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

NCT04530123 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: TAK-101-2001U1111-1253-8169
• Study Type: interventional
• Target: 102
• Locations: 4 countries
• Sites: 48

Brief Summary

The main aim of the study is to assess if TAK-101 can reduce gluten related symptoms and immune activation in adult participants with celiac disease (CeD) on a gluten-free diet (GFD). Participants will receive TAK-101 and/or placebo through the vein on Day 1 and Day 8. All participants will receive active treatment at Week 24.

Conditions

Celiac Disease

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20)

Secondary Outcomes (8)

• Percentage of Participants Experiencing at Least One Adverse Event (AE) and Adverse Events of Special Interest (AESIs)

  From the first IV dose up to 30 days after last IV dose (Up to Week 28)

• 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)

  Run-in (Visit 2), Weeks 8, 14, and 20

• 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

  Run-in (Visit 2), Weeks 8, 14, and 20

• 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

  Run-in (Visit 2), Weeks 8, 14, and 20

• Fold Change in Plasma Interleukin-2 (IL-2) from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20

  Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20

Study Arms (7)

Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE

EXPERIMENTAL

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.

Drug: Placebo; Drug: TAK-101; Dietary Supplement: Gluten

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

EXPERIMENTAL

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.

Drug: Placebo; Drug: TAK-101; Dietary Supplement: Gluten

Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE

EXPERIMENTAL

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.

Drug: TAK-101; Dietary Supplement: Gluten

Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE

EXPERIMENTAL

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.

Drug: Placebo; Drug: TAK-101; Dietary Supplement: Gluten

Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE

EXPERIMENTAL

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.

Drug: TAK-101; Dietary Supplement: Gluten

Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE

EXPERIMENTAL

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.

Drug: Placebo; Drug: TAK-101; Dietary Supplement: Gluten

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

EXPERIMENTAL

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.

Drug: TAK-101; Dietary Supplement: Gluten

Interventions

Placebo DRUG

TAK-101 placebo-matching intravenous infusion

Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE; Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE

TAK-101 DRUG

TAK 101 intravenous infusion

Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE; Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE; Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE; Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE; 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

Gluten DIETARY_SUPPLEMENT

Powder form (vital wheat gluten)

Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE; Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE; Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE; Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE; Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE; 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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Must be able to maintain a gluten-free diet (GFD) for ≥6 months.
• Must be HLA-DQ2.5 and/or HLA-DQ8 positive during screening laboratory testing.

You may not qualify if:

• 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).
• Has received TAK-101 in a previous clinical study.
• 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 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.
• Has known or suspected refractory CeD or ulcerative jejunitis.
• 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.
• 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.
• Has known or suspected clinically significant liver disease or positive test result for hepatitis B or C.
• Has intolerable symptoms after the run-in gluten challenge and is unwilling to undergo subsequent post treatment gluten challenges.
• 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.
• Has a current diagnosis of active malignancy or malignancy diagnosed in the 5 years prior to screening or is receiving ongoing treatment for malignancy.

Sponsors & Collaborators

• Takeda: lead

Study Sites (48)

One of a Kind Clinical Research Center LLC

Scottsdale, Arizona, 85258, United States

Location

Gastroenterology and Liver Institute

Escondido, California, 92025, United States

Location

Cadena Care Institute, Inc.

Poway, California, 92064, United States

Location

Asthma and Allergy Associates, PC

Colorado Springs, Colorado, 80907, United States

Location

GCP Clinical Research, LLC

Tampa, Florida, 33609, United States

Location

Agile Clinical Research Trials

Atlanta, Georgia, 30328, United States

Location

Lemah Creek Clinical Research

Burr Ridge, Illinois, 60527, United States

Location

Gastroenterology Associates, PA

Rockford, Illinois, 61107, United States

Location

Rockford Gastroenterology Associates, Ltd.

Rockford, Illinois, 61107, United States

Location

Berkshire Medical Center

New Albany, Indiana, 47150, United States

Location

Gastroenterology Health Partners, PLLC

New Albany, Indiana, 47150, United States

Location

Boston Specialists

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Berkshire Medical Center, Inc.

Pittsfield, Massachusetts, 01201, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48048, United States

Location

Wellness Clinical Research

Chesterfield, Michigan, 48048, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, 87102, United States

Location

Basil Clinical

Inwood, New York, 11096, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center. New York Presbyterian Hospital

New York, New York, 10032, United States

Location

East Carolina Gastroenterology, PA

Jacksonville, North Carolina, 28546, United States

Location

GI Alliance-Rhode Island

Providence, Rhode Island, 02904, United States

Location

Amel Med LLC

Georgetown, Texas, 78628, United States

Location

Care Access Research - Salt Lake City

Ogden, Utah, 84403, United States

Location

Royal Melbourne Hospital

Parkville, AU, VIC 3050, Australia

Location

Emeritus Research, Sydney

Botany, NS, NSW 2019, Australia

Location

Coral Sea Clinical Research Institute

North Mackay, Queensland, QLD 4740, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, QLD 4102, Australia

Location

Emeritus Research, Melbourne

Camberwell, Victoria, VIC 3124, Australia

Location

The Northern Hospital

Epping, Victoria, VIC 3076, Australia

Location

St John of God Midland

Midland, Western Australia, 6056, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, VIC 3065, Australia

Location

Mater Hospital Brisbane

South Brisbane, QLD 4101, Australia

Location

Gastroenterology and Internal Medicine Research Institute (GIRI)

Edmonton, Alberta, T5R 1W2, Canada

Location

PerCuro Clinical Research Ltd.

Victoria, British Columbia, V8V 3M9, Canada

Location

McMaster University

Hamilton, Ontario, L8S4K1, Canada

Location

Scott Shulman Medicine Professional Corporation

North Bay, Ontario, P1B 2H3, Canada

Location

DIEX Recherche Quebec Inc.

Québec, Quebec, G1V 4T3, Canada

Location

Silverdale Medical

Silverdale, Auckland, 930, New Zealand

Location

Optimal Clinical Trials - North

Auckland, AU, 632, New Zealand

Location

Southern Clinical Trials Totara

New Lynn, AU, 1016, New Zealand

Location

Momentum Clinical Research Dunedin

Dunedin, OT, 90160, New Zealand

Location

P3 Research Limited (Wellington)

Wellington, OT, 6021, New Zealand

Location

Capital, Coast and Hutt Valley - Wellington Regional Hospital

Boulcott, WG, 5010, New Zealand

Location

Lakeland Clinical Trials Wellington

Upper Hutt, WG, 5018, New Zealand

Location

Optimal Clinical Trials - Central

Grafton, 1010, New Zealand

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
• Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.

MeSH Terms

Conditions

Celiac Disease

Interventions

Glutens

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: August 28, 2020
• Study Start: June 23, 2022
• Primary Completion: December 9, 2025
• Study Completion: January 8, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

NZ (8); AU (9); CA (5); US (26)