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

NCT03943446 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: TAK-018-20012019-000886-19U1111-1225-5064NR266345NL71098.018.19
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 41

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.

Conditions

Crohn Disease

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

• Ctrough: Observed Plasma Trough Concentrations of TAK-018

  Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3

Study Arms (3)

Placebo

PLACEBO COMPARATOR

TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.

Drug: TAK-018 Placebo

TAK-018 0.30 g Low Dose

EXPERIMENTAL

TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks.

Drug: TAK-018

TAK-018 1.5 g High Dose

EXPERIMENTAL

TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.

Drug: TAK-018

Interventions

TAK-018 DRUG

TAK-018 immediate-release tablets.

Also known as: Sibofimloc

TAK-018 0.30 g Low Dose; TAK-018 1.5 g High Dose

TAK-018 Placebo DRUG

TAK-018 placebo-matching tablets.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (41)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Hoag Memorial Hospital Presbyterian

Los Angeles, California, 92618, United States

Location

University of Colorado Hospital Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami Leonard M. Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida/USF Health

Tampa, Florida, 33612, United States

Location

Atlanta Gastroenterology Associates

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

NYU Langone Inflammatory Bowel Disease Center

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599-7032, United States

Location

Atrium Health

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213-2536, United States

Location

Vanderbilt Inflammatory Bowel Disease Clinic

Nashville, Tennessee, 37212-1375, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030-2740, United States

Location

Medizinische Universitat Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Allgemeines Krankenhaus Wien

Vienna, Vienna, 1090, Austria

Location

Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre

Strasbourg, Alsace, 67200, France

Location

Centre Hospitalier Universitaire Estaing

Clermont-Ferrand, Auvergne, 63003, France

Location

Hopital Pontchaillou

Rennes, Brittany Region, 35033, France

Location

Hopital Saint-Louis

Paris, Il-de-France, 75475, France

Location

Hopital Rangueil

Toulouse, Midi-pyrenees, 31059, France

Location

Centre Hospitalier Universitaire de Nice Hopital l'Archet

Nice, Provence-Alpes-Côte d'Azur Region, 06202, France

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitatsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Klinikum Luneburg

Lüneburg, Lower Saxony, 21339, Germany

Location

Evangelisches Krankenhaus Kalk

Cologne, North Rhine-Westphalia, 51103, Germany

Location

Klinikum Sankt Georg GmbH

Leipzig, Saxony, 04129, Germany

Location

Krankenhaus Waldfriede

Berlin, 14163, Germany

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, England, B15 2TH, United Kingdom

Location

London North West Healthcare NHS Trust

Harrow, England, HA1 3UJ, United Kingdom

Location

Saint Helens and Knowsley Teaching Hospitals NHS Trust

Prescot, England, L35 5DR, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G51 4TF, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

This study is terminated as the sponsor decided to discontinue study due to inability to recruit the expected number of participants within the requisite time period.

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 9, 2019
• Study Start: August 4, 2020
• Primary Completion: August 25, 2022
• Study Completion: August 25, 2022
• Last Updated: September 7, 2023
• Results First Posted: September 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

GB (4); US (23); FR (6); DE (6); AU (2)