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
ClinicalTrials.gov processed this data on May 3, 2024. Link to the current ClinicalTrials.gov record.Recruitment Status
RECRUITING (See Contacts and Locations)Verified May 2024 by Takeda
Sponsor
TakedaInformation Provided by (Responsible Party)
TakedaClinicaltrials.gov Identifier
NCT04530123Other Study ID Numbers: TAK-101-2001
First Submitted: August 25, 2020
First Posted: August 28, 2020
Last Update Posted: May 6, 2024
Last Verified: May 2024
History of Changes
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Study 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. Dosing in the second cohort will be based on data from the initial cohort.The study will enrol approximately 108 patients (18 per arm). 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 in Cohort 1 will receive:
Group A: 2 infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.
Group B: 1 infusion dose of 2 mg/kg of TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.
Group C: 2 infusion doses of 2 mg/kg of TAK-101, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.
After the review of Cohort 1 safety data, a decision will be made to either stop the study or continue the study by the sponsor safety management team (SMT), based on recommendations from independent data monitoring committee (IDMC). If it is deemed appropriate to enroll both the TAK-101 4 mg/kg and 1 mg/kg dose level, approximately 63 participants may be randomly assigned in 1:2:2:2 ratio in Cohort 2 to receive:
Group D: Two infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.
Group E: One infusion dose of 4 mg/kg TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 4 mg/kg TAK-101 at Week 24.
Group F: Two infusion doses of 4mg/kg, 1 on Day 1 and 1 on day 8, followed by 1 infusion dose of 4 mg/kg TAK-101 at Week 24.
Group G: TAK-101 1 mg/kg: Two infusion doses of 1 mg/kg TAK-101, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24 (1 mg/kg may not be needed based on review of Cohort 1 data).
In Cohort 2 if the 1 mg/kg treatment arm is not needed, Cohort 2 will consist of 45 participants in total, being randomized in a 1:2:2 ratio to 1 of the 3 treatment groups (Groups D, E, F) listed above.
If it is decided not to open the second cohort at the 4 mg/kg dose level and if 1 mg/kg dose is recommended to be tested by the IDMC, approximately 45 participants will be randomly assigned in 1:2:2 ratio to receive:
Group D: Two infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.
Group E: One infusion dose of 1 mg/kg TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.
Group F: Two infusion doses of 1 mg/kg, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.
This trial will be conducted in United States and Canada. The overall time to participate in this study is approximately 24 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.
Condition or Disease | Intervention/Treatment |
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Study Design
Study Type | Interventional |
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Anticipated Enrollment | 108 participants |
Design Allocation | Randomized |
Interventional Model | Parallel Assignment |
Masking | Triple |
Primary Purpose | Prevention |
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 |
Study Start Date | June 23, 2022 |
Anticipated Primary Completion Date | October 30, 2025 |
Anticipated Study Completion Date | October 30, 2025 |
Groups and Cohorts
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Outcome Measures
Primary Outcome Measures
- Change From Baseline in Interferon-gamma Spot Forming Units (IFN-γ SFUs) in Human Leukocyte Antigens Density Quotient (HLA-DQ2-positive) Participants Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay [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
- Percentage of Participants Experiencing at Least One Adverse Event (AE), Infusion Related Reaction (IRR), and Cytokine Release Syndrome (CRS) [From the first IV dose up to 30 days after last IV dose (Up to Week 28)] 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. IRR as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5 is defined as disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. CRS as per NCI CTCAE Version 5 is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and shortness of breath caused by the release of cytokines from the cells.
- Change From Baseline in Nausea Severity as Measured by the Celiac Disease Symptom Diary (CDSD) 3-day Average Score [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 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 after the respective gluten challenge. The average score for Day 15 to 20 gluten challenge is the average of the daily scores from the initiation of gluten challenge to 3 days after the last gluten challenge.
- Change From Baseline in CDSD 3-day Peak Nausea Severity Score [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. Peak score is the highest score in the 3 days following gluten challenge starting on the initiation of gluten challenge for challenges at Weeks 8, 14, and 20 and the highest score during and the 3 days following the Day 15-20 gluten challenge.
- Change From Baseline Before Gluten Challenge to 4 hours Post-gluten Challenge in Plasma Interleukin-2 (IL-2) on Day 15 and Weeks 8, 14, and 20 [Baseline, Day 15, Weeks 8, 14, 20] IL-2 levels in the plasma will be tested before and 4 hours after gluten challenge. IL-2 is acutely induced in participants with CeD and detected in the blood within 4 hours.
- Plasma Concentration of TAK-101 After Each Dose [Predose and postdose at Weeks 0, 1 and 24]
- Change From Baseline in Serum Concentration of Antidrug Antibody (ADAs) to TAK-101 [Predose at Weeks 0 and 1 and before gluten challenge at Weeks 2, 8, 14, 20, and 24] ADA includes deamidated gliadin peptide- immunoglobulin G (DGP- IgG).
Eligibility Criteria
Ages Eligible for Study | 18 Years to 75 Years (Adult, Older Adult) |
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Sexes Eligible for Study | All |
Accepts Healthy Volunteers | No |
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Contacts and Locations
Sponsors and Collaborators | Takeda |
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More Information
Additional Information
Additional Relevant MeSH Terms
- Celiac Disease
- Malabsorption Syndromes
- Intestinal Diseases
- Gastrointestinal Diseases
- Digestive System Diseases
- Metabolic Diseases