Clinical trial NCT02405442: Safety and Efficacy of Andecaliximab in Participants With Moderately to Severely Active Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-04-01
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Achieving Clinical Response (PRO2 Score ≤ 8) at Week 8 of the Double-Blind Phase
timeFrame: Week 8
measure: Percentage of Participants Achieving Endoscopic Response (≥ 50% Reduction From Baseline SES-CD) at Week 8 of the Double-Blind Phase
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants Achieving CDAI Remission (CDAI ≤ 150) at Week 8 of the Double-Blind Phase
timeFrame: Week 8
measure: Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase
timeFrame: Week 8
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of The Southeast
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Lone Tree
country: United States
facility: South Denver Gastroenterology
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Naples
country: United States
facility: Gastroenterology Group Of Naples
state: Florida
city: Macon
country: United States
facility: Gastroenterology Associates Of Central Georgia, LLC
state: Georgia
city: Indianapolis
country: United States
facility: Medical Diagnostic Center (MDC)-Indiana University (IU) Health University Hospital
state: Indiana
city: Clive
country: United States
facility: Iowa Digestive Disease Center
state: Iowa
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Digestive Health
state: Kansas
city: Monroe
country: United States
facility: Delta Research Partners
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Egg Harbor Township
country: United States
facility: AGA Clinical Research Associates, LLC
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center/ New York Presbyterian
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group Of The Hudson Valley
state: New York
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants For Clinical Research
state: Ohio
city: Mentor
country: United States
facility: Great Lakes Gastroenterology
state: Ohio
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Houston
country: United States
facility: Ertan Digestive Disease Center of Excellence, UTH/MH-TMC
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Research of San Antonio
state: Texas
city: Chesapeake
country: United States
facility: Gastroenterology Associates Of Tidewater
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Richmond
country: United States
facility: Mcguire Dvamc
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Footscray
country: Australia
facility: Footscray Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Gastroenterology/Colorectal Medicine & Genetics
state: Victoria
city: Victoria
country: Canada
facility: Percuro Clinical Research Ltd.
state: British Columbia
city: Victoria
country: Canada
facility: Percuro Clinical Research Ltd.
city: Hradec Kralove 2
country: Czechia
facility: Hepato-Gastroenterologie Hk S.R.O.
city: Praha 7
country: Czechia
facility: Ibd Clinical And Research Centre-Iscare Ivf
city: Clichy Cedex
country: France
facility: Hopital Beaujon
city: Lille
country: France
facility: CHRU de Lille
city: Nantes
country: France
facility: Chu Hotel Dieu-Chu De Nantes
city: Saint Priest en Jarez
country: France
facility: CHU de Saint Etienne - Hopital Nord
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Leipzig
country: Germany
facility: Eugastro Gmbh
city: Muenchen
country: Germany
facility: Klinikum der Universitat Munchen
city: Bekescsaba
country: Hungary
facility: Rethy Pal Hospital-Clinic Bekescsaba
city: Beri Balogh Adam
country: Hungary
facility: Tolna Megye Balassa Janos Korhaz
city: Budapest
country: Hungary
facility: Pannonia Maganorvosi Centrum Kft
city: Debrecen
country: Hungary
facility: Debreceni Egyeterm Orvos es Egeszsegtudomanyi Centrum
city: Roma
country: Italy
facility: Universita Campus Biomedico
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Southern District Health Board
city: Wellington
country: New Zealand
facility: Capital and Coast District Health board-Wellington hospital
city: Bialystok
country: Poland
facility: The Medical University of Bialystok Clinical
city: Lublin
country: Poland
facility: Gastromed
city: Poznan
country: Poland
facility: Ai Centrum Medyczne
city: Poznan
country: Poland
facility: CRC Sp. z o.o.
city: Sopot
country: Poland
facility: Endoskopia SP. z.o.o.
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
city: Wroclaw
country: Poland
facility: Lexmedica
city: Panorama
country: South Africa
facility: Panorama Mediclinic Pvt Hospital
state: Cape Town
city: Durban
country: South Africa
facility: Parklands Medical Centre
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital Nhs Foundation Trust
state: Norfolk
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Team
role: STUDY_DIRECTOR
References:
citation: 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.