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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02405442
• Other study ID #: GS-US-395-1663
• Secondary ID: 2015-001249-10
• Status: Terminated
• Phase: Phase 2
• Start date: April 30, 2015
• Est. completion date: December 22, 2016

Study information

• Verified date: April 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 187
• Est. completion date: December 22, 2016
• Est. primary completion date: November 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (TNFa) 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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Andecaliximab
Andecaliximab administered via subcutaneous (SC) injection
• Placebo
Placebo to match andecaliximab administered via SC injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  New Zealand,  Poland,  South Africa,  Spain,  United Kingdom, 

References & 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 Jr. A phase 2, Randomized, Placebo-controlled Study Evaluating Matrix Metalloproteinase-9 Inhibitor, Andecaliximab, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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