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
Celiac Disease	Drug: Placebo Drug: TAK-101 Dietary Supplement: Gluten

Study Design

Study Type	Interventional
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

Group/ Cohort	Intervention/ Treatment
Cohort 1, Group A: Placebo + Placebo + TAK-101 2 mg/kg 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 2 milligram per kilogram (mg/kg) will be given 23 weeks after the second dose at approximately Week 24.	Drug: Placebo TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 1, Group B: TAK-101 2 mg/kg + Placebo + TAK-101 2 mg/kg 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. A third IV infusion dose of TAK-101 2 mg/kg will be given 23 weeks after the second dose at approximately Week 24.	Drug: Placebo TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 1, Group C: TAK-101 2 mg/kg + TAK-101 2 mg/kg + TAK-101 2 mg/kg Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 2 mg/kg 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 2 mg/kg will be given 23 weeks after the second dose at approximately Week 24.	Drug: TAK-101 Dietary Supplement: Gluten
Cohort 2, Group D: Placebo + Placebo + TAK-101 2 mg/kg 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 2 mg/kg 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 TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 2, Group E: TAK-101 4 mg/kg + Placebo + TAK-101 4 mg/kg 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. A third IV infusion dose of TAK-101 4 mg/kg 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 TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 2, Group F: TAK-101 4 mg/kg + TAK-101 4 mg/kg + TAK-101 4 mg/kg Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 4 mg/kg 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 4 mg/kg 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 G: TAK-101 1 mg/kg + TAK-101 1 mg/kg + TAK-101 1 mg/kg Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 1 mg/kg 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 1 mg/kg will be given 23 weeks after the second dose at approximately Week 24 (1 mg/kg may not be needed based on review of Cohort 1 data). Cohort 2 would start based on the results of Cohort 1.	Drug: TAK-101 Dietary Supplement: Gluten
Cohort 2, Group D: Placebo + Placebo + TAK-101 1 mg/kg 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 1 mg/kg 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 the second cohort at the 4 mg/kg dose level i.e. if 4mg/kg Groups E and F are not opened.	Drug: Placebo TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 2, Group E: TAK-101 1 mg/kg + Placebo + TAK-101 1 mg/kg Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 1 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. A third IV infusion dose of TAK-101 1 mg/kg 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 the second cohort at the 4 mg/kg dose level i.e. if 4mg/kg Groups E and F are not opened.	Drug: Placebo TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.
2. 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.
3. 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.
4. 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.
5. Plasma Concentration of TAK-101 After Each Dose [Predose and postdose at Weeks 0, 1 and 24]
6. 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)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	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 attempting to maintain a gluten-free diet (GFD) for ≥6 months. Must be HLA-DQ2 and/or HLA-DQ8 positive during screening laboratory testing.
Exclusion Criteria	Has received any investigational compound within 12 weeks (84 days) before signing of the informed consent or during the current study. Has received TAK-101 (TIMP-GLIA) in a previous clinical study or as a therapeutic agent. 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). Has known or suspected refractory CeD or ulcerative jejunitis. Has additional food allergies or intolerances that prevent participation in the food challenge. 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. Has known or suspected chronic liver disease or positive for hepatitis B or C. Has intolerable symptoms after the run-in gluten challenge and is unwilling to undergo subsequent posttreatment gluten challenges.

