Study Description

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 357 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups in Cohort 1:

Cohort 1 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar

Cohort 1 (Age 18 and older): TAK-062 Dose 1 + SIGE Gluten-Bar

After the interim analysis (IA), 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.

Cohort 2 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar

Cohort 2 (Age 18 and older): TAK-062 Dose 2 + SIGE Gluten-Bar

Cohort 2 (Age 18 and older): TAK-062 Dose 3 + SIGE Gluten-Bar

Cohort 2 (Age 12 and older): TAK-062 Placebo + Gluten-free SIGE Bar

Cohort 2 (Age 12 and older): TAK-062 Dose 1 + Gluten-free SIGE Bar

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.

Condition or Disease	Intervention/Treatment
Celiac Disease	Drug: TAK-062 Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar Drug: TAK-062 Placebo Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar

Study Design

Study Type	Interventional
Actual Enrollment	153 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-062 for the Treatment of Active Celiac Disease in Subjects Attempting a Gluten-Free Diet
Study Start Date	June 30, 2022
Actual Primary Completion Date	November 6, 2024
Actual Study Completion Date	November 6, 2024

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Cohort 1: TAK-062 Placebo + SIGE Gluten-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.	Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar Drug: TAK-062 Placebo
Cohort 1: TAK-062 Dose 1 + SIGE Gluten-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.	Drug: TAK-062 TAK-062 tablets. Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar
Cohort 2: TAK-062 Placebo + SIGE Gluten-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.	Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar Drug: TAK-062 Placebo
Cohort 2: TAK-062 Dose 2 + SIGE Gluten-Bar TAK-062 Dose 2, 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.	Drug: TAK-062 TAK-062 tablets. Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar
Cohort 2: TAK-062 Dose 3 + SIGE Gluten-Bar TAK-062 Dose 3, 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.	Drug: TAK-062 TAK-062 tablets. Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar
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.	Drug: TAK-062 Placebo Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar
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.	Drug: TAK-062 TAK-062 tablets. Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar
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.	Drug: TAK-062 TAK-062 tablets. Dietary Supplement: Simulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar

Outcome Measures

Primary Outcome Measures

1. Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score from Baseline to Week 12 [Baseline (Week -1) to Week 12]
   CDSD GI symptom severity score is an average of the daily GI symptom severity scores during the week. The daily GI symptom severity