Back to resultsA Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery
Primary Purpose
Crohn Disease
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TAK-018
TAK-018 Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Crohn Disease focused on measuring Drug Therapy
Eligibility Criteria
Inclusion Criteria:
- Must have a documented diagnosis of CD confirmed by endoscopic biopsy before resection or by tissue obtained at resection.
- Planned to undergo a laparoscopic ileocecal resection with primary anastomosis within 72 hours before randomization Day 1. Confirmation that no active disease has been left behind after resection will be based on surgeon's documentation in the operative report.
- With postoperative discontinuation of all concomitant medications specifically related to the treatment of CD. This includes anti-tumor necrosis factor-alpha (TNF-α) and anti-integrin therapy, anti- interleukin (IL) 12/23, thiopurines and other immunomodulators, steroids, 5-minosalicylates, and prophylactic use of antibiotics for the prevention of postoperative recurrence such as metronidazole.
- Has resumed oral intake and is capable of swallowing tablets within 72 hours after surgery.
Exclusion Criteria:
- Has active perianal CD.
- Has had >3 previous surgical procedures for CD.
- Has macroscopically active CD that was not resected at the time of surgery as documented in the surgeon's operative report.
- With small bowel resection that exceeds 100 centimeter (cm) or a participant who is considered at risk of short bowel syndrome by the surgeon or investigator.
- Has active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following: history of tuberculosis, OR positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR a tuberculin skin test reaction ≥10 millimeter (mm) (≥5 mm in participants receiving the equivalent of >15 milligram per day (mg/day) prednisone).
- Has chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen) or hepatitis C infection (evident by viral replication by polymerase chain reaction) within 30 days of randomization.
Sites / Locations
- University of Arkansas for Medical Sciences
- Cedars-Sinai Medical Center
- Hoag Memorial Hospital Presbyterian
- University of Colorado Hospital Anschutz Cancer Pavilion
- Mayo Clinic - Jacksonville
- University of Miami Leonard M. Miller School of Medicine
- University of South Florida/USF Health
- Atlanta Gastroenterology Associates
- Northwestern University
- The University of Chicago Medical Center
- University of Kentucky Chandler Medical Center
- Johns Hopkins University
- Massachusetts General Hospital
- Dartmouth-Hitchcock Medical Center
- NYU Langone Inflammatory Bowel Disease Center
- Icahn School of Medicine at Mount Sinai
- Columbia University Irving Medical Center
- University of North Carolina School of Medicine
- Atrium Health
- Cleveland Clinic
- University of Pittsburgh Medical Center
- Vanderbilt Inflammatory Bowel Disease Clinic
- Houston Methodist Hospital
- Medizinische Universitat Innsbruck
- Allgemeines Krankenhaus Wien
- Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre
- Centre Hospitalier Universitaire Estaing
- Hopital Pontchaillou
- Hopital Saint-Louis
- Hopital Rangueil
- Centre Hospitalier Universitaire de Nice Hopital l'Archet
- Universitatsklinikum Freiburg
- Universitatsmedizin Mannheim
- Klinikum Luneburg
- Evangelisches Krankenhaus Kalk
- Klinikum Sankt Georg GmbH
- Krankenhaus Waldfriede
- University Hospitals Birmingham NHS Foundation Trust
- London North West Healthcare NHS Trust
- Saint Helens and Knowsley Teaching Hospitals NHS Trust
- NHS Greater Glasgow and Clyde
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
TAK-018 0.30 g Low Dose
TAK-018 1.5 g High Dose
Arm Description
TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.
TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks.
TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26
Endoscopic recurrence (ER) is defined as a Rutgeerts' score ≥ i2. The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The total score ranges from i0 to i4; where i0 = no lesions, i1= ≤ 5 aphthous ulcers, i2= > 5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis, i3= diffuse aphthous ileitis with diffusely inflamed mucosa and i4= diffuse inflammation with larger ulcers, nodules, and/or narrowing. Higher score indicates worsening. Percentages are rounded off to the nearest single decimal.
Secondary Outcome Measures
Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30
Stool samples were collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity. Percentages are rounded off to the nearest single decimal.
