Inclusion Criteria:

1. Has an adequate comprehension of a gluten-free diet (GFD) assessed by the site investigator after review of responses to a knowledge test. The final determination of a participant's adequate comprehension of a GFD is at the discretion of the investigator. 2. Has at least 1 CeD-related GI symptom of moderate or greater severity, as measured by the CDSD, on at least 3 days out of any consecutive 7-day period during the screening period (Week -8 visit until Week -4 visit), felt by the investigator to be related to gluten exposure. The CeD-related symptom(s) may vary day by day as long as the severity of at least 1 symptom is moderate or greater. The participants must meet symptom criteria to undergo esophagogastroduodenoscopy (EGD)/video capsule endoscopy (VCE). 3. Has been attempting to maintain a GFD for at least 12 months as self-reported by the participant. 4. Has small intestinal villous atrophy on duodenal biopsy defined as Vh:Cd <2.5 at Week -4. 5. The participant is human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive. 6. The participant is in a good general state of health according to clinical history and physical examination, in the opinion of the investigator. 7. Have a body mass index (BMI) between 16 and 45 kilogram per meter square (kg/m^2), inclusive. Note: Individuals with BMI of 40 to 45 should be discussed with the medical monitor and confirmed to be appropriate for endoscopy according to local site guidelines. 8. The participant is willing and able to continue any current dietary and/or medical regimens (including gastric acid suppression) in effect at the first visit (Visit 1). There should be no changes to diet, medications (prescription or over-the-counter) or supplements during study participation.

Exclusion Criteria:

1. Has the presence of other inflammatory GI disorders or systemic autoimmune diseases (including but not limited to the following: inflammatory bowel disease, eosinophilic esophagitis, gastroenteritis or colitis, microscopic colitis diagnosed at screening or requiring treatment in the 6 months before screening, scleroderma, psoriatic or rheumatoid arthritis, lupus) other than those noted below:

• - Thyroid disease that has been well-controlled for at least 6 months.

• - Well-controlled type 1 diabetes (glycosylated hemoglobin <8% and no hospitalization or emergency room visit in the last 12 months for hyperglycemia or hypoglycemia).

2. Has ongoing systemic immunosuppressant, systemic corticosteroid treatment excluding medication given for the endoscopies, or treatment with systemic immunosuppressants or systemic corticosteroids in the 12 weeks before Screening. • The participant is receiving immunosuppressive doses of corticosteroids: 3 mg per day or more of budesonide for more than 3 consecutive days within 3 months before Screening, more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months before the first dose, any dose of oral or intravenous (IV) corticosteroids within 30 days of the first dose, or high-dose inhaled corticosteroids (>960 micrograms per day [μg/day] of beclomethasone dipropionate or equivalent), or other systemic immunosuppressive agents. 3. Has ongoing use of over-the-counter digestive enzymes or digestive supplements, other than lactase, including those for gluten digestion. Probiotics are allowable if they were started before Screening and not discontinued or changed in dose or type during the study. 4. Has completed the CDSD on ≤75% of the evaluable days during the run-in period until randomization. 5. Has active microscopic colitis requiring treatment in the 6 months before Screening. • Microscopic colitis detected at screening if sigmoidoscopy is performed would exclude the participant. 6. Has known or suspected type 2 refractory CeD or ulcerative jejunitis. 7. Has ongoing chronic use (defined as >7 days continuous use) of a nonsteroidal anti-inflammatory drug aside from <100 mg aspirin, daily, for prophylactic use. 8. Has ongoing use, or use in the 3 months before screening, of medications known to cause villous abnormalities (e.g., mycophenolate mofetil, angiotensin receptor blockers, colchicine). 9. Has used treatments for GI symptoms including antiemetics, antidiarrheals, antispasmodics, medical marijuana, (use of medical marijuana indicated for non-GI conditions is not exclusionary) within 2 weeks of Screening and during the run-in period. Participants on stable dose (i.e., more than 4 weeks) of an osmotic, bulking-forming or emollient (surface active agent) laxative are eligible, provided symptoms are considered not related to CeD in the opinion of the investigator. 10. Has a known or suspected severe enteric infection (viral, bacterial, or parasitic) within 6 months before randomization. Severe enteric infection is defined as requiring emergency room visit or hospitalization or treatment with antibiotics or anti-infectives due to infection. Non enteric viral infections, either resolved or well-controlled are not exclusionary. 11. Has a contraindication to endoscopy with duodenal biopsy. --Contraindication to VCE (strictures, anastomoses, etc) is not an exclusion if the participant is able to complete the other aspects of the study. 12. Has additional food allergies (tapioca syrup, oats, almonds, rice crisp, chocolate, almond, butter, wheat gluten, cocoa butter, oat flour, glycerin, sunflower lecithin, salt, and natural flavors) to nongluten ingredients in the SIGE bar study food or significant symptoms upon ingestion of the gluten-free SIGE bar during screening. 13. Has a history of intolerance, hypersensitivity, or idiosyncratic reaction to an aminoglycoside. 14. Has a known human immunodeficiency virus (HIV) infection or positive tests for hepatitis B or C. The participant has a known clinically significant chronically active hepatopathy of any origin, including cirrhosis, and participants with persistent positive hepatitis B virus surface antigen and quantitative hepatitis B virus polymerase chain reaction (PCR), or positive serology for hepatitis C virus (HCV) and quantitative HCV PCR within 6 months before the screening visit. 15. Is positive for severe acute respiratory syndrome coronavirus 2 at the time of screening and exhibits symptoms that, in the opinion of the investigator, may interfere with study compliance, completion, or accurate assessment of study outcomes or safety. 16. Has a known hypersensitivity reaction and/or allergy, including anaphylaxis, to wheat and/or gluten. 17. Has known history of hypersensitivity, idiosyncratic reaction, or intolerance to any ingredients or excipients in TAK-062 and/or placebo. Region-specific

