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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04530123




Registration number
NCT04530123
Ethics application status
Date submitted
25/08/2020
Date registered
28/08/2020
Date last updated
1/07/2025

Titles & IDs
Public title
Dose-Ranging Study of the Efficacy and Safety of TAK-101 for Prevention of Gluten-Specific T Cell Activation in Participants With Celiac Disease on a Gluten-Free Diet
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-101 for the Prevention of Gluten-Specific T Cell Activation in Subjects With Celiac Disease on a Gluten-Free Diet
Secondary ID [1] 0 0
U1111-1253-8169
Secondary ID [2] 0 0
TAK-101-2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac Disease 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - TAK-101
Treatment: Other - Gluten

Experimental: Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE - Following a single-day 3 gram (g) oral run-in gluten challenge, participants will receive TAK-101 placebo-matching intravenous (IV) infusion dose, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 25 microgram per kilogram (µg/kg) GE will be given 23 weeks after the second dose at approximately Week 24.

Experimental: Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 25 µg/kg, IV infusion once on Day 1 followed by TAK-101 placebo-matching IV infusion, once on Day 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24.

Experimental: Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 25 µg/kg GE IV infusion, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24.

Experimental: Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 placebo-matching IV infusion, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.

Experimental: Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 50 µg/kg GE IV infusion, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 50 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.

Experimental: Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 placebo-matching IV infusion, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 12.5 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1. This group would be opened only if it is decided not to open Cohort 2 at the 50 µg/kg GE dose level.

Experimental: Cohort 2, Group F: TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GE - Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 12.5 µg/kg GE IV infusion, once each on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. A third IV infusion dose of TAK-101 12.5 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.


Treatment: Drugs: Placebo
TAK-101 placebo-matching intravenous infusion

Treatment: Drugs: TAK-101
TAK 101 intravenous infusion

Treatment: Other: Gluten
Powder form (vital wheat gluten)

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Interferon-gamma Spot Forming Units (IFN-? SFUs) in Human Leukocyte Antigens Density Quotient (HLA-DQ2.5-positive) Participants Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay
Assessment method [1] 0 0
IFN-? SFUs will be measured based on results of a gliadin-specific ELISpot assay using gluten-specific T cells which will be isolated from blood.
Timepoint [1] 0 0
Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20)
Secondary outcome [1] 0 0
Percentage of Participants Experiencing at Least One Adverse Event (AE) and Adverse Events of Special Interest (AESIs)
Assessment method [1] 0 0
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 (e.g., a markedly abnormal physical examination finding, vital sign value, laboratory test value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. An AESI (serious or nonserious) is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.
Timepoint [1] 0 0
From the first IV dose up to 30 days after last IV dose (Up to Week 28)
Secondary outcome [2] 0 0
Change From Run-in (Visit 2) to Weeks 8, 14, and 20 in the Pre- to Post-gluten Challenge Change of the 3-day Average Nausea Severity Score as Measured in Celiac Disease Symptom Diary (CDSD)
Assessment method [2] 0 0
The CDSD version 2.1 is an 8-item, self-administered questionnaire that evaluates the celiac disease (CeD) symptoms using 5-point Likert-type scales, where lower score indicating no symptoms and higher score indicating severe symptoms for all items except for frequency questions relating to stool counts, diarrhea, and vomiting frequency. The scores from the past 3 days with a 24-hour recall period will be averaged. For Weeks 8, 14, and 20, it is calculated as the average of the available daily scores recorded in the 3 days prior and after the respective gluten challenge.
Timepoint [2] 0 0
Run-in (Visit 2), Weeks 8, 14, and 20
Secondary outcome [3] 0 0
Change From Run-in (Visit 2) to Weeks 8,14, and 20 in the Pre- to Post-gluten Challenge Change in CDSD 3-day Peak Nausea Severity Score
Assessment method [3] 0 0
The CDSD version 2.1 is an 8-item, self-administered questionnaire that evaluates the CeD symptoms using 5-point Likert-type scales, where lower score indicating no symptoms and higher score indicating severe symptoms for all items except for frequency questions relating to stool counts, diarrhea, and vomiting frequency. The scores from the past 3 days with a 24-hour recall period will be averaged. Peak score is the highest score in the 3 days prior and following gluten challenge at Weeks 8, 14, and 20.
Timepoint [3] 0 0
Run-in (Visit 2), Weeks 8, 14, and 20
Secondary outcome [4] 0 0
Change From Run-in (Visit 2) to Weeks 8, 14, and 20 in the Pre- to Post-gluten Challenge Change in Weekly Gastrointestinal (GI) Symptom Severity Score
Assessment method [4] 0 0
The CDSD version 2.1 is an 8-item, self-administered questionnaire that evaluates the CeD symptoms using 5-point Likert-type scales, where lower score indicating no symptoms and higher score indicating severe symptoms for all items except for frequency questions relating to stool counts, diarrhea, and vomiting frequency. GI symptom severity score ranges from 0 to 20 with higher score indicating more severe disease.
Timepoint [4] 0 0
Run-in (Visit 2), Weeks 8, 14, and 20
Secondary outcome [5] 0 0
Fold Change in Plasma Interleukin-2 (IL-2) from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20
Assessment method [5] 0 0
The pre-/post-gluten challenge fold change in plasma IL-2 from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20 will be compared.
Timepoint [5] 0 0
Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20
Secondary outcome [6] 0 0
Fold Change in Plasma IL-2 at Specified Time Points
Assessment method [6] 0 0
The pre-/post-gluten challenge fold change in plasma IL-2 at each of the time points will be compared.
Timepoint [6] 0 0
Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20
Secondary outcome [7] 0 0
Plasma Concentration of TAK-101 After Each Dose
Assessment method [7] 0 0
Timepoint [7] 0 0
Predose and postdose at Weeks 0, 1 and 24
Secondary outcome [8] 0 0
Serum Concentration of Antidrug Antibody (ADAs) to Various Doses of TAK-101
Assessment method [8] 0 0
ADA includes deamidated gliadin peptide- immunoglobulin G (DGP- IgG).
Timepoint [8] 0 0
Predose at Week 1 and before gluten challenge at Weeks 2, 14, 20, and 24

