Clinical trial NCT03943446: A Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2019-05-09
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26
timeFrame: At Week 26
Secondary outcomes:
measure: Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30
timeFrame: At Weeks 3, 6, 12, 18, 26 and 30
measure: Ctrough: Observed Plasma Trough Concentrations of TAK-018
timeFrame: Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital Anschutz Cancer Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Leonard M. Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida/USF Health
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: NYU Langone Inflammatory Bowel Disease Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina School of Medicine
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Inflammatory Bowel Disease Clinic
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
state: Tyrol
city: Wien
country: Austria
facility: Allgemeines Krankenhaus Wien
state: Vienna
city: Strasbourg Cedex
country: France
facility: Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre
state: Alsace
city: Clermont-Ferrand Cedex
country: France
facility: Centre Hospitalier Universitaire Estaing
state: Auvergne
city: Rennes Cedex 9
country: France
facility: Hopital Pontchaillou
state: Bretagne
city: Paris Cedex 10
country: France
facility: Hopital Saint-Louis
state: Il-de-France
city: Toulouse Cedex 9
country: France
facility: Hopital Rangueil
state: Midi-pyrenees
city: Nice Cedex 3
country: France
facility: Centre Hospitalier Universitaire de Nice Hopital l'Archet
state: Provence Alpes Cote D'Azur
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: Universitatsmedizin Mannheim
state: Baden-Wuerttemberg
city: Luneburg
country: Germany
facility: Klinikum Luneburg
state: Niedersachsen
city: Koln
country: Germany
facility: Evangelisches Krankenhaus Kalk
state: Nordrhein-westfalen
city: Leipzig
country: Germany
facility: Klinikum Sankt Georg GmbH
state: Sachsen
city: Berlin
country: Germany
facility: Krankenhaus Waldfriede
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: England
city: Harrow
country: United Kingdom
facility: London North West Healthcare NHS Trust
state: England
city: Prescot
country: United Kingdom
facility: Saint Helens and Knowsley Teaching Hospitals NHS Trust
state: England
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
state: Scotland
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: