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

Sponsor
Takeda (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03943446
Collaborator
Takeda Development Center Americas, Inc. (Industry)
96
Enrollment
43
Locations
3
Arms
29.5
Anticipated Duration (Months)
2.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
96 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
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
Actual Study Start Date :
Aug 14, 2020
Anticipated Primary Completion Date :
Dec 29, 2022
Anticipated Study Completion Date :
Jan 28, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: TAK-018 0.30 g Low Dose

TAK-018 3*0.10 gram (g), tablets, orally, twice daily (BID) for up to 26 weeks.

Drug: TAK-018
TAK-018 immediate-release tablets.
Other Names:
  • Sibofimloc

    		•
    Experimental: TAK-018 1.5 g High Dose

    TAK-018 3*0.50 g, tablets, orally, BID for up to 26 weeks.

    Drug: TAK-018
    TAK-018 immediate-release tablets.
    Other Names:
  • Sibofimloc

    		•
    Placebo Comparator: Placebo

    TAK-018 placebo-matching 3*0 g tablets, orally, BID for up to 26 weeks.

    Drug: TAK-018 Placebo
    TAK-018 placebo-matching tablets.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26 [Week 26]

      Endoscopic recurrence is defined as a Rutgeerts' score greater than or equal to (≥) i2. The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The scale ranges from i0 to i4; where i0 equal to (=) no lesions, i1= less than or equal to (≤) 5 aphthous ulcers, i2= greater than (>) 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.

    Secondary Outcome Measures

    1. Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30 [Weeks 3, 6, 12, 18, 26 and 30]

      Stool samples will be collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity.

    2. Ctrough: Observed Plasma Trough Concentrations of TAK-018 [Week 3 pre-dose and at multiple time points (up to 12 hours) post-dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    2 Cedars-Sinai Medical Center Los Angeles California United States 90048
    3 Hoag Memorial Hospital Presbyterian Los Angeles California United States 92618
    4 University of Colorado Hospital Anschutz Cancer Pavilion Aurora Colorado United States 80045
    5 Mayo Clinic - Jacksonville Jacksonville Florida United States 32224
    6 University of Miami Leonard M. Miller School of Medicine Miami Florida United States 33136
    7 University of South Florida/USF Health Tampa Florida United States 33612
    8 Atlanta Gastroenterology Associates Atlanta Georgia United States 30342
    9 Northwestern University Chicago Illinois United States 60611
    10 The University of Chicago Medical Center Chicago Illinois United States 60637
    11 University of Kentucky Chandler Medical Center Lexington Kentucky United States 40536
    12 Baton Rouge General Medical Center Baton Rouge Louisiana United States 70809
    13 Johns Hopkins University Baltimore Maryland United States 21205
    14 Massachusetts General Hospital Boston Massachusetts United States 02114
    15 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
    16 NYU Langone Inflammatory Bowel Disease Center New York New York United States 10016
    17 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    18 Columbia University Irving Medical Center New York New York United States 10032
    19 University of North Carolina School of Medicine Chapel Hill North Carolina United States 27599-7032
    20 Atrium Health Charlotte North Carolina United States 28204
    21 Cleveland Clinic Cleveland Ohio United States 44195
    22 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213-2536
    23 Vanderbilt Inflammatory Bowel Disease Clinic Nashville Tennessee United States 37212-1375
    24 Houston Methodist Hospital Houston Texas United States 77030-2740
    25 Medizinische Universitat Innsbruck Innsbruck Tyrol Austria 6020
    26 Allgemeines Krankenhaus Wien Wien Vienna Austria 1090
    27 Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre Strasbourg Cedex Alsace France 67200
    28 Centre Hospitalier Universitaire Estaing Clermont-Ferrand Cedex Auvergne France 63003
    29 Hopital Pontchaillou Rennes Cedex 9 Bretagne France 35033
    30 Hopital Saint-Louis Paris Cedex 10 Il-de-France France 75475
    31 Hopital Rangueil Toulouse Cedex 9 Midi-pyrenees France 31059
    32 Centre Hospitalier Universitaire de Nice Hopital l'Archet Nice Cedex 3 Provence Alpes Cote D'Azur France 06202
    33 Universitatsklinikum Freiburg Freiburg Baden-Wuerttemberg Germany 79106
    34 Universitatsmedizin Mannheim Mannheim Baden-Wuerttemberg Germany 68167
    35 Klinikum Luneburg Luneburg Niedersachsen Germany 21339
    36 Evangelisches Krankenhaus Kalk Koln Nordrhein-westfalen Germany 51103
    37 Klinikum Sankt Georg GmbH Leipzig Sachsen Germany 04129
    38 Krankenhaus Waldfriede Berlin Germany 14163
    39 University Hospitals Birmingham NHS Foundation Trust Birmingham England United Kingdom B15 2TH
    40 London North West Healthcare NHS Trust Harrow England United Kingdom HA1 3UJ
    41 University College London Hospitals NHS Foundation Trust London England United Kingdom NWI 2PG
    42 Saint Helens and Knowsley Teaching Hospitals NHS Trust Prescot England United Kingdom L35 5DR
    43 NHS Greater Glasgow and Clyde Glasgow Scotland United Kingdom G51 4TF

    Sponsors and Collaborators

    • Takeda
    • Takeda Development Center Americas, Inc.

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT03943446
    Other Study ID Numbers:
    • TAK-018-2001
    • 2019-000886-19
    • U1111-1225-5064
    • NR266345
    • NL71098.018.19
    First Posted:
    May 9, 2019
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takeda
    Drug Therapy
    Additional relevant MeSH terms:
    Crohn Disease
    Recurrence

    Study Results

    No Results Posted as of Jul 15, 2022