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

Inclusion Criteria:

1. Biopsy-confirmed CeD that is well-controlled, defined as mild or with no ongoingsigns 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 deamidatedgliadin peptide (DGP) <3 × ULN. Note: Participants may be retested for IgA tTG and IgG DGP to meet eligibilitycriteria at the discretion of the investigator. Intermittent symptoms would notexclude participants from participation as long as symptoms are generally wellcontrolled in the opinion of the investigator, and as long as symptoms are back tobaseline for 2 weeks before the run-in gluten challenge.

2. Must be able to maintain a gluten-free diet (GFD) for ≥6 months.

3. Must be HLA-DQ2.5 and/or HLA-DQ8 positive during screening laboratory testing.

Exclusion Criteria:

1. 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).

2. Has received TAK-101 in a previous clinical study.

3. Has presence of other inflammatory gastrointestinal (GI) disorders or systemicautoimmune diseases, that either have the potential to cause persistent GI symptomssimilar to CeD or are not well controlled without the use of excluded medications.

• Examples of conditions that are exclusionary include: inflammatory boweldisease, eosinophilic gastroenteritis or colitis, and microscopic colitisrequiring treatment in the 6 months before screening.

• Examples of conditions that may be permissible after discussion with themedical monitor/or sponsor include: systemic autoimmune disease such asscleroderma, psoriatic or rheumatoid arthritis, lupus that is stable andwithout GI involvement, well controlled autoimmune thyroid disease, wellcontrolled type 1 diabetes or proton pump inhibitor -responsive eosinophilicesophagitis in symptomatic and histologically confirmed remission.

4. Has known or suspected refractory CeD or ulcerative jejunitis.

5. Has known or suspected allergy to wheat, such as hypersensitivity and/or anaphylaxisincluding wheat-dependent-exercise induced anaphylaxis (WDEIA). If there is apossible history of urticaria, angioedema, or anaphylaxis to wheat, investigatorsshould perform testing for wheat anti-Immunoglobulin (anti-IgE) antibodies or referto an allergist for evaluation prior to enrollment to rule out any of theseallergies.

6. 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.

7. Has known or suspected clinically significant liver disease or positive test resultfor hepatitis B or C.

8. Has intolerable symptoms after the run-in gluten challenge and is unwilling toundergo subsequent post treatment gluten challenges.

9. Has known allergy to or intolerance of TAK-101 or any of its ingredients orexcipients. Also, any subject with a symptomatic allergic reaction that is confirmedby laboratory serology such as elevated tryptase levels following the administrationof TAK-101 will be excluded from future dosing.

10. Has a current diagnosis of active malignancy or malignancy diagnosed in the 5 yearsprior to screening or is receiving ongoing treatment for malignancy.