Ctrough: Observed Plasma Trough Concentrations of TAK-018
Full Information
NCT ID
NCT03943446
First Posted
May 7, 2019
Last Updated
August 11, 2023
Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03943446
Brief Title
A Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2a Study to Evaluate the Safety, Tolerability, and Early Proof of Concept of TAK-018 for the Prevention of Postoperative Crohn's Disease Recurrence
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision to discontinue study due to inability to recruit the expected number of subjects within the requisite time period.
Study Start Date
August 4, 2020 (Actual)
Primary Completion Date
August 25, 2022 (Actual)
Study Completion Date
August 25, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The main aim is to see if TAK-018 reduces the recurrence of intestinal inflammation after abdominal resection surgery in adults with Crohn's disease.
Participants will take either TAK-018 or placebo tablets by mouth, 2 times each day for up to 26 weeks after surgery. The placebo looks like TAK-018 but will not have any medicine in it.
Participants will have 6 study visits while receiving treatment. Visits 1 and 6 will be conducted at the study clinic. The others can be in the clinic or at the participant's home. Follow-up will occur 4 weeks after final treatment.
Detailed Description
The drug being tested in this study is called TAK-018 (Sibofimloc). TAK-018 is used for the prevention of postoperative CD recurrence. This study will evaluate the efficacy of TAK-018 in reducing endoscopic recurrence of intestinal inflammation in postoperative participants with CD after planned laparoscopic ileocecal resection with primary anastomosis.
The study will enroll approximately 96 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 1:1:1 ratio to one of the three treatment groups-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need):
TAK-018 0.30 g Low dose
TAK-018 1.5 g High dose
Placebo
All participants will be asked to take the tablets twice daily immediately after a meal (that is, breakfast and dinner) with water, approximately 8 to 12 hours apart.
Participants will have flexibility to either to opt for home health care (HHC) solutions at Screening, Week 3, Week 6, Week 12, Week 18 and Week 30 or travel to the clinic for all scheduled visits per protocol as permitted by local regulations. This flexible approach is designed in response to health care delivery challenges presented by the coronavirus disease (COVID-19) pandemic and to provide additional flexibility during the course of the trial. Assessments after surgery and endoscopy at Week 26 will be conducted at the clinic. All other study visits may be conducted by telehealth and home health care (HHC).
This multi-center trial will be conducted in the United States, United Kingdom, France, Austria and Germany. The overall time to participate in this study is approximately 34 weeks. Participants will make final visit to the clinic or can opt for HHC visit at Week 30 (30 days after the Week 26 endoscopy) for safety follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Drug Therapy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.
Arm Title
TAK-018 0.30 g Low Dose
Arm Type
Experimental
Arm Description
TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks.
Arm Title
TAK-018 1.5 g High Dose
Arm Type
Experimental
Arm Description
TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Intervention Type
Drug
Intervention Name(s)
TAK-018
Other Intervention Name(s)
Sibofimloc
Intervention Description
TAK-018 immediate-release tablets.
Intervention Type
Drug
Intervention Name(s)
TAK-018 Placebo
Intervention Description
TAK-018 placebo-matching tablets.
Primary Outcome Measure Information:
Title
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26
Description
Endoscopic recurrence (ER) is defined as a Rutgeerts' score ≥ i2. The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The total score ranges from i0 to i4; where i0 = no lesions, i1= ≤ 5 aphthous ulcers, i2= > 5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis, i3= diffuse aphthous ileitis with diffusely inflamed mucosa and i4= diffuse inflammation with larger ulcers, nodules, and/or narrowing. Higher score indicates worsening. Percentages are rounded off to the nearest single decimal.
Time Frame
At Week 26
Secondary Outcome Measure Information:
Title
Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30
Description
Stool samples were collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity. Percentages are rounded off to the nearest single decimal.
Time Frame
At Weeks 3, 6, 12, 18, 26 and 30
Title
Ctrough: Observed Plasma Trough Concentrations of TAK-018
Time Frame
Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a documented diagnosis of CD confirmed by endoscopic biopsy before resection or by tissue obtained at resection.
Planned to undergo a laparoscopic ileocecal resection with primary anastomosis within 72 hours before randomization Day 1. Confirmation that no active disease has been left behind after resection will be based on surgeon's documentation in the operative report.
With postoperative discontinuation of all concomitant medications specifically related to the treatment of CD. This includes anti-tumor necrosis factor-alpha (TNF-α) and anti-integrin therapy, anti- interleukin (IL) 12/23, thiopurines and other immunomodulators, steroids, 5-minosalicylates, and prophylactic use of antibiotics for the prevention of postoperative recurrence such as metronidazole.
Has resumed oral intake and is capable of swallowing tablets within 72 hours after surgery.
Exclusion Criteria:
Has active perianal CD.
Has had >3 previous surgical procedures for CD.
Has macroscopically active CD that was not resected at the time of surgery as documented in the surgeon's operative report.
With small bowel resection that exceeds 100 centimeter (cm) or a participant who is considered at risk of short bowel syndrome by the surgeon or investigator.
Has active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following: history of tuberculosis, OR positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR a tuberculin skin test reaction ≥10 millimeter (mm) (≥5 mm in participants receiving the equivalent of >15 milligram per day (mg/day) prednisone).
Has chronic hepatitis B (hepatitis B surface antigen positive, or positive for both hepatitis B surface antibody and hepatitis B core antibody but negative for hepatitis B surface antigen) or hepatitis C infection (evident by viral replication by polymerase chain reaction) within 30 days of randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Hoag Memorial Hospital Presbyterian
City
Los Angeles
State/Province
California
ZIP/Postal Code
92618
Country
United States
Facility Name
University of Colorado Hospital Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mayo Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Miami Leonard M. Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida/USF Health
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Atlanta Gastroenterology Associates
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Kentucky Chandler Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
NYU Langone Inflammatory Bowel Disease Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina School of Medicine
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7032
Country
United States
Facility Name
Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-2536
Country
United States
Facility Name
Vanderbilt Inflammatory Bowel Disease Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212-1375
Country
United States
Facility Name
Houston Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2740
Country
United States
Facility Name
Medizinische Universitat Innsbruck
City
Innsbruck
State/Province
Tyrol
ZIP/Postal Code
6020
Country
Austria
Facility Name
Allgemeines Krankenhaus Wien
City
Wien
State/Province
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre
City
Strasbourg Cedex
State/Province
Alsace
ZIP/Postal Code
67200
Country
France
Facility Name
Centre Hospitalier Universitaire Estaing
City
Clermont-Ferrand Cedex
State/Province
Auvergne
ZIP/Postal Code
63003
Country
France
Facility Name
Hopital Pontchaillou
City
Rennes Cedex 9
State/Province
Bretagne
ZIP/Postal Code
35033
Country
France
Facility Name
Hopital Saint-Louis
City
Paris Cedex 10
State/Province
Il-de-France
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Rangueil
City
Toulouse Cedex 9
State/Province
Midi-pyrenees
ZIP/Postal Code
31059
Country
France
Facility Name
Centre Hospitalier Universitaire de Nice Hopital l'Archet
City
Nice Cedex 3
State/Province
Provence Alpes Cote D'Azur
ZIP/Postal Code
06202
Country
France
Facility Name
Universitatsklinikum Freiburg
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitatsmedizin Mannheim
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68167
Country
Germany
Facility Name
Klinikum Luneburg
City
Luneburg
State/Province
Niedersachsen
ZIP/Postal Code
21339
Country
Germany
Facility Name
Evangelisches Krankenhaus Kalk
City
Koln
State/Province
Nordrhein-westfalen
ZIP/Postal Code
51103
Country
Germany
Facility Name
Klinikum Sankt Georg GmbH
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04129
Country
Germany
Facility Name
Krankenhaus Waldfriede
City
Berlin
ZIP/Postal Code
14163
Country
Germany
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
London North West Healthcare NHS Trust
City
Harrow
State/Province
England
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Saint Helens and Knowsley Teaching Hospitals NHS Trust
City
Prescot
State/Province
England
ZIP/Postal Code
L35 5DR
Country
United Kingdom
Facility Name
NHS Greater Glasgow and Clyde
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G51 4TF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b603b4db2bf003ab4a2e7
Description
To obtain more information about this study, click this link.
Learn more about this trial
A Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery
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