What side effects are associated with this type of intervention?

Common treatments for Celiac Disease primarily involve a strict gluten-free diet (GFD). For immune modulation therapies similar to TAK-101, which aim to reduce gluten-specific T cell activation, potential side effects may include infusion-related reactions, gastrointestinal symptoms like nausea and diarrhea, and immune-related adverse effects such as increased susceptibility to infections. As with any immune-modulating treatment, monitoring for hypersensitivity reactions and other immune system alterations is crucial.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Celiac Disease that focus on immune modulation similar to TAK-101. The primary management strategy for Celiac Disease remains a strict gluten-free diet. TAK-101 is being studied for its potential to reduce gluten-related symptoms and immune activation in patients with Celiac Disease, representing a novel approach in the treatment landscape.

What other types of research exist?

Promising novel alternatives to TAK-101 for Celiac Disease patients considering treatment in 2024 include T Cell Modulatory Peptide (TCMP-80), which has shown safety and tolerability in early trials, and other immune modulatory therapies under investigation for autoimmune diseases. Additionally, advancements in monoclonal antibodies targeting immune checkpoints like LAG-3, TIM-3, and TIGIT may offer new therapeutic options.

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Immunomodulator

TAK-101 for Celiac Disease

Q: What is the mechanism of action of this treatment?

The primary treatment for Celiac Disease is a strict gluten-free diet, which helps in reducing symptoms and healing intestinal damage by avoiding the ingestion of gluten. However, emerging treatments like TAK-101 focus on immune modulation. TAK-101 aims to reduce gluten-specific T cell activation, which is crucial because the immune response to gluten peptides is what causes the intestinal damage in Celiac Disease. By modulating this immune response, such treatments could potentially allow patients to tolerate small amounts of gluten without triggering severe symptoms, thereby improving their quality of life and reducing the burden of strict dietary adherence.

Phase 2

Recruiting

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must be HLA-DQ2 and/or HLA-DQ8 positive during screening laboratory testing

Must not have

Has known or suspected chronic liver disease or positive for hepatitis B or C

Has known or suspected refractory CeD or ulcerative jejunitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-/post-gluten challenge at run-in (visit 2), day 15, and weeks 8, 14, and 20

Summary

This trial is testing a drug called TAK-101, given through an IV, to help adults with celiac disease who still have symptoms despite following a gluten-free diet. The drug aims to reduce these symptoms by changing how the immune system reacts to gluten. TAK-101 is designed to induce gluten-specific tolerance by encapsulating gluten protein in negatively charged nanoparticles. Participants will receive the drug at different times and doses to see how well it works and how safe it is.

Who is the study for?

Adults with celiac disease who have been on a gluten-free diet for at least 6 months can join. They must test positive for HLA-DQ2 or HLA-DQ8 and have mild or no symptoms of active celiac disease, with certain antibody levels below specified limits. People can't join if they've had certain treatments recently, have refractory celiac disease, other serious health conditions, or can't tolerate gluten challenges.

What is being tested?

The trial is testing TAK-101's ability to prevent immune reactions and symptoms when people with celiac disease eat gluten. Participants will get TAK-101 or a placebo through an IV on two separate days and everyone gets the real treatment after six months.

What are the potential side effects?

Potential side effects are not detailed here but may include reactions related to the infusion process, gastrointestinal discomfort from the gluten challenge, and any immune responses that TAK-101 is designed to mitigate.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My celiac disease is under control with specific blood test levels within the normal range.

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I tested positive for HLA-DQ2 or HLA-DQ8.

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My celiac disease is under control with specific blood test levels within the normal range.

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I tested positive for HLA-DQ2 or HLA-DQ8.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have chronic liver disease or hepatitis B/C.

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I have celiac disease that doesn't respond to a gluten-free diet or I have ulcerative jejunitis.

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I have previously received TAK-101 in a study or as treatment.

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I can't tolerate gluten and refuse more gluten challenges after the first.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-/post-gluten challenge at run-in (visit 2), day 15, and weeks 8, 14, and 20

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-/post-gluten challenge at run-in (visit 2), day 15, and weeks 8, 14, and 20

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-/post-gluten challenge at run-in (visit 2), day 15, and weeks 8, 14, and 20 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline in Interferon-gamma Spot Forming Units (IFN-γ SFUs) in Human Leukocyte Antigens Density Quotient (HLA-DQ2.5-positive) Participants Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay

Secondary study objectives

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

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)

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

+4 more

Trial Design

7Treatment groups

Experimental Treatment

Group I: Cohort 2, Group F: TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GEExperimental Treatment2 Interventions

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.

Group II: Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GEExperimental Treatment3 Interventions

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.

Group III: Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GEExperimental Treatment2 Interventions

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.

Group IV: Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GEExperimental Treatment3 Interventions

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.

Group V: Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GEExperimental Treatment2 Interventions

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.

Group VI: Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GEExperimental Treatment3 Interventions

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.

Group VII: Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GEExperimental Treatment3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gluten

2015

N/A

~330

Placebo

1995

Completed Phase 3

~2670

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The primary treatment for Celiac Disease is a strict gluten-free diet, which helps in reducing symptoms and healing intestinal damage by avoiding the ingestion of gluten. However, emerging treatments like TAK-101 focus on immune modulation. TAK-101 aims to reduce gluten-specific T cell activation, which is crucial because the immune response to gluten peptides is what causes the intestinal damage in Celiac Disease. By modulating this immune response, such treatments could potentially allow patients to tolerate small amounts of gluten without triggering severe symptoms, thereby improving their quality of life and reducing the burden of strict dietary adherence.

In vitro models for gluten toxicity: relevance for celiac disease pathogenesis and development of novel treatment options.