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 2 cohorts planned. Cohort 1 has 1 dose level and the Cohort 2 may include 1 or 2 additional dose levels, depending on safety, tolerability, and activity observed in Cohort 1. Dosing in the Cohort 2 will be based on data from Cohort 1.

The study will enroll approximately 90 patients. In Cohort 1, 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 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 micrograms per kilogram (µg/kg) Gluten Epitopes (GE) TAK-101 at Week 24.

Group B: 1 infusion dose of 25 µg/kg GE TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.

Group C: 2 infusion doses of 25 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.

If it is deemed appropriate to enroll both the TAK-101 50 µg/kg GE and the 12.5 µg/kg GE dose levels in Cohort 2, approximately 45 participants may be randomly assigned in 1:2:2 ratio in Cohort 2 to receive:

Group A: Two infusion doses of placebo, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.

Group D: Two infusion doses of 50 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 50 µg/kg GE TAK-101 at Week 24.

Group F: Two infusion doses of 12.5 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg GE TAK-101 at Week 24.

If it is decided not to open the second cohort at the 50 µg/kg GE dose level and if 1 2.5 µg/kg GE dose is recommended to be tested by the independent data monitoring committee (IDMC), approximately 27 participants will be randomly assigned in 1:2 ratio to receive:

Group E: Two infusion doses of placebo, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg GE TAK-101 at Week 24.

Group F: Two infusion doses of 12.5 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg TAK-101 at Week 24.

This trial will be conducted globally. The overall time to participate in this study is approximately 34 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	90 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 25 µg/kg GE 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 TAK-101 placebo-matching intravenous infusion Drug: TAK-101 Dietary Supplement: Gluten
Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE 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 TAK-101 placebo-matching intravenous infusion 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 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 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 TAK-101 placebo-matching intravenous infusion 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 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 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 TAK-101 placebo-matching intravenous infusion 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 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

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-DQ2.5-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) and Adverse Events of Special Interest (AESIs) [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. An AESI (serious or nonserious) is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate.
2. 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]
   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 prior and after the respective gluten challenge.
3. 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]
   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 prior and following gluten challenge at Weeks 8, 14, and 20.
4. 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]
   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. GI symptom severity score ranges from 0 to 20 with higher score indicating more severe disease.
5. 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]
   The pre-/post-gluten challenge fold change in plasma IL-2 from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20 will be compared.
6. Fold Change in Plasma IL-2 at Specified Time Points [Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20]
   The pre-/post-gluten challenge fold change in plasma IL-2 at each of the time points will be compared.
7. Plasma Concentration of TAK-101 After Each Dose [Predose and postdose at Weeks 0, 1 and 24]
8. Serum Concentration of Antidrug Antibody (ADAs) to Various Doses of TAK-101 [Predose at Week 1 and before gluten challenge at Weeks 2, 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 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.
Exclusion Criteria	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 are exclusionary include: inflammatory bowel disease, eosinophilic gastroenteritis or colitis, and microscopic colitis requiring treatment in the 6 months before screening. 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.

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

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Additional Information

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Additional Relevant MeSH Terms

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