Clinical Trial Results:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-062 for the Treatment of Active Celiac Disease in Subjects Attempting a Gluten-Free Diet
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Summary
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EudraCT number |
2020-005438-14 |
Trial protocol |
FR ES Outside EU/EEA BE PL IT |
Global end of trial date |
06 Nov 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Aug 2025
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First version publication date |
17 Aug 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TAK-062-2001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05353985 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Ave, Lexington, MA, United States, 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-003116-PIP01-21 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Nov 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Nov 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main aim of this trial was to assess the efficacy and safety of TAK-062 for the treatment of symptoms and intestinal damage related to inadvertent gluten exposure in participants with celiac disease.
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Protection of trial subjects |
Each participant or their legally authorized representative signed an informed consent form (ICF) before participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jun 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 6
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Poland: 17
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Country: Number of subjects enrolled |
Italy: 11
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
United States: 105
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Worldwide total number of subjects |
153
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EEA total number of subjects |
38
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
143
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at various investigative sites globally from 30 June 2022 to 06 November 2024. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants with diagnosis of celiac disease were enrolled & randomly assigned to receive either TAK-062 Placebo + SIGE Gluten-Bar or pre-determined amount of TAK-062 + SIGE Gluten-Bar in Cohort 1. 153 participants were enrolled in the trial but 1 participant out of 153 was randomized but not treated. Cohort 2 of trial was not initiated. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo + SIGE Gluten-Bar | ||||||||||||||||||||||||||||||
Arm description |
Participants received TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
TAK-062
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Investigational medicinal product code |
TAK-062
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks.
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Arm title
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TAK-062 + SIGE Gluten-Bar | ||||||||||||||||||||||||||||||
Arm description |
Participants received pre-determined amount of TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
TAK-062
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Investigational medicinal product code |
TAK-062
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo + SIGE Gluten-Bar
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Reporting group description |
Participants received TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-062 + SIGE Gluten-Bar
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Reporting group description |
Participants received pre-determined amount of TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo + SIGE Gluten-Bar
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Reporting group description |
Participants received TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks. | ||
Reporting group title |
TAK-062 + SIGE Gluten-Bar
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Reporting group description |
Participants received pre-determined amount of TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks. | ||
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End point title |
Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score from Baseline to Week 12 | ||||||||||||
End point description |
CDSD GI symptom severity score is an average of the daily GI symptom severity scores during the week. The daily GI symptom severity score is the average of the severity score for diarrhea, abdominal pain, bloating and nausea, ranging from 0 to 4. Symptom severity is evaluated using 5-point Likert-type scales (none, mild, moderate, severe, and very severe). Higher scores indicate more severe symptoms. Results are reported as least squares (LS) mean change from baseline at Week 12, determined using a mixed-effect model for repeated measures (MMRM). A negative change from baseline indicates improvement. The FAS–SIGE included all randomized participants who were randomized to receive gluten-containing SIGE. Subjects analysed is the number of participants with data available for analysis. Cohort 2 of the trial was not initiated.
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End point type |
Primary
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End point timeframe |
Baseline (Week -1) to Week 12
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Statistical analysis title |
Change in Weekly CDSD GI Symptom Severity Score | ||||||||||||
Comparison groups |
Placebo + SIGE Gluten-Bar v TAK-062 + SIGE Gluten-Bar
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Number of subjects included in analysis |
120
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.847 [1] | ||||||||||||
Method |
MMRM | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
0.017
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.162 | ||||||||||||
upper limit |
0.197 | ||||||||||||
| Notes [1] - P-value was based on MMRM analysis with treatment group, week, treatment-by-week interaction, & the randomization stratification factors as fixed effects & baseline CDSD GI symptom severity scores as covariates, and participant as a random effect. |
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End point title |
Change in Villous Height to Crypt Depth Ratio (Vh:Cd) from Baseline to Week 24 | ||||||||||||
End point description |
The Vh:Cd ratio represents mucosal architectural changes and a lower Vh:Cd ratio indicates more severe intestinal injury characterized by a flattening of the mucosa. Results are reported as least squares (LS) mean change from baseline at Week 24, determined using an analysis of covariance (ANCOVA) model. A negative change from baseline indicates worsening disease. The FAS–SIGE included all randomized participants who were randomized to receive gluten-containing SIGE. Subjects analyzed is the number of participants with data available for analysis. Cohort 2 of the trial was not initiated.
