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History of Changes for Study: NCT04530123
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
Latest version (submitted April 26, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 25, 2020 None (earliest Version on record)
2 September 16, 2020 Study Status and Study Identification
3 April 30, 2021 Study Status
4 September 22, 2021 Study Status, IPDSharing and Contacts/Locations
5 April 26, 2022 Arms and Interventions, Outcome Measures, Study Description, Study Status and Eligibility
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Changes (Merged) for Study: NCT04530123
September 16, 2020 (v2) -- April 30, 2021 (v3)

Changes in: Study Status

Open or close this module Study Identification
Unique Protocol ID: TAK-101-2001
Brief 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
Official 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 IDs: U1111-1253-8169 [Registry Identifier: World Health Organization]
Open or close this module Study Status
Record Verification: September 2020 April 2021
Overall Status: Not yet recruiting
Study Start: April August 29, 2021
Primary Completion: December 2, 2022 [Anticipated]
Study Completion: March 24, 2023 [Anticipated]
First Submitted: August 25, 2020
First Submitted that
Met QC Criteria:
August 25, 2020
First Posted: August 28, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
September 16, 2020 April 30, 2021
Last Update Posted: September 18 May 3, 2020 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Takeda
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The purpose of the study is to compare the number of baseline IFN-γ SFUs to the number of IFN-γ SFUs after a 6-day oral gluten challenge among participants treated with TAK-101 versus placebo.
Detailed Description:

The drug being tested in this study is called TAK-101. TAK-101 is being tested to treat people who have celiac disease. The study has two cohorts planned. The first cohort has 1 dose level and the second cohort may include 1 or 2 dose levels, depending on safety, tolerability, and activity observed in the first cohort.

The study will enroll approximately 108 patients. In the first cohort, approximately 45 participants will be randomly assigned in 1:2:2 ratio in one of the three arm groups -which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). Eligible participants will receive: Cohort 1:

  • Placebo: 2 infusions
  • TAK-101 2 mg/kg: 1 infusion + placebo: 1 infusion
  • TAK-101 2 mg/kg: 2 infusions

All participants will be asked to take TAK-101 intravenous (IV) infusion and TAK-101 placebo matching infusion on Days 1 and 8. After completion of Cohort 1, Cohort 2 may start based on the review of Cohort 1 data by an external data monitoring committee (DMC). Approximately 86 participants may be randomly assigned in 1:2:2:2 ratio in Cohort 2 to receive: Cohort 2 (1 mg/kg may not be needed based on review of Cohort 1 data):

  • Placebo: 2 infusions
  • TAK-101 4 mg/kg : 1 infusion + placebo: 1 infusion
  • TAK-101 4 mg/kg: 2 infusions
  • TAK-101 1 mg/kg: 2 infusions

The TAK-101 1 mg/kg, 2 infusions may be open based on an interim analysis of the cohort 1 Interferon-gamma Spot Forming Units (IFN-γ SFUs) reviewed by the DMC. If TAK-101 1 mg/kg, 2 infusions is not open, approximately 86 participants will be randomly assigned in 1:2:2 ratio to receive:

  • Placebo: 2 infusions
  • TAK-101 1 mg/kg: 1 infusion + placebo: 1 infusion
  • TAK-101 1 mg/kg: 2 infusions

This trial will be conducted in United States and Canada. The overall time to participate in this study is approximately 26 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone OR plus a final visit after receiving their last dose of study drug for a follow-up assessment.

