Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

TAK-018 for Prevention of the Recurrence of Postoperative Crohn's Disease (CD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03943446
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE May 7, 2019
First Posted Date  ICMJE May 9, 2019
Last Update Posted Date January 15, 2021
Actual Study Start Date  ICMJE August 4, 2020
Estimated Primary Completion Date April 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
Percentage of Participants who Experience Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug up to Week 30 ]
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30 [ Time Frame: Weeks 3, 6, 12, 18, 26 and 30 ]
    Stool samples will be collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity.
  • Ctrough: Observed Plasma Trough Concentrations of TAK-018 [ Time Frame: Week 3 pre-dose and at multiple time points (up to 12 hours) post-dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • Percentage of Participants with Severe Endoscopic Recurrence as Assessed by Rutgeerts Scoring Scale at Weeks 12 and 26 [ Time Frame: Weeks 12 and 26 ]
    Severe endoscopic recurrence is defined as a Rutgeerts' score ≥i3 (diffuse aphthous ileitis with diffusely inflamed mucosa). The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The scale ranges from 0-4; where 0= no lesions, 1= ≤5 aphthous ulcers, 2= >5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis, 3= diffuse aphthous ileitis with diffusely inflamed mucosa and 4= diffuse inflammation with larger ulcers, nodules, and/or narrowing.
  • Percentage of Participants with Endoscopic Remission as Assessed by Rutgeerts Scoring Scale at Weeks 12 and 26 [ Time Frame: Weeks 12 and 26 ]
    Endoscopic remission is defined as a Rutgeerts' score ≤i1 (≤5 aphthous ulcers). The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The scale ranges from 0-4; where 0= no lesions, 1= ≤5 aphthous ulcers, 2= >5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis, 3= diffuse aphthous ileitis with diffusely inflamed mucosa and 4= diffuse inflammation with larger ulcers, nodules, and/or narrowing.
  • Percentage of Participants With Endoscopic Recurrence as Assessed by Rutgeerts Scoring Scale at Weeks 12 and 26 [ Time Frame: Weeks 12 and 26 ]
    Endoscopic recurrence is defined as a Rutgeerts' score ≥i2 (>5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis). The Rutgeerts scoring is a 5-point scale used to assess endoscopic recurrence at the ileocolonic anastomosis and preanastomotic ileum. The scale ranges from 0-4; where 0= no lesions, 1= ≤5 aphthous ulcers, 2= >5 aphthous ulcers with normal mucosa between lesions or lesions are confined to the anastomosis, 3= diffuse aphthous ileitis with diffusely inflamed mucosa and 4= diffuse inflammation with larger ulcers, nodules, and/or narrowing.
  • Percentage of Participants With Elevated Fecal Calprotectin at Weeks 3, 6, 12, 18 and 26 [ Time Frame: Weeks 3, 6, 12, 18 and 26 ]
    Stool samples will be collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity.
  • Ctrough: Observed Plasma Trough Concentrations of TAK-018 [ Time Frame: Week 3: Predose and at multiple timepoints (Up to 12 hours) postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TAK-018 for Prevention of the Recurrence of Postoperative Crohn's Disease (CD)
Official Title  ICMJE 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
Brief Summary The purpose of this study is to evaluate the efficacy of TAK-018 in reducing endoscopic recurrence of intestinal inflammation in postoperative participants with CD after a planned laparoscopic ileocecal resection with primary anastomosis.
Detailed Description

The drug being tested in this study is called TAK-018. 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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Crohn Disease
Intervention  ICMJE
  • Drug: TAK-018
    TAK-018 immediate-release tablets.
    Other Name: EB8018
  • Drug: TAK-018 Placebo
    TAK-018 placebo-matching tablets.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: TAK-018
  • Experimental: TAK-018 1.5 g High Dose
    TAK-018 3*0.50 g, tablets, orally, BID for up to 26 weeks.
    Intervention: Drug: TAK-018
  • Placebo Comparator: Placebo
    TAK-018 placebo-matching 3*0 g tablets, orally, BID for up to 26 weeks.
    Intervention: Drug: TAK-018 Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2020)
96
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2019)
75
Estimated Study Completion Date  ICMJE May 16, 2022
Estimated Primary Completion Date April 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-877-825-3327 medinfoUS@takeda.com
Listed Location Countries  ICMJE Austria,   France,   Germany,   United Kingdom,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT03943446
Other Study ID Numbers  ICMJE TAK-018-2001
2019-000886-19 ( EudraCT Number )
U1111-1225-5064 ( Registry Identifier: WHO )
NR266345 ( Registry Identifier: IRAS )
NL71098.018.19 ( Registry Identifier: CCMO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP