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Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma

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ClinicalTrials.gov Identifier: NCT02723006
Recruitment Status : Terminated (Business decision: Protocol efficacy futility met)
First Posted : March 30, 2016
Results First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Melanoma
Interventions Drug: TAK-580
Drug: TAK-202
Drug: vedolizumab
Drug: nivolumab
Drug: ipilimumab
Enrollment 22
Recruitment Details Participants took part in the study at 10 investigative sites in the United States from 22 June 2016 to 11 May 2018.
Pre-assignment Details Participants with advanced/metastatic melanoma were enrolled to receive:TAK-580+nivolumab,TAK-202+nivolumab,or vedolizumab+nivolumab+ipilumab. Study was terminated early after the dose escalation safety-lead in phase due to lack of enrollment(Arm 1), lack of clinical benefit(Arm 2), and after pre-specified stopping rule for diarrhea was met(Arm 3).
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description Participants in this group received TAK-580 400 milligram (mg), tablets, orally, once weekly along with nivolumab 3 milligram per kilogram (mg/kg), infusion, intravenous, once every 2 weeks (up to Week 48). Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Period Title: Overall Study
Started 1 9 12
Completed 0 2 5
Not Completed 1 7 7
Reason Not Completed
Withdrawal by Subject             0             1             1
Study Terminated by Sponsor             1             6             6
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab Total
Hide Arm/Group Description Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48). Total of all reporting groups
Overall Number of Baseline Participants 1 9 12 22
Hide Baseline Analysis Population Description
The safety analysis set included all participants who received at least 1 dose, even if incomplete, of study treatment (TAK-580, TAK-202, or vedolizumab).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1 participants 9 participants 12 participants 22 participants
41 63.9  (11.54) 55.8  (16.36) 58.5  (14.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 9 participants 12 participants 22 participants
Female
1
 100.0%
3
  33.3%
7
  58.3%
11
  50.0%
Male
0
   0.0%
6
  66.7%
5
  41.7%
11
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 9 participants 12 participants 22 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
1
 100.0%
9
 100.0%
9
  75.0%
19
  86.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
3
  25.0%
3
  13.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 9 participants 12 participants 22 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%
1
  11.1%
0
   0.0%
1
   4.5%
White
1
 100.0%
8
  88.9%
11
  91.7%
20
  90.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   8.3%
1
   4.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 1 participants 9 participants 12 participants 22 participants
1
 100.0%
9
 100.0%
12
 100.0%
22
 100.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 1 participants 9 participants 12 participants 22 participants
171.00 168.49  (10.479) 170.00  (10.846) 169.40  (10.170)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 1 participants 9 participants 12 participants 22 participants
77.80 77.42  (9.248) 88.20  (26.786) 83.32  (20.937)
1.Primary Outcome
Title Number of Dose Limiting Toxicities (DLTs) During the Dose-escalation Safety Lead-in Phase
Hide Description DLTs was evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time Frame TAK-580 + Nivolumab and TAK-202 + Nivolumab: Baseline up to Week 9; Vedolizumab + Nivolumab + Ipilimumab: Baseline up to Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose, even if incomplete, of study treatment (TAK-580, TAK-202, or vedolizumab).
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 1 9 12
Measure Type: Number
Unit of Measure: DLTs
0 3 0
2.Secondary Outcome
Title Overall Response Rate (ORR) During the Dose-escalation Safety Lead-in Phase
Hide Description ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. was the percentage of participants with complete response (CR) or partial response (PR). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.
Time Frame Baseline up to Week 50
Hide Outcome Measure Data
Hide Analysis Population Description
Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea.
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Duration of Response (DOR) During the Dose-escalation Safety Lead-in Phase
Hide Description DOR based on RECIST version 1.1 was the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever occurred first. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. PR: at least 30% decrease in SOD of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame From date of first documented confirmed CR/PR until date of first documentation of PD or death (up to Week 50)
Hide Outcome Measure Data
Hide Analysis Population Description
Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea.