Contacts and Locations

Sponsors and Collaborators	Takeda
Locations	University of Alabama at Birmingham | Birmingham, Alabama, United States, 35233 One of a Kind Clinical Research Center LLC | Scottsdale, Arizona, United States, 85258 Precision Research Institute, LLC | Chula Vista, California, United States, 91910 Gastroenterology and Liver Institute | Escondido, California, United States, 92025 Care Access Research Los Gatos | Los Gatos, California, United States, 95032 California Medical Research Associates Inc. | Northridge, California, United States, 91324 Asthma and Allergy Associates, PC | Colorado Springs, Colorado, United States, 80907 Gastro Florida | Clearwater, Florida, United States, 33756 Sweet Hope Research Specialty, Inc. | Hialeah, Florida, United States, 33016 Wellness Clinical Research | Miami Lakes, Florida, United States, 33016 GCP Clinical Research, LLC | Tampa, Florida, United States, 33609 Agile Clinical Research Trials | Atlanta, Georgia, United States, 30328 Lemah Creek Clinical Research | Oakbrook Terrace, Illinois, United States, 60181 Rockford Gastroenterology Associates, Ltd. | Rockford, Illinois, United States, 61107 Gastroenterology Health Partners, PLLC | New Albany, Indiana, United States, 47150 University Medical Center New Orleans | New Orleans, Louisiana, United States, 70112 Boston Specialists | Boston, Massachusetts, United States, 02111 Beth Israel Deaconess Medical Center | Boston, Massachusetts, United States, 02215 Lahey Clinic Inc. - PARENT ACCOUNT | Burlington, Massachusetts, United States, 01805 Berkshire Medical Center | Pittsfield, Massachusetts, United States, 01201 Berkshire Medical Center | Pittsfield, Massachusetts, United States, 01201 Clinical Research Institute of Michigan, LLC | Chesterfield, Michigan, United States, 48047 Clinical Research Institute of Michigan, LLC | Chesterfield, Michigan, United States, 48047 Revive Research Institute | Farmington Hills, Michigan, United States, 48334 Revive Research Institute | Farmington Hills, Michigan, United States, 48334 Mayo Clinic - Rochester | Rochester, Minnesota, United States, 55905 Albuquerque Clinical Trials, Inc. | Albuquerque, New Mexico, United States, 87102 Columbia University | New York, New York, United States, 10032 Javara Inc | Charlotte, North Carolina, United States, 28210 Medication Management, LLC | Greensboro, North Carolina, United States, 27408 East Carolina Gastroenterology, PA | Jacksonville, North Carolina, United States, 28546 Wellnow Urgent Care and Research | Cincinnati, Ohio, United States, 45215 Gastro Health Research | Cincinnati, Ohio, United States, 45219 Cleveland Clinic - Gastroenterology and Hepatology | Cleveland, Ohio, United States, 44195 Penn State University Milton S. Hershey Medical Center | Hershey, Pennsylvania, United States, 17033 University Gastroenterology | Providence, Rhode Island, United States, 02905 MUSC Department of Gastroenterology | Charleston, South Carolina, United States, 29425 Gastroenterology Associates, PA | Greenville, South Carolina, United States, 29607 Vanderbilt University Medical Center | Nashville, Tennessee, United States, 37212-1610 Vanderbilt University Medical Center | Nashville, Tennessee, United States, 37212 Amel Med LLC | Austin, Texas, United States, 78750 Advanced Gastroenterology Associates, PA. | Decatur, Texas, United States, 76234 Biopharma Informatic, LLC | Houston, Texas, United States, 77043 Biopharma Informatic, LLC | Katy, Texas, United States, 77450 GI Alliance - Webster | Webster, Texas, United States, 77598-4080 Clinical Research Partners, LLC | Richmond, Virginia, United States, 23220 Clinical Research Partners, LLC | Richmond, Virginia, United States, 23226 University of Washington | Seattle, Washington, United States, 98195 Bankstown-Lidcombe Hospital | Bankstown, New South Wales, Australia, 2200 Emeritus Research, Sydney | Botany, New South Wales, Australia, 2019 Northern Beaches Clinical Research | Brookvale, New South Wales, Australia, 2100 St Vincent's Hospital Melbourne | Darlinghurst, New South Wales, Australia, 2010 Sutherland Shire Clinical Research | Miranda, New South Wales, Australia, 2228 AusTrials St Leonards | St Leonards, New South Wales, Australia, 2065 Wollongong Clinical Research | Wollongong, New South Wales, Australia, 2500 Griffith University Clinical Trial Unit | Gold Coast, Queensland, Australia, 9726 Coastal Digestive Health | Maroochydore, Queensland, Australia, 4558 Mater Hospital Brisbane | South Brisbane, Queensland, Australia, 4101 Princess Alexandra Hospital | Woolloongabba, Queensland, Australia, 4102 Emeritus Research, Melbourne | Camberwell, Victoria, Australia, 3124 Royal Melbourne Hospital | Parkville, Victoria, Australia, 3050 AusTrials Sunshine | St Albans, Victoria, Australia, 3021 Gastroenterology and Internal Medicine Research Institute (GIRI) | Edmonton, Alberta, Canada, T5R 1W2 South Edmonton Gastroenterology | Edmonton, Alberta, Canada, T6W 3G7 (G.I.R.I.) GI Research Institute | Vancouver, British Columbia, Canada, V6Z 2K5 PerCuro Clinical Research Ltd. | Victoria, British Columbia, Canada, V8V 3M9 St. Boniface Hospital Inc. | Winnipeg, Manitoba, Canada, R2H 2A6 Health Sciences Centre Winnipeg | Winnipeg, Manitoba, Canada, R3A 1R9 Queen Elizabeth II Health Sciences Centre | Halifax, Nova Scotia, Canada, B3H 4K4 Scope Clinic | Brampton, Ontario, Canada, L6C 0C1 McMaster University | Hamilton, Ontario, Canada, L8S 4K1 Centricity Research London Victoria | London, Ontario, Canada, N6A 2C2 Centricity Research Ottawa Greenbelt | Nepean, Ontario, Canada, K2J 4A7 Scott Shulman Medicine Professional Corporation | North Bay, Ontario, Canada, P1B 2H3 The Ottawa Hospital - Riverside Campus | Ottawa, Ontario, Canada, K1H 7W9 The Ottawa Hospital - General Campus | Ottawa, Ontario, Canada, K1H 8L6 Viable Clinical Research | Sudbury, Ontario, Canada, P3C 5K6 Kensington Screening Clinic | Toronto, Ontario, Canada, M5T 3A9 CHUM Centre de Recherche | Montreal, Quebec, Canada, H2X 0A9 CHUM Centre de Recherche | Montreal, Quebec, Canada, H2X 0A9 Montreal General Hospital | Montreal, Quebec, Canada, H3G1A4 Southern Clinical Trials Totara | Auckland, New Zealand, 0600 Optimal Clinical Trials - North | Auckland, New Zealand, 0632 Optimal Clinical Trials - Central | Auckland, New Zealand, 1010 P3 Research Limited (Hawkes Bay) | Havelock North, New Zealand, 3410 Capital, Coast and Hutt Valley District Hutt Hospital | Lower Hutt, New Zealand, 5010 P3 Research Limited (Palmerston North) | Palmerston North, New Zealand, 4414 Lakeland Clinical Trials Wellington | Wellington, New Zealand, 5018 P3 Research Limited (Wellington) | Wellington, New Zealand, 6021
Investigators

More Information

Additional Information

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Additional Relevant MeSH Terms

• Celiac Disease
• Malabsorption Syndromes
• Intestinal Diseases
• Gastrointestinal Diseases
• Digestive System Diseases
• Metabolic Diseases