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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: TAK-018
* Drug: TAK-018 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks. | Drug: TAK-018 Placebo<br>* TAK-018 placebo-matching tablets.<br>|
| Experimental: TAK-018 0.30 g Low Dose<br>TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks. | Drug: TAK-018<br>* TAK-018 immediate-release tablets.<br>* Other names: Sibofimloc;|
| Experimental: TAK-018 1.5 g High Dose<br>TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks. | Drug: TAK-018<br>* TAK-018 immediate-release tablets.<br>* Other names: Sibofimloc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Ctrough: Observed Plasma Trough Concentrations of TAK-018 |  | Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy