A Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery

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

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.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: TAK-018; Drug: TAK-018 Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medizinische Universität Innsbruck
  • Vienna
    • Wien, Vienna, Austria, 1090
      • Allgemeines Krankenhaus Wien
• France
  • Alsace
    • Strasbourg Cedex, Alsace, France, 67200
      • Les Hôpitaux Universitaires de Strasbourg - Hôpital Hautepierre
  • Auvergne
    • Clermont-Ferrand Cedex, Auvergne, France, 63003
      • Centre Hospitalier Universitaire Estaing
  • Bretagne
    • Rennes Cedex 9, Bretagne, France, 35033
      • Hôpital Pontchaillou
  • Il-de-France
    • Paris Cedex 10, Il-de-France, France, 75475
      • Hôpital Saint-Louis
  • Midi-pyrenees
    • Toulouse Cedex 9, Midi-pyrenees, France, 31059
      • Hôpital Rangueil
  • Provence Alpes Cote D'Azur
    • Nice Cedex 3, Provence Alpes Cote D'Azur, France, 06202
      • Centre Hospitalier Universitaire de Nice Hôpital l'Archet
• Germany
  • Berlin, Germany, 14163
    • Krankenhaus Waldfriede
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • Universitätsklinikum Freiburg
    • Mannheim, Baden-Wuerttemberg, Germany, 68167
      • Universitätsmedizin Mannheim
  • Niedersachsen
    • Luneburg, Niedersachsen, Germany, 21339
      • Klinikum Luneburg
  • Nordrhein-westfalen
    • Koln, Nordrhein-westfalen, Germany, 51103
      • Evangelisches Krankenhaus Kalk
  • Sachsen
    • Leipzig, Sachsen, Germany, 04129
      • Klinikum Sankt Georg GmbH
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • University Hospitals Birmingham NHS Foundation Trust
    • Harrow, England, United Kingdom, HA1 3UJ
      • London North West Healthcare NHS Trust
    • Prescot, England, United Kingdom, L35 5DR
      • Saint Helens and Knowsley Teaching Hospitals NHS Trust
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • NHS Greater Glasgow and Clyde
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 92618
      • Hoag Memorial Hospital Presbyterian
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital Anschutz Cancer Pavilion
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Leonard M. Miller School of Medicine
    • Tampa, Florida, United States, 33612
      • University of South Florida/USF Health
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Chandler Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Inflammatory Bowel Disease Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7032
      • University of North Carolina School of Medicine
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-2536
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212-1375
      • Vanderbilt Inflammatory Bowel Disease Clinic
  • Texas
    • Houston, Texas, United States, 77030-2740
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must have a documented diagnosis of CD confirmed by endoscopic biopsy before resection or by tissue obtained at resection.
2. 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.
3. 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.
4. Has resumed oral intake and is capable of swallowing tablets within 72 hours after surgery.

Exclusion Criteria:

1. Has active perianal CD.
2. Has had >3 previous surgical procedures for CD.
3. Has macroscopically active CD that was not resected at the time of surgery as documented in the surgeon's operative report.
4. 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.
5. 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).
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.	Drug: TAK-018 Placebo; TAK-018 placebo-matching tablets.
Experimental: TAK-018 0.30 g Low Dose; TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks.	Drug: TAK-018; TAK-018 immediate-release tablets.; Other Names: Sibofimloc
Experimental: TAK-018 1.5 g High Dose; TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.	Drug: TAK-018; TAK-018 immediate-release tablets.; Other Names: Sibofimloc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Weeks 3, 6, 12, 18, 26 and 30
Ctrough: Observed Plasma Trough Concentrations of TAK-018		Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): August 25, 2022
• Study Completion (Actual): August 25, 2022

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Recurrence; Crohn Disease
• Other Study ID Numbers: TAK-018-2001; 2019-000886-19 (EudraCT Number); U1111-1225-5064 (Registry Identifier: WHO); NR266345 (Registry Identifier: IRAS); NL71098.018.19 (Registry Identifier: CCMO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No