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Progression-free Survival (PFS) During the Dose-escalation Safety Lead-in Phase
Hide Description PFS was the time from first dose date to date of the first documentation of confirmed PD or death, whichever occurred first. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions.
Time Frame From first dose date to the date of the first documentation of confirmed PD or death (up to Week 50)
Hide Outcome Measure Data
Hide Analysis Population Description
Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea.
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Overall Survival (OS) During the Dose-escalation Safety Lead-in Phase
Hide Description OS was the time from date of first dose of study drug until date of death from any cause.
Time Frame From first dose of study drug until date of death from any cause (up to Week 50)
Hide Outcome Measure Data
Hide Analysis Population Description
Planned efficacy analyses was not performed as the study was terminated due to lack of enrollment, lack of clinical benefit and after the pre-specified stopping rule was met for diarrhea.
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame From the first dose of study drug up to 30 days after the last dose of study drug (up to Week 50)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all participants who received at least 1 dose, even if incomplete, of study treatment (TAK-580, TAK-202, or vedolizumab).
Arm/Group Title Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description:
Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48).
Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50).
Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
Overall Number of Participants Analyzed 1 9 12
Measure Type: Number
Unit of Measure: participants
TEAEs 1 9 12
SAEs 1 2 7
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (up to Week 50) after the last dose of study drug
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 Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Hide Arm/Group Description Participants in this group received TAK-580 400 mg, tablets, orally, once weekly along with nivolumab 3 mg/kg, infusion, intravenous, once every 2 weeks (up to Week 48). Participants in this group received TAK-202 (plozalizumab) 4 mg/kg titrated up to 8 mg/kg (stable dose), infusion, intravenous, once in Weeks 1, 3, 5, and every 4 weeks thereafter along with nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks (up to Week 50). Participants in this group received vedolizumab 200 mg titrated up to 450 mg (stable dose), infusion, intravenously, once in Weeks 1, 3, 5, and 13 along with ipilimumab 3 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses and nivolumab 1 mg/kg, infusion, intravenously, once every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg, infusion, intravenously, once every 2 weeks until disease progression or unacceptable toxicity (up to Week 48).
All-Cause Mortality
Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/1 (0.00%)      0/9 (0.00%)      2/12 (16.67%)    
Hide Serious Adverse Events
Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      2/9 (22.22%)      7/12 (58.33%)    
Blood and lymphatic system disorders       
Eosinophilia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Leukocytosis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Cardiac disorders       
Acute coronary syndrome  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Endocrine disorders       
Adrenal insufficiency  1  1/1 (100.00%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Hypophysitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders       
Nausea  1  1/1 (100.00%)  1 1/9 (11.11%)  1 0/12 (0.00%)  0
Autoimmune colitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Colitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Diarrhoea  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Rectal haemorrhage  1  0/1 (0.00%)  0 1/9 (11.11%)  2 0/12 (0.00%)  0
General disorders       
Pyrexia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations       
Appendicitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Injury, poisoning and procedural complications       
Spinal compression fracture  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Investigations       
International normalised ratio increased  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastatic malignant melanoma  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm 1: TAK-580 + Nivolumab Arm 2: TAK-202 + Nivolumab Arm 3: Vedolizumab + Ipilimumab + Nivolumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      9/9 (100.00%)      12/12 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  0/1 (0.00%)  0 1/9 (11.11%)  1 4/12 (33.33%)  7
Eosinophilia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Leukocytosis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Thrombocytopenia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Cardiac disorders       
Atrial fibrillation  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Palpitations  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Sinus tachycardia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  3
Ear and labyrinth disorders       
Tinnitus  1  0/1 (0.00%)  0 0/9 (0.00%)  0 2/12 (16.67%)  2
Ear discomfort  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Endocrine disorders       
Hypothyroidism  1  0/1 (0.00%)  0 4/9 (44.44%)  5 3/12 (25.00%)  3
Adrenal insufficiency  1  0/1 (0.00%)  0 0/9 (0.00%)  0 4/12 (33.33%)  4
Hyperthyroidism  1  0/1 (0.00%)  0 0/9 (0.00%)  0 3/12 (25.00%)  3
Eye disorders       
Conjunctivitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Conjunctivitis allergic  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Dry eye  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Vision blurred  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Visual impairment  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders       
Nausea  1  1/1 (100.00%)  3 6/9 (66.67%)  7 8/12 (66.67%)  10
Diarrhoea  1  0/1 (0.00%)  0 3/9 (33.33%)  5 5/12 (41.67%)  12
Abdominal pain  1  0/1 (0.00%)  0 3/9 (33.33%)  4 4/12 (33.33%)  8
Constipation  1  0/1 (0.00%)  0 2/9 (22.22%)  3 3/12 (25.00%)  4
Dry mouth  1  1/1 (100.00%)  1 1/9 (11.11%)  2 2/12 (16.67%)  2
Vomiting  1  1/1 (100.00%)  6 2/9 (22.22%)  3 1/12 (8.33%)  2
Oropharyngeal pain  1  0/1 (0.00%)  0 2/9 (22.22%)  2 1/12 (8.33%)  1
Oral pain  1  1/1 (100.00%)  1 1/9 (11.11%)  1 0/12 (0.00%)  0
Abdominal discomfort  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Abdominal distension  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Anorectal disorder  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Autoimmune colitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Duodenitis  1  1/1 (100.00%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Dyspepsia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Dysphagia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Eosinophilic oesophagitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Gastrooesophageal reflux disease  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Gingival bleeding  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Rectal haemorrhage  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Stomatitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
General disorders       
Fatigue  1  1/1 (100.00%)  2 4/9 (44.44%)  8 9/12 (75.00%)  12
Pyrexia  1  1/1 (100.00%)  1 3/9 (33.33%)  5 5/12 (41.67%)  9
Chills  1  0/1 (0.00%)  0 4/9 (44.44%)  5 0/12 (0.00%)  0
Influenza like illness  1  0/1 (0.00%)  0 1/9 (11.11%)  1 2/12 (16.67%)  2
Oedema peripheral  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Facial pain  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Gait disturbance  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Infusion site reaction  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Localised oedema  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Thirst  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Hepatobiliary disorders       
Autoimmune hepatitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Immune-mediated hepatitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Immune system disorders       
Drug hypersensitivity  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Seasonal allergy  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations       
Candida infection  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Skin infection  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Urinary tract infection  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Acarodermatitis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Bacterascites  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Bacterial infection  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Cellulitis  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Influenza  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Injury, poisoning and procedural complications       
Incision site haemorrhage  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  0/1 (0.00%)  0 2/9 (22.22%)  4 2/12 (16.67%)  4
Aspartate aminotransferase increased  1  0/1 (0.00%)  0 2/9 (22.22%)  3 1/12 (8.33%)  1
Amylase increased  1  1/1 (100.00%)  1 0/9 (0.00%)  0 1/12 (8.33%)  1
Weight decreased  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Blood alkaline phosphatase increased  1  0/1 (0.00%)  0 1/9 (11.11%)  2 0/12 (0.00%)  0
Eosinophil percentage increased  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Heart rate increased  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Lipase increased  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Neutrophil count decreased  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Platelet count decreased  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Thyroid function test abnormal  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