Open or close this module Conditions
Conditions: Celiac Disease
Keywords: Drug Therapy
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 7
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 108 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Placebo Comparator: Cohort 1: Placebo (2 Infusions)
Following a single-day 3 gram (g) oral run-in gluten challenge, participants will receive TAK-101 placebo-matching intravenous (IV) infusion, once 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.
Drug: Placebo
TAK-101 placebo-matching intravenous infusion
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Experimental: Cohort 1: TAK-101 2 mg/kg (1 Infusion) + Placebo (1 Infusion)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 2 mg/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.
Drug: TAK-101
TAK 101 intravenous infusion
Other Names:
  • TIMP-GLIA
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Experimental: Cohort 1: TAK-101 2 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 2 mg/kg IV infusion, once 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.
Drug: TAK-101
TAK 101 intravenous infusion
Other Names:
  • TIMP-GLIA
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Placebo Comparator: Cohort 2: Placebo (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 placebo-matching IV infusion, once 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. Cohort 2 would start based on the results of Cohort 1.
Drug: Placebo
TAK-101 placebo-matching intravenous infusion
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Experimental: Cohort 2:TAK-101 4 mg/kg (1 Infusion)+placebo (1 Infusion)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 4 mg/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. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Names:
  • TIMP-GLIA
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Experimental: Cohort 2: TAK-101 4 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 4 mg/kg IV infusion, once 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. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Names:
  • TIMP-GLIA
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Experimental: Cohort 2: TAK-101 1 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 1 mg/kg IV infusion, once 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. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Names:
  • TIMP-GLIA
Dietary Supplement: Gluten
Powder form (vital wheat gluten)
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change From Baseline in Interferon-gamma Spot Forming Units (IFN-γ SFUs) Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay
[ Time Frame: Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20) ]

IFN-γ SFUs will be measured based on results of a gliadin-specific ELISpot assay using gluten-specific T cells which will be isolated from blood.
Secondary Outcome Measures:
1. Number of Participants with at Least one Adverse Event (AE)
[ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]

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.
2. Number of Participants with Infusion Reaction (IR)
[ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]

3. Number of Participants with Cytokine Release Syndrome (CRS)
[ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]

4. Number of Participants with Markedly Abnormal Vital Sign Values
[ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]

Vital signs will include assessment of body temperature, respiratory rate, blood pressure and pulse.
5. Number of Participants with Markedly Abnormal Laboratory Test Values
[ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]

Clinical laboratory values will include test for hematology, serum chemistry and urinalysis including liver tests.
6. Change From Baseline in Celiac Disease Symptom Diary (CDSD) 3-day Average Score
[ Time Frame: Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20 ]

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.
7. Change From Baseline in CDSD 3-day Peak Score
[ Time Frame: Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20 ]

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.
8. Change From Baseline Pre- to 4 hours Post-gluten Challenge in Plasma Interleukin-2 (IL-2)
[ Time Frame: Baseline to Week 20 ]

9. Plasma Concentration of TAK-101 After the First and Second Dose
[ Time Frame: Predose and postdose at Weeks 0 and 1 ]

10. Change From Baseline in Serum Concentration of Antidrug Antibody (ADAs) to TAK-101
[ Time Frame: Predose and postdose at Weeks 0 and 1 and before gluten challenge at Week 2, 8, 14 and 20 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Biopsy-confirmed celiac disease (CeD) that is well-controlled, defined as mild or with no ongoing signs or symptoms felt to be related to active CeD and with IgA tTG <2 × upper limit of normal (ULN) and IgG DGP <3 × ULN.

    Note: Participants may be retested for IgA tissue transglutaminase (tTG) and IgG deamidated gliadin peptide (DGP) to meet eligibility criteria at the discretion of the investigator.

  2. Must be on a gluten-free diet (GFD) for ≥6 months.
  3. Must be HLA-DQ2 and/or HLA-DQ8 positive during screening laboratory testing.

Exclusion Criteria:

  1. Has received any investigational compound within 12 weeks (84 days) before signing of the informed consent.
  2. Has received TAK-101 (TIMP-GLIA) in a previous clinical study or as a therapeutic agent.
  3. Has presence of inflammatory gastrointestinal disorders or autoimmune diseases, other than well-controlled autoimmune thyroid disease or well-controlled type 1 diabetes mellitus (defined as glycosylated hemoglobin <8 and no hospitalization in the last 12 months for hyper/hypoglycemia).
  4. Has known or suspected refractory CeD or ulcerative jejunitis.
  5. Has additional food allergies or intolerances that prevent participation in the food challenge.
  6. Is receiving 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 chronic liver disease or positive for hepatitis B or C.
Open or close this module Contacts/Locations
Central Contact Person: Takeda Study Registration Call Center
Telephone: +1-877-825-3327
Email: medinfoUS@takeda.com
Study Officials: Medical Director Clinical Science
Study Director
Takeda
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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