Exclusion Criteria:

18. Participant enrolling in a study in France is not affiliated to a social security scheme or a beneficiary of such a scheme. 19. Participant enrolling in a study in France is deprived of their liberty by a judicial or administrative decision.

The drug being tested in this study is called TAK-062. TAK-062 is designed to break down gluten in the stomach and is being tested to treat people who have active CeD, attempting to maintain a GFD. The study will enroll approximately 377 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in Cohort 1: 1. Cohort 1 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar and Gluten-free SIGE Bar. 2. Cohort 1 (Age 18 and older): TAK-062 Dose 1 + SIGE Gluten-Bar and Gluten-free SIGE Bar. After the interim analysis, Cohort 1 data will be reviewed by an external independent data monitoring committee (DMC), and based on the Sponsor's decision, adolescent participants will be enrolled in Cohort 2. Adult participants, 18 years and older will be enrolled into Cohort 2 once Cohort 1 has completed enrolment. Adult participants will be randomly assigned to one of the five study drug and SIGE treatment groups (Groups a-e), and approximately 21 adolescent participants will be enrolled and randomly assigned to Groups d, e, and f (adolescents only). Adolescents in Cohort 2 will receive only gluten-free SIGE bars. 1. Cohort 2 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar and Gluten-free SIGE Bar. 2. Cohort 2 (Age 18 and older): TAK-062 Dose 2 + SIGE Gluten-Bar and Gluten-free SIGE Bar. 3. Cohort 2 (Age 18 and older): TAK-062 Dose 3 + SIGE Gluten-Bar and Gluten-free SIGE Bar. 4. Cohort 2 (Age 12 and older): TAK-062 Placebo + Gluten-free SIGE Bar. 5. Cohort 2 (Age 12 and older): TAK-062 Dose 1 + Gluten-free SIGE Bar. 6. Cohort 2 (Age 12-17): TAK-062 Dose 2 + Gluten-free SIGE Bar. This multi-center trial will be conducted in the United States (US), Canada, United Kingdom and the European Union. The overall time to participate in this study is approximately 36 weeks.

Arms

Placebo Comparator: Cohort 1: TAK-062 Placebo + SIGE Gluten-Bar and Gluten-free SIGE Bar

TAK-062 placebo-matching 4 tablets, orally, taken within pre-determined time before the start of a meal and SIGE gluten bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks. Participants also receive gluten-free bar during the run-in period.

Experimental: Cohort 1: TAK-062 Dose 1 + SIGE Gluten-Bar and Gluten-free SIGE Bar

TAK-062 Dose 1, 4 tablets, orally, taken within pre-determined time before the start of a meal and SIGE gluten bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks. Participants also receive gluten-free bar during the run-in period.

Placebo Comparator: Cohort 2: TAK-062 Placebo + SIGE Gluten-Bar and Gluten-free SIGE Bar

TAK-062 placebo-matching 4 tablets, orally, taken within pre-determined time before the start of a meal and SIGE gluten and gluten free bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Experimental: Cohort 2: TAK-062 Dose 2 + SIGE Gluten-Bar and Gluten-free SIGE Bar

TAK-062 Dose 2, 4 tablets, orally, taken within pre-determined time before the start of a meal and SIGE gluten and gluten free bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Experimental: Cohort 2: TAK-062 Dose 3 + SIGE Gluten-Bar and Gluten-free SIGE Bar

TAK-062 Dose 3, 4 tablets, orally, taken within pre-determined time before the start of a meal and SIGE gluten and gluten free bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Placebo Comparator: Cohort 2: TAK-062 Placebo + Gluten-free SIGE Bar

TAK-062 placebo-matching 4 tablets, orally, taken within pre-determined time before the start of a meal and gluten-free SIGE bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Experimental: Cohort 2: TAK-062 Dose 1 + Gluten-free SIGE Bar

TAK-062 Dose 1, 4 tablets, orally, taken within pre-determined time before the start of a meal and gluten-free SIGE bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Experimental: Cohort 2: TAK-062 Dose 2 + Gluten-free SIGE Bar

TAK-062 4 tablets, orally, taken within pre-determined time before the start of a meal and gluten-free SIGE bar, orally, with a meal, at protocol defined timepoints, for up to 24 weeks.

Interventions

Drug: - TAK-062

TAK-062 tablets.

Dietary Supplement: - Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar

SIGE gluten bars.

Drug: - TAK-062 Placebo

TAK-062 placebo-matching tablets.

Dietary Supplement: - Simulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar

SIGE gluten-free bars.