White blood cell count decreased  1  0/1 (0.00%)  0 1/9 (11.11%)  2 0/12 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  0/1 (0.00%)  0 3/9 (33.33%)  4 2/12 (16.67%)  2
Dehydration  1  1/1 (100.00%)  1 0/9 (0.00%)  0 3/12 (25.00%)  3
Hypokalaemia  1  1/1 (100.00%)  1 0/9 (0.00%)  0 1/12 (8.33%)  1
Hyponatraemia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 2/12 (16.67%)  2
Hyperglycaemia  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Hyperkalaemia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Hyperuricaemia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Hypoalbuminaemia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Hypocalcaemia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Hypoglycaemia  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/1 (100.00%)  1 2/9 (22.22%)  4 2/12 (16.67%)  2
Back pain  1  0/1 (0.00%)  0 0/9 (0.00%)  0 3/12 (25.00%)  3
Muscular weakness  1  0/1 (0.00%)  0 0/9 (0.00%)  0 2/12 (16.67%)  2
Musculoskeletal chest pain  1  0/1 (0.00%)  0 0/9 (0.00%)  0 2/12 (16.67%)  2
Myalgia  1  0/1 (0.00%)  0 2/9 (22.22%)  2 0/12 (0.00%)  0
Neck pain  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Arthritis  1  0/1 (0.00%)  0 1/9 (11.11%)  3 0/12 (0.00%)  0
Joint swelling  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Muscle spasms  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal pain  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Pain in extremity  1  1/1 (100.00%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders       
Headache  1  1/1 (100.00%)  1 3/9 (33.33%)  4 5/12 (41.67%)  10
Dizziness  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Ataxia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Dysgeusia  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Neuropathy peripheral  1  1/1 (100.00%)  1 0/9 (0.00%)  0 0/12 (0.00%)  0
Paraesthesia  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Peripheral motor neuropathy  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Tremor  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Psychiatric disorders       
Insomnia  1  0/1 (0.00%)  0 1/9 (11.11%)  2 1/12 (8.33%)  1
Anxiety  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Depression  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Hallucination, visual  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Mental status changes  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Renal and urinary disorders       
Acute kidney injury  1  1/1 (100.00%)  1 0/9 (0.00%)  0 1/12 (8.33%)  1
Dysuria  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Micturition frequency decreased  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Nephrolithiasis  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Pollakiuria  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/1 (0.00%)  0 3/9 (33.33%)  3 4/12 (33.33%)  4
Dyspnoea  1  0/1 (0.00%)  0 1/9 (11.11%)  1 2/12 (16.67%)  3
Nasal congestion  1  0/1 (0.00%)  0 0/9 (0.00%)  0 3/12 (25.00%)  3
Epistaxis  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Productive cough  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Rhinorrhoea  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Sinus congestion  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders       
Pruritus  1  0/1 (0.00%)  0 1/9 (11.11%)  1 6/12 (50.00%)  10
Rash  1  0/1 (0.00%)  0 1/9 (11.11%)  4 4/12 (33.33%)  4
Rash maculo-papular  1  0/1 (0.00%)  0 2/9 (22.22%)  2 3/12 (25.00%)  3
Dermatitis acneiform  1  1/1 (100.00%)  3 1/9 (11.11%)  1 0/12 (0.00%)  0
Hyperhidrosis  1  0/1 (0.00%)  0 2/9 (22.22%)  4 0/12 (0.00%)  0
Night sweats  1  0/1 (0.00%)  0 1/9 (11.11%)  1 1/12 (8.33%)  1
Dry skin  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  2
Hypohidrosis  1  0/1 (0.00%)  0 1/9 (11.11%)  1 0/12 (0.00%)  0
Pruritus generalised  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Rash erythematous  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Rash papular  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Rash pruritic  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
Vascular disorders       
Hypotension  1  0/1 (0.00%)  0 0/9 (0.00%)  0 1/12 (8.33%)  1
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
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.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
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 ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02723006    
Other Study ID Numbers: C28003
U1111-1177-4142 ( Other Identifier: WHO )
2015-005554-35 ( EudraCT Number )
First Submitted: March 25, 2016
First Posted: March 30, 2016
Results First Submitted: May 1, 2019
Results First Posted: April 1, 2021
Last Update Posted: April 1, 2021