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

Crohn Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03943446
• Other study ID #: TAK-018-2001
• Secondary ID: 2019-000886-19U1
• Status: Terminated
• Phase: Phase 2
• Start date: August 4, 2020
• Est. completion date: August 25, 2022

Study information

• Verified date: August 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: August 25, 2022
• Est. primary completion date: August 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-a) 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.

Related Conditions & MeSH terms

• Crohn Disease
• Recurrence

Intervention

Drug:
• TAK-018
TAK-018 immediate-release tablets.
• TAK-018 Placebo
TAK-018 placebo-matching tablets.

Locations

Country	Name	City	State
Austria	Medizinische Universitat Innsbruck	Innsbruck	Tyrol
Austria	Allgemeines Krankenhaus Wien	Wien	Vienna
France	Centre Hospitalier Universitaire Estaing	Clermont-Ferrand Cedex	Auvergne
France	Centre Hospitalier Universitaire de Nice Hopital l'Archet	Nice Cedex 3	Provence Alpes Cote D'Azur
France	Hopital Saint-Louis	Paris Cedex 10	Il-de-France
France	Hopital Pontchaillou	Rennes Cedex 9	Bretagne
France	Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre	Strasbourg Cedex	Alsace
France	Hopital Rangueil	Toulouse Cedex 9	Midi-pyrenees
Germany	Krankenhaus Waldfriede	Berlin
Germany	Universitatsklinikum Freiburg	Freiburg	Baden-Wuerttemberg
Germany	Evangelisches Krankenhaus Kalk	Koln	Nordrhein-westfalen
Germany	Klinikum Sankt Georg GmbH	Leipzig	Sachsen
Germany	Klinikum Luneburg	Luneburg	Niedersachsen
Germany	Universitatsmedizin Mannheim	Mannheim	Baden-Wuerttemberg
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	England
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow	Scotland
United Kingdom	London North West Healthcare NHS Trust	Harrow	England
United Kingdom	Saint Helens and Knowsley Teaching Hospitals NHS Trust	Prescot	England
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	University of Colorado Hospital Anschutz Cancer Pavilion	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Atrium Health	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Houston Methodist Hospital	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Hoag Memorial Hospital Presbyterian	Los Angeles	California
United States	University of Miami Leonard M. Miller School of Medicine	Miami	Florida
United States	Vanderbilt Inflammatory Bowel Disease Clinic	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Inflammatory Bowel Disease Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of South Florida/USF Health	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Ctrough: Observed Plasma Trough Concentrations of TAK-018		Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3

External Links

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