Eligibility
Key inclusion criteria
1. Biopsy-confirmed CeD that is well-controlled, defined as mild or with no ongoing signs or symptoms felt to be related to active CeD and with immunoglobulin A (IgA) tissue transglutaminase (tTG) <2 × upper limit of normal (ULN) and IgG deamidated gliadin peptide (DGP) <3 × ULN.

Note: Participants may be retested for IgA tTG and IgG DGP to meet eligibility criteria at the discretion of the investigator. Intermittent symptoms would not exclude participants from participation as long as symptoms are generally well controlled in the opinion of the investigator, and as long as symptoms are back to baseline for 2 weeks before the run-in gluten challenge.
2. Must be able to maintain a gluten-free diet (GFD) for =6 months.
3. Must be HLA-DQ2.5 and/or HLA-DQ8 positive during screening laboratory testing.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has received any investigational compound within 12 weeks (84 days) or 5 half-lives, whichever is longer, before signing of the informed consent form (ICF).
2. Has received TAK-101 in a previous clinical study.
3. Has presence of other inflammatory gastrointestinal (GI) disorders or systemic autoimmune diseases, that either have the potential to cause persistent GI symptoms similar to CeD or are not well controlled without the use of excluded medications.

* Examples of conditions that are exclusionary include: inflammatory bowel disease, eosinophilic gastroenteritis or colitis, and microscopic colitis requiring treatment in the 6 months before screening.
* Examples of conditions that may be permissible after discussion with the medical monitor/or sponsor include: systemic autoimmune disease such as scleroderma, psoriatic or rheumatoid arthritis, lupus that is stable and without GI involvement, well controlled autoimmune thyroid disease, well controlled type 1 diabetes or proton pump inhibitor -responsive eosinophilic esophagitis in symptomatic and histologically confirmed remission.
4. Has known or suspected refractory CeD or ulcerative jejunitis.
5. Has known or suspected allergy to wheat, such as hypersensitivity and/or anaphylaxis including wheat-dependent-exercise induced anaphylaxis (WDEIA). If there is a possible history of urticaria, angioedema, or anaphylaxis to wheat, investigators should perform testing for wheat anti-Immunoglobulin (anti-IgE) antibodies or refer to an allergist for evaluation prior to enrollment to rule out any of these allergies.
6. Ongoing systemic immunosuppressant, systemic (oral or IV) corticosteroid treatment, or has received treatment with systemic immunosuppressants or corticosteroids in the 12 weeks before run-in gluten challenge.
7. Has known or suspected clinically significant liver disease or positive test result for hepatitis B or C.
8. Has intolerable symptoms after the run-in gluten challenge and is unwilling to undergo subsequent post treatment gluten challenges.
9. Has known allergy to or intolerance of TAK-101 or any of its ingredients or excipients. Also, any subject with a symptomatic allergic reaction that is confirmed by laboratory serology such as elevated tryptase levels following the administration of TAK-101 will be excluded from future dosing.
10. Has a current diagnosis of active malignancy or malignancy diagnosed in the 5 years prior to screening or is receiving ongoing treatment for malignancy.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
AUNSQLD,VIC,WA
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [2] 0 0
Emeritus Research, Sydney - Botany
Recruitment hospital [3] 0 0
Coral Sea Clinical Research Institute - North Mackay
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Emeritus Research, Melbourne - Camberwell
Recruitment hospital [6] 0 0
The Northern Hospital - Epping
Recruitment hospital [7] 0 0
St John of God Midland - Midland
Recruitment hospital [8] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [9] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment postcode(s) [1] 0 0
VIC 3050 - Parkville
Recruitment postcode(s) [2] 0 0
NSW 2019 - Botany
Recruitment postcode(s) [3] 0 0
QLD 4740 - North Mackay
Recruitment postcode(s) [4] 0 0
QLD 4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
VIC 3124 - Camberwell
Recruitment postcode(s) [6] 0 0
VIC 3076 - Epping
Recruitment postcode(s) [7] 0 0
6056 - Midland
Recruitment postcode(s) [8] 0 0
VIC 3065 - Fitzroy
Recruitment postcode(s) [9] 0 0
QLD 4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
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California
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United States of America
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Colorado
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
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New Mexico
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United States of America
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New York
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North Carolina
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United States of America
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Rhode Island
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United States of America
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Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
New Zealand
State/province [22] 0 0
AU
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New Zealand
State/province [23] 0 0
OT
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New Zealand
State/province [24] 0 0
WG
Country [25] 0 0
New Zealand
State/province [25] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Takeda Contact
Address 0 0
Country 0 0
Phone 0 0
+1-877-825-3327
Email 0 0
medinfoUS@takeda.com
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.