Crohn DiseasePhase 2NCT03943446
A Study of TAK-018 in Preventing the Recurrence of Crohn's Disease After Surgery
A Phase 2 study testing TAK-018 in people with Crohn Disease, run by Takeda at 41 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- TAK-018
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 41 sitesin 5 countries
- Study dates
- 4 Aug 2020to 25 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
41 sites in 5 countries.
41 sites in 5 countries
United States23 sites
Atlanta Gastroenterology Associates
Atlanta, Georgia, 30342
University of Colorado Hospital Anschutz Cancer Pavilion
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21205
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of North Carolina School of Medicine
Chapel Hill, North Carolina, 27599-7032
Atrium Health
Charlotte, North Carolina, 28204
Northwestern University
Chicago, Illinois, 60611
The University of Chicago Medical Center
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
Houston Methodist Hospital
Houston, Texas, 77030-2740
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Kentucky Chandler Medical Center
Lexington, Kentucky, 40536
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Hoag Memorial Hospital Presbyterian
Los Angeles, California, 92618
University of Miami Leonard M. Miller School of Medicine
Miami, Florida, 33136
Vanderbilt Inflammatory Bowel Disease Clinic
Nashville, Tennessee, 37212-1375
NYU Langone Inflammatory Bowel Disease Center
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Columbia University Irving Medical Center
New York, New York, 10032
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213-2536
University of South Florida/USF Health
Tampa, Florida, 33612
France6 sites
Centre Hospitalier Universitaire Estaing
Clermont-Ferrand, Auvergne, 63003
Centre Hospitalier Universitaire de Nice Hopital l'Archet
Nice, Provence-Alpes-Côte d'Azur Region, 06202
Hopital Saint-Louis
Paris, Il-de-France, 75475
Hopital Pontchaillou
Rennes, Brittany Region, 35033
Les Hopitaux Universitaires de Strasbourg - Hopital Hautepierre
Strasbourg, Alsace, 67200
Hopital Rangueil
Toulouse, Midi-pyrenees, 31059
Germany6 sites
Krankenhaus Waldfriede
Berlin, 14163
Evangelisches Krankenhaus Kalk
Cologne, North Rhine-Westphalia, 51103
Universitatsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Klinikum Sankt Georg GmbH
Leipzig, Saxony, 04129
Klinikum Luneburg
Lüneburg, Lower Saxony, 21339
Universitatsmedizin Mannheim
Mannheim, Baden-Wurttemberg, 68167
United Kingdom4 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, England, B15 2TH
NHS Greater Glasgow and Clyde
Glasgow, Scotland, G51 4TF
London North West Healthcare NHS Trust
Harrow, England, HA1 3UJ
Saint Helens and Knowsley Teaching Hospitals NHS Trust
Prescot, England, L35 5DR
Austria2 sites
Medizinische Universitat Innsbruck
Innsbruck, Tyrol, 6020
Allgemeines Krankenhaus Wien
Vienna, State of Vienna, 1090
About this study
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
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.
Read the 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.
- Conditions
- Crohn Disease
- Being tested
- TAK-018, TAK-018 Placebo
- Keywords
- Drug Therapy
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAK-018Drug
Also called Sibofimloc
TAK-018 immediate-release tablets.
TAK-018 PlaceboDrug
TAK-018 placebo-matching tablets.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks. Receives: 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. Receives: 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. Receives: Drug: TAK-018 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Stool samples were collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity. Percentages are rounded off to the nearest single decimal.
Measured: At Weeks 3, 6, 12, 18, 26 and 30
Ctrough: Observed Plasma Trough Concentrations of TAK-018
Measured: Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start4 Aug 2020
- Primary completion25 Aug 2022
- Study completion25 Aug 2022
Why it stopped: Sponsor decision to discontinue study due to inability to recruit the expected number of subjects within the requisite time period.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03943446
- Sponsor's protocol ID
- TAK-018-2001
- Other IDs
- 2019-000886-19, U1111-1225-5064, NR266345, NL71098.018.19, 2019
- Status last verified
- Aug 2023
- First submitted
- 7 May 2019
- Last updated
- 7 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03943446
- Acronym / sponsor ID
- TAK-018-2001
- Conditions
- Crohn Disease
- Keywords
- Drug Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision to discontinue study due to inability to recruit the expected number of subjects within the requisite time period.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Collaborators
- Takeda Development Center Americas, Inc.
- Study start
- 4 Aug 2020 (actual)
- Primary completion
- 25 Aug 2022 (actual)
- Study completion
- 25 Aug 2022 (actual)
- First posted
- 9 May 2019 (actual)
- Results
- Posted 7 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: TAK-018 PlaceboTAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks. |
| TAK-018 0.30 g Low Dose | Experimental | Drug: TAK-018TAK-018 0.30 gram (g), tablets, orally, BID for up to 31.7 weeks. |
| TAK-018 1.5 g High Dose | Experimental | Drug: TAK-018TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAK-018Also: SibofimlocTAK-018 immediate-release tablets. | Drug | TAK-018 0.30 g Low Dose, TAK-018 1.5 g High Dose |
| TAK-018 PlaceboTAK-018 placebo-matching tablets. | Drug | Placebo |
Primary outcome
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26
Time frame: 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.
2 secondary outcomes
Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30
Time frame: At Weeks 3, 6, 12, 18, 26 and 30
Ctrough: Observed Plasma Trough Concentrations of TAK-018
Time frame: Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain more information about this study, click this link.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
41 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TAK-018 in people with Crohn Disease, run by Takeda at 41 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, France, Germany, United Kingdom, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26 (time frame: At Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2023.