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End point type |
Secondary
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End point timeframe |
Baseline (Week -4, Run-in Period) to Week 24
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Statistical analysis title |
Change in Vh:Cd from Baseline to Week 24 | ||||||||||||
Comparison groups |
Placebo + SIGE Gluten-Bar v TAK-062 + SIGE Gluten-Bar
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Number of subjects included in analysis |
119
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [2] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||
Point estimate |
-0.331
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.481 | ||||||||||||
upper limit |
-0.181 | ||||||||||||
| Notes [2] - P-value was based on a ANCOVA model with treatment group and randomization stratification factors as fixed effects and baseline Vh:Cd as covariates. |
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End point title |
Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | |||||||||||||||||||||
End point description |
Adverse event=any untoward medical occurrence in clinical investigation participant administered a drug;it does not necessarily have to have causal relationship with this treatment.AE can therefore be any unfavorable&unintended sign(e.g.,clinically significant abnormal laboratory value,electrocardiogram[ECG] value,or vital sign measurement),symptom,or disease temporally associated with use of drug whether or not it is considered related to drug.TEAE=new onset or worsening AEs after first dose of study treatment regardless of relationship to study drug.SAE=any untoward medical occurrence at any dose that results in death,is life threatening,requires inpatient hospitalization/prolongation of existing hospitalization,results in persistent/significant disability/incapacity,leads to a congenital anomaly/birth defect/is important medical event.TEAEs considered related to study drug as assessed by investigator were reported.Percentages were rounded off to nearest single decimal place. SAF.
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End point type |
Secondary
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End point timeframe |
Up to Week 28
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Participants with Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | ||||||||||||||||||
End point description |
A positive ADA participant was defined as a participant who had at least 1 positive ADA result during the study and was further categorized as: Transiently positive- defined as participants with confirmed positive ADA in at least 1 sample and no consecutive samples; Persistently positive- defined as participants with confirmed positive ADA in 2 or more consecutive positive ADA samples. Immunogenicity Analysis Set included all randomized participants who received any TAK-062 and had the baseline and at least 1 postbaseline immunogenicity sample assessment.
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End point type |
Secondary
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End point timeframe |
Up to Week 28
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to Week 28
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Adverse event reporting additional description |
The SAF included all randomized participants who received at least 1 dose of study drug.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
TAK-062 Placebo + SIGE Gluten-Bar
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Reporting group description |
Participants received TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
TAK-062 + SIGE Gluten-Bar
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Reporting group description |
Participants received pre-determined amount of TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Jun 2022 |
The following changes were made as per amendment 1.0: 1. Addition of an exclusion criterion to exclude participants with known hypersensitivity reaction and/or allergy, including anaphylaxis, to wheat and/or gluten. |
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22 Jul 2022 |
The following changes were made as per amendment 2.0: 1. Addition of an exclusion criterion to exclude participants with known history of hypersensitivity, idiosyncratic reaction, or intolerance to any ingredients or excipients in TAK-062 and/or placebo. 2. Addition of the number of TAK-062 and placebo tablets administered for each cohort. |
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26 Oct 2022 |
The following changes were made as per amendment 3.0: 1. Revised the number of study sites. 2. Villous height to crypt depth ratio (Vh:Cd) revised. 3. Removed the internal review committee. 4. Increased the number of participants in the TAK-062 placebo plus SIGE bar treatment group from 30 to 50. 5. Added the TAK-062 treatment group for adolescents and revised the number of participants based on this addition. 5. Revised exclusion criterion to add a maximum of 20% of adult participants without a producible initial biopsy report to be included if they have serology or histology confirmation at screening. 6. Added aspartate aminotransferase (AST) ≥3 × upper limit of normal (ULN) as an exclusion criterion. 6. Added region-specific exclusion criteria for participants enrolling in France. |
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02 Jun 2023 |
The following changes were made as per amendment 4.0: 1. Updated the number of sites. 2. Corrected error in the study design diagram. 3. The broad term ‘mucosal injury’ was replaced with a specific description ‘villous atrophy’. 4. Changed simulated inadvertent gluten exposure (SIGE) run-in period to Week -2 through Day -1 instead of Week 2 through Day -1. 5. Revised inclusion and exclusion criteria. |
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16 Nov 2023 |
The following changes were made as per amendment 5.0: 1. Updated the planned approximate sample size from 377 to 357 to account for the combining of participants within the placebo gluten-containing SIGE arms from Cohorts 1 and 2 for analysis. 2. Updated the approximate number of participants to be enrolled in Cohort 2 from 257 to 237. 3. Updated the approximate number of participants to be enrolled to Cohort 2 Group 1 (TAK-062 placebo 3 times a day [TID] + SIGE bar 3 times a week [TIW] from 50 to 30. 3. Added the number of adults and adolescent participants per cohort. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
