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

Phase 2

Terminated

• Conditions: Crohn Disease
• Interventions: Drug: TAK-018 Placebo; Drug: TAK-018

• Registration Number: NCT03943446
• Lead Sponsor: Takeda

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.

Study Timeline

• Study First Submitted: 2019-05-07
• Study First Submitted QC: 2019-05-07
• Study First Posted: 2019-05-09
• Study Start: 2020-08-04
• Primary Completion: 2022-08-25
• Study Completion: 2022-08-25
• Status Verified: 2023-08
• Results First Submitted: 2023-08-11
• Results First Submitted QC: 2023-08-11
• Last Update Submitted: 2023-08-11
• Results First Posted: 2023-09-07
• Last Update Posted: 2023-09-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	TAK-018 Placebo	TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.
TAK-018 0.30 g Low Dose	TAK-018	TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks.
TAK-018 1.5 g High Dose	TAK-018	TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26	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

Name	Time	Method
Ctrough: Observed Plasma Trough Concentrations of TAK-018	Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30	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.

Trial Locations

Locations (41)

Hopital Saint-Louis; 🇫🇷 Paris Cedex 10, Il-de-France, France

Centre Hospitalier Universitaire de Nice Hopital l'Archet; 🇫🇷 Nice Cedex 3, Provence Alpes Cote D'Azur, France

University of Kentucky Chandler Medical Center; 🇺🇸 Lexington, Kentucky, United States

University of South Florida/USF Health; 🇺🇸 Tampa, Florida, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

Atrium Health; 🇺🇸 Charlotte, North Carolina, United States

University of Colorado Hospital Anschutz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

NYU Langone Inflammatory Bowel Disease Center; 🇺🇸 New York, New York, United States

Atlanta Gastroenterology Associates; 🇺🇸 Atlanta, Georgia, United States

Mayo Clinic - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

The University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Centre Hospitalier Universitaire Estaing; 🇫🇷 Clermont-Ferrand Cedex, Auvergne, France

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Universitatsklinikum Freiburg; 🇩🇪 Freiburg, Baden-Wuerttemberg, Germany

Hopital Rangueil; 🇫🇷 Toulouse Cedex 9, Midi-pyrenees, France

Klinikum Luneburg; 🇩🇪 Luneburg, Niedersachsen, Germany

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Universitatsmedizin Mannheim; 🇩🇪 Mannheim, Baden-Wuerttemberg, Germany

Krankenhaus Waldfriede; 🇩🇪 Berlin, Germany

Evangelisches Krankenhaus Kalk; 🇩🇪 Koln, Nordrhein-westfalen, Germany

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Allgemeines Krankenhaus Wien; 🇦🇹 Wien, Vienna, Austria

Klinikum Sankt Georg GmbH; 🇩🇪 Leipzig, Sachsen, Germany

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, England, United Kingdom

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Medizinische Universitat Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Hopital Pontchaillou; 🇫🇷 Rennes Cedex 9, Bretagne, France

London North West Healthcare NHS Trust; 🇬🇧 Harrow, England, United Kingdom

Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre; 🇫🇷 Strasbourg Cedex, Alsace, France

Vanderbilt Inflammatory Bowel Disease Clinic; 🇺🇸 Nashville, Tennessee, United States

NHS Greater Glasgow and Clyde; 🇬🇧 Glasgow, Scotland, United Kingdom

Saint Helens and Knowsley Teaching Hospitals NHS Trust; 🇬🇧 Prescot, England, United Kingdom

Hoag Memorial Hospital Presbyterian; 🇺🇸 Los Angeles, California, United States

University of Miami Leonard M. Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of North Carolina School of Medicine; 🇺🇸 Chapel Hill, North Carolina, United States