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

NCT02405442 | Terminated Phase 2 Results DMC

• 2 other identifiers: GS-US-395-16632015-001249-10
• Study Type: interventional
• Target: 187
• Locations: 13 countries
• Sites: 74

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.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Percentage of Participants Achieving CDAI Remission (CDAI ≤ 150) at Week 8 of the Double-Blind Phase

  Week 8

• Percentage of Participants Achieving Mucosal Healing (SES-CD Size-of-Ulcer Subscore = 0) at Week 8 of the Double-Blind Phase

  Week 8

Study Arms (4)

Andecaliximab 150 mg Every 2 Weeks

EXPERIMENTAL

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; Drug: Placebo

Andecaliximab 150 mg Weekly

EXPERIMENTAL

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; Drug: Placebo

Andecaliximab 300 mg Weekly

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Andecaliximab DRUG

Andecaliximab administered via subcutaneous (SC) injection

Also known as: GS-5745

Andecaliximab 150 mg Every 2 Weeks; Andecaliximab 150 mg Weekly; Andecaliximab 300 mg Weekly; Placebo

Placebo DRUG

Placebo to match andecaliximab administered via SC injection

Andecaliximab 150 mg Every 2 Weeks; Andecaliximab 150 mg Weekly; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (74)

Digestive Health Specialists of The Southeast

Dothan, Alabama, United States

Location

Mayo Clinic

Scottsdale, Arizona, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, United States

Location

South Denver Gastroenterology

Lone Tree, Colorado, United States

Location

University of Miami

Miami, Florida, United States

Location

Gastroenterology Group Of Naples

Naples, Florida, United States

Location

Gastroenterology Associates Of Central Georgia, LLC

Macon, Georgia, United States

Location

Medical Diagnostic Center (MDC)-Indiana University (IU) Health University Hospital

Indianapolis, Indiana, United States

Location

Iowa Digestive Disease Center

Clive, Iowa, United States

Location

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, United States

Location

Delta Research Partners

Monroe, Louisiana, United States

Location

Louisiana Research Center

Shreveport, Louisiana, United States

Location

University of Michigan

Ann Arbor, Michigan, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, United States

Location

Washington University School of Medicine

St Louis, Missouri, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Location

AGA Clinical Research Associates, LLC

Egg Harbor, New Jersey, United States

Location

Columbia University Medical Center/ New York Presbyterian

New York, New York, United States

Location

Premier Medical Group Of The Hudson Valley

Poughkeepsie, New York, United States

Location

Mayo Clinic Rochester

Rochester, New York, United States

Location

Asheville Gastroenterology Associates

Asheville, North Carolina, United States

Location

Consultants For Clinical Research

Cincinnati, Ohio, United States

Location

Great Lakes Gastroenterology

Mentor, Ohio, United States

Location

Gastro One

Germantown, Tennessee, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

Texas Clinical Research Institute

Arlington, Texas, United States

Location

Ertan Digestive Disease Center of Excellence, UTH/MH-TMC

Houston, Texas, United States

Location

Gastroenterology Research of San Antonio

San Antonio, Texas, United States

Location

Gastroenterology Associates Of Tidewater

Chesapeake, Virginia, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, United States

Location

Mcguire Dvamc

Richmond, Virginia, United States

Location

University of Washington Medical Center

Seattle, Washington, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, Australia

Location

Footscray Hospital

Footscray, Victoria, Australia

Location

Gastroenterology/Colorectal Medicine & Genetics

Melbourne, Victoria, Australia

Location

Percuro Clinical Research Ltd.

Victoria, British Columbia, Canada

Location

Percuro Clinical Research Ltd.

Victoria, Canada

Location

Hepato-Gastroenterologie Hk S.R.O.

Hradec Králové, Czechia

Location

Ibd Clinical And Research Centre-Iscare Ivf

Prague, Czechia

Location

Hopital Beaujon

Clichy, France

Location

CHRU de Lille

Lille, France

Location

Chu Hotel Dieu-Chu De Nantes

Nantes, France

Location

CHU de Saint Etienne - Hopital Nord

Saint-Priest-en-Jarez, France

Location

Universitatsklinikum Schleswig-Holstein

Kiel, Germany

Location

Eugastro Gmbh

Leipzig, Germany

Location

Klinikum der Universitat Munchen

München, Germany

Location

Tolna Megye Balassa Janos Korhaz

Beri Balogh Adam, Hungary

Location

Rethy Pal Hospital-Clinic Bekescsaba

Békéscsaba, Hungary

Location

Pannonia Maganorvosi Centrum Kft

Budapest, Hungary

Location

Debreceni Egyeterm Orvos es Egeszsegtudomanyi Centrum

Debrecen, Hungary

Location

Universita Campus Biomedico

Roma, Italy

Location

Humanitas Research Hospital

Rozzano, Italy

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Southern District Health Board

Dunedin, New Zealand

Location

Capital and Coast District Health board-Wellington hospital

Wellington, New Zealand

Location

The Medical University of Bialystok Clinical

Bialystok, Poland

Location

Gastromed

Lublin, Poland

Location

Ai Centrum Medyczne

Poznan, Poland

Location

CRC Sp. z o.o.

Poznan, Poland

Location

Endoskopia SP. z.o.o.

Sopot, Poland

Location

Centralny Szpital Kliniczny MSWiA

Warsaw, Poland

Location

Lexmedica

Wroclaw, Poland

Location

Panorama Mediclinic Pvt Hospital

Panorama, Cape Town, South Africa

Location

Parklands Medical Centre

Durban, South Africa

Location

Hospital Universitari de Bellvitge

Barcelona, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain

Location

Norfolk and Norwich University Hospital Nhs Foundation Trust

Norwich, Norfolk, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29846530 RESULT

MeSH Terms

Conditions

Crohn Disease

Interventions

andecaliximab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

A prespecified topline analysis was performed after the last enrolled subject received the 8-week Double-Blind induction treatment. Based on this review, Gilead terminated the Open-Label and Extended Treatment Phases of study due to lack of efficacy.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Team

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2015
• First Posted: April 1, 2015
• Study Start: April 30, 2015
• Primary Completion: November 30, 2016
• Study Completion: December 22, 2016
• Last Updated: April 23, 2019
• Results First Posted: March 28, 2019

Record last verified: 2019-04

Locations

US (33); FR (4); HU (4); CA (2); NZ (3); PL (7); ZA (2); ES (4); AU (5); GB (3); DE (3); IT (2); CZ (2)