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

Takeda

Status and phase: Terminated; Phase 2

Conditions: Crohn Disease

Treatments: Drug: TAK-018; Drug: TAK-018 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03943446

TAK-018-2001

2019-000886-19 (EudraCT Number)

NR266345 (Registry Identifier)

NL71098.018.19 (Registry Identifier)

U1111-1225-5064 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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34 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: TAK-018 Placebo

TAK-018 0.30 g Low Dose

Experimental group

Description:

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

Treatment:

Drug: TAK-018

TAK-018 1.5 g High Dose

Experimental group

Description:

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

Treatment:

Drug: TAK-018