica
🇵🇱
Wroclaw, Poland
Consultants For Clinical Research
🇺🇸
Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Oxford University Hospitals NHS Trust
🇬🇧
Oxford, United Kingdom
Gastroenterology Associates Of Central Georgia, LLC
🇺🇸
Macon, Georgia, United States
Mayo Clinic Rochester
🇺🇸
Rochester, New York, United States
Louisiana Research Center
🇺🇸
Shreveport, Louisiana, United States
Delta Research Partners
🇺🇸
Monroe, Louisiana, United States
Clinical Research Institute of Michigan, LLC
🇺🇸
Chesterfield, Michigan, United States
Columbia University Medical Center/ New York Presbyterian
🇺🇸
New York, New York, United States
Asheville Gastroenterology Associates
🇺🇸
Asheville, North Carolina, United States
AGA Clinical Research Associates, LLC
🇺🇸
Egg Harbor Township, New Jersey, United States
Gastro One
🇺🇸
Germantown, Tennessee, United States
Gastroenterology Research of San Antonio
🇺🇸
San Antonio, Texas, United States
Texas Clinical Research Institute
🇺🇸
Arlington, Texas, United States
Hopital Beaujon
🇫🇷
Clichy Cedex, France
CHRU de Lille
🇫🇷
Lille, France
Klinikum der Universitat Munchen
🇩🇪
Muenchen, Germany
Eugastro Gmbh
🇩🇪
Leipzig, Germany
Rethy Pal Hospital-Clinic Bekescsaba
🇭🇺
Bekescsaba, Hungary
Universita Campus Biomedico
🇮🇹
Roma, Italy
Christchurch Hospital
🇳🇿
Christchurch, New Zealand
Capital and Coast District Health board-Wellington hospital
🇳🇿
Wellington, New Zealand
South Denver Gastroenterology
🇺🇸
Lone Tree, Colorado, United States
Digestive Health Specialists of The Southeast
🇺🇸
Dothan, Alabama, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Gastroenterology Group Of Naples
🇺🇸
Naples, Florida, United States
Medical Diagnostic Center (MDC)-Indiana University (IU) Health University Hospital
🇺🇸
Indianapolis, Indiana, United States
Iowa Digestive Disease Center
🇺🇸
Clive, Iowa, United States
Premier Medical Group Of The Hudson Valley
🇺🇸
Poughkeepsie, New York, United States
Great Lakes Gastroenterology
🇺🇸
Mentor, Ohio, United States
Ertan Digestive Disease Center of Excellence, UTH/MH-TMC
🇺🇸
Houston, Texas, United States
Gastroenterology Associates Of Tidewater
🇺🇸
Chesapeake, Virginia, United States
Digestive and Liver Disease Specialists
🇺🇸
Norfolk, Virginia, United States
Mcguire Dvamc
🇺🇸
Richmond, Virginia, United States
Concord Repatriation General Hospital
🇦🇺
Concord, New South Wales, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
Footscray Hospital
🇦🇺
Footscray, Victoria, Australia
Hepato-Gastroenterologie Hk S.R.O.
🇨🇿
Hradec Kralove 2, Czechia
Gastroenterology/Colorectal Medicine & Genetics
🇦🇺
Melbourne, Victoria, Australia
Percuro Clinical Research Ltd.
🇨🇦
Victoria, Canada
Ibd Clinical And Research Centre-Iscare Ivf
🇨🇿
Praha 7, Czechia
Chu Hotel Dieu-Chu De Nantes
🇫🇷
Nantes, France
CHU de Saint Etienne - Hopital Nord
🇫🇷
Saint Priest en Jarez, France
Universitatsklinikum Schleswig-Holstein
🇩🇪
Kiel, Germany
Tolna Megye Balassa Janos Korhaz
🇭🇺
Beri Balogh Adam, Hungary
Pannonia Maganorvosi Centrum Kft
🇭🇺
Budapest, Hungary
Humanitas Research Hospital
🇮🇹
Rozzano, Italy
Southern District Health Board
🇳🇿
Dunedin, New Zealand
The Medical University of Bialystok Clinical
🇵🇱
Bialystok, Poland
Ai Centrum Medyczne
🇵🇱
Poznan, Poland
Centralny Szpital Kliniczny MSWiA
🇵🇱
Warszawa, Poland
Endoskopia SP. z.o.o.
🇵🇱
Sopot, Poland
Panorama Mediclinic Pvt Hospital
🇿🇦
Panorama, Cape Town, South Africa
Parklands Medical Centre
🇿🇦
Durban, South Africa
Hospital Universitari de Bellvitge
🇪🇸
Barcelona, Spain
Hospital Universitario de Fuenlabrada
🇪🇸
Fuenlabrada, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Hospital Ramon y Cajal
🇪🇸
Madrid, Spain
Norfolk and Norwich University Hospital Nhs Foundation Trust
🇬🇧
Norwich, Norfolk, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧
Cambridge, United Kingdom
Mayo Clinic
🇺🇸
Scottsdale, Arizona, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States