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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03943446
Recruitment Status : Terminated (Sponsor decision to discontinue study due to inability to recruit the expected number of subjects within the requisite time period.)
First Posted : May 9, 2019
Results First Posted : September 7, 2023
Last Update Posted : September 7, 2023
Sponsor:
Collaborator:
Takeda Development Center Americas, Inc.
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Crohn Disease
Interventions Drug: TAK-018
Drug: TAK-018 Placebo
Enrollment 34
Recruitment Details Participants took part in the study at 18 investigative sites in the United States, Australia, Germany, France and United Kingdom from 4 August 2020 to 25 August 2022.
Pre-assignment Details Participants with Crohn's disease (CD) who had undergone a planned laparoscopic ileocecal resection received TAK-018 for prevention of the recurrence of postoperative CD. The participants were randomized in 1:1:1 ratio to three treatment groups i.e. TAK-018 low dose, TAK-018 high dose, or placebo for a 26-week treatment period.
Arm/Group Title Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Hide Arm/Group Description TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks. TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks. TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Period Title: Overall Study
Started 12 11 11
Pharmacokinetic (PK) Analysis Set [1] 12 11 11
Completed 5 7 4
Not Completed 7 4 7
Reason Not Completed
Lost to Follow-up             0             0             1
Withdrawal by Subject             1             1             2
Study Terminated by Sponsor             1             2             1
Reason not Specified             5             1             3
[1]
PK analysis set included participants from the safety analysis set with at least 1 reported PK concentration.
Arm/Group Title Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose Total
Hide Arm/Group Description TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks. TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks. TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks. Total of all reporting groups
Overall Number of Baseline Participants 12 11 11 34
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all participants to whom study treatment had been assigned by randomization and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 11 participants 11 participants 34 participants
42.97  (13.133) 37.42  (16.179) 39.25  (11.297) 39.97  (13.457)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 11 participants 34 participants
Female
5
  41.7%
9
  81.8%
3
  27.3%
17
  50.0%
Male
7
  58.3%
2
  18.2%
8
  72.7%
17
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 11 participants 34 participants
Hispanic or Latino
1
   8.3%
1
   9.1%
0
   0.0%
2
   5.9%
Not Hispanic or Latino
9
  75.0%
7
  63.6%
10
  90.9%
26
  76.5%
Unknown or Not Reported
2
  16.7%
3
  27.3%
1
   9.1%
6
  17.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 11 participants 34 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
10
  83.3%
7
  63.6%
10
  90.9%
27
  79.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
  16.7%
4
  36.4%
1
   9.1%
7
  20.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 12 participants 11 participants 11 participants 34 participants
United States
4
  33.3%
3
  27.3%
3
  27.3%
10
  29.4%
Austria
4
  33.3%
2
  18.2%
2
  18.2%
8
  23.5%
Germany
1
   8.3%
1
   9.1%
4
  36.4%
6
  17.6%
United Kingdom
0
   0.0%
0
   0.0%
1
   9.1%
1
   2.9%
France
3
  25.0%
5
  45.5%
1
   9.1%
9
  26.5%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 12 participants 11 participants 11 participants 34 participants
171.87  (7.709) 167.95  (7.692) 172.57  (8.594) 170.83  (8.019)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 12 participants 11 participants 11 participants 34 participants
72.44  (13.514) 67.61  (15.111) 77.95  (19.971) 72.66  (16.394)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per meters squared (kg/m^2)
Number Analyzed 12 participants 11 participants 11 participants 34 participants
24.57  (4.617) 23.92  (5.037) 26.09  (6.175) 24.85  (5.214)
[1]
Measure Description: BMI was calculated based on the height and weight, using the formula: BMI (kg/m^2) = Weight (kg) / [Height (cm)* 0.01]^2.
1.Primary Outcome
Title Percentage of Participants With Endoscopic Recurrence of CD as Assessed by Rutgeerts Grading Scale at Week 26
Hide Description 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.
Time Frame At Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants to whom study treatment had been assigned by randomization and received at least 1 dose of study drug.
Arm/Group Title Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Hide Arm/Group Description:
TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.
TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks.
TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Overall Number of Participants Analyzed 12 11 11
Measure Type: Number
Unit of Measure: percentage of participants
91.7 81.8 90.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, TAK-018 0.30 g Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.590
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in ER Rate
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.44 to 0.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, TAK-018 1.5 g High Dose
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =1.000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated difference in ERR
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.34 to 0.31
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Fecal Calprotectin (FCP) >135 Microgram Per Gram (mcg/g) at Weeks 3, 6, 12, 18, 26 and 30
Hide Description Stool samples were collected for analysis of fecal calprotectin, a biomarker of intestinal inflammatory activity. Percentages are rounded off to the nearest single decimal.
Time Frame At Weeks 3, 6, 12, 18, 26 and 30
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all participants to whom study treatment had been assigned by randomization and received at least 1 dose of study drug. Overall number of participants analyzed is the number of participants available for analyses. Number analyzed indicates number of participants available for analysis at the given timepoints.
Arm/Group Title Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Hide Arm/Group Description:
TAK-018 placebo-matching tablets, orally, twice daily (BID) for up to 27.7 weeks.
TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks.
TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Overall Number of Participants Analyzed 11 8 7
Measure Type: Number
Unit of Measure: percentage of participants
At Week 3 Number Analyzed 9 participants 8 participants 7 participants
55.6 75.0 42.9
At Week 6 Number Analyzed 11 participants 8 participants 6 participants
27.3 50.0 83.3
At Week 12 Number Analyzed 9 participants 8 participants 6 participants
44.4 37.5 33.3
At Week 18 Number Analyzed 8 participants 6 participants 5 participants
75.0 50.0 60.0
At Week 26 Number Analyzed 7 participants 4 participants 4 participants
71.4 75.0 50.0
At Week 30 Number Analyzed 5 participants 6 participants 4 participants
40.0 66.7 25.0
3.Secondary Outcome
Title Ctrough: Observed Plasma Trough Concentrations of TAK-018
Hide Description [Not Specified]
Time Frame Pre-dose and at multiple time points (up to 12 hours) post-dose at Week 3
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set included participants from the safety analysis set with at least 1 reported PK concentration. Overall number of participants analyzed is the number of participants available for analyses.
Arm/Group Title TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Hide Arm/Group Description:
TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks.
TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
Overall Number of Participants Analyzed 9 5
Mean (Standard Deviation)
Unit of Measure: milligrams per Litre (mg/L)
13.8  (9.39) 36.2  (21.7)
Time Frame From the first dose of study drug up to 30 days following last dose of study drug (up to 35.98 weeks)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Hide Arm/Group Description TAK-018 placebo-matching tablets, orally, BID for up to 27.7 weeks. TAK-018 0.30 g, tablets, orally, BID for up to 31.7 weeks. TAK-018 1.5 g, tablets, orally, BID for up to 26.1 weeks.
All-Cause Mortality
Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/11 (0.00%)   0/11 (0.00%) 
Hide Serious Adverse Events
Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/12 (8.33%)   4/11 (36.36%)   2/11 (18.18%) 
Blood and lymphatic system disorders       
Blood loss anaemia † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Gastrointestinal disorders       
Mesenteric haemorrhage † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Subileus † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Varices oesophageal † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
General disorders       
Inflammation † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Hepatobiliary disorders       
Cholecystitis † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Portal vein thrombosis † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Infections and infestations       
Abdominal abscess † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications       
Abdominal wound dehiscence † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Anastomotic leak † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo TAK-018 0.30 g Low Dose TAK-018 1.5 g High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/12 (91.67%)   6/11 (54.55%)   9/11 (81.82%) 
Blood and lymphatic system disorders       
Anaemia † 1  0/12 (0.00%)  2/11 (18.18%)  0/11 (0.00%) 
Iron deficiency anaemia † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Lymphopenia † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Thrombocytopenia † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Ear and labyrinth disorders       
Ear pain † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Gastrointestinal disorders       
Abdominal discomfort † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Abdominal distension † 1  1/12 (8.33%)  1/11 (9.09%)  0/11 (0.00%) 
Abdominal pain † 1  2/12 (16.67%)  0/11 (0.00%)  1/11 (9.09%) 
Abdominal pain lower † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Abdominal pain upper † 1  1/12 (8.33%)  0/11 (0.00%)  1/11 (9.09%) 
Abdominal tenderness † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Bowel movement irregularity † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Constipation † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Crohn's disease † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Diarrhoea † 1  2/12 (16.67%)  2/11 (18.18%)  0/11 (0.00%) 
Dyspepsia † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Gastritis † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Gastrooesophageal reflux disease † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Nausea † 1  3/12 (25.00%)  1/11 (9.09%)  3/11 (27.27%) 
Vomiting † 1  5/12 (41.67%)  0/11 (0.00%)  2/11 (18.18%) 
General disorders       
Fatigue † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Peripheral swelling † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Infections and infestations       
COVID-19 † 1  1/12 (8.33%)  1/11 (9.09%)  1/11 (9.09%) 
Escherichia urinary tract infection † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Influenza † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Respiratory tract infection † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Sepsis † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Tinea versicolour † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Urinary tract infection † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications       
Post procedural discomfort † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Procedural pain † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Investigations       
Blood phosphorus decreased † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
C-reactive protein increased † 1  3/12 (25.00%)  2/11 (18.18%)  1/11 (9.09%) 
Faecal calprotectin increased † 1  3/12 (25.00%)  0/11 (0.00%)  0/11 (0.00%) 
Haematocrit decreased † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Haemoglobin decreased † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Hepatic enzyme increased † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Platelet count increased † 1  1/12 (8.33%)  1/11 (9.09%)  0/11 (0.00%) 
Red blood cell count decreased † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Back pain † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Muscle tightness † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Muscle twitching † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Nervous system disorders       
Dysgeusia † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Neuralgia † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Tremor † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Psychiatric disorders       
Anxiety † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Depression † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Insomnia † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Reproductive system and breast disorders       
Endometriosis † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia † 1  0/12 (0.00%)  1/11 (9.09%)  1/11 (9.09%) 
Dermatitis contact † 1  0/12 (0.00%)  1/11 (9.09%)  0/11 (0.00%) 
Pruritus † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Rash † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Sensitive skin † 1  0/12 (0.00%)  0/11 (0.00%)  1/11 (9.09%) 
Vascular disorders       
Flushing † 1  1/12 (8.33%)  0/11 (0.00%)  0/11 (0.00%) 
Hypertension † 1  2/12 (16.67%)  0/11 (0.00%)  0/11 (0.00%) 
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
This study is terminated as the sponsor decided to discontinue study due to inability to recruit the expected number of participants within the requisite time period.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03943446    
Other Study ID Numbers: TAK-018-2001
2019-000886-19 ( EudraCT Number )
U1111-1225-5064 ( Registry Identifier: WHO )
NR266345 ( Registry Identifier: IRAS )
NL71098.018.19 ( Registry Identifier: CCMO )
First Submitted: May 7, 2019
First Posted: May 9, 2019
Results First Submitted: August 11, 2023
Results First Posted: September 7, 2023
Last Update Posted: September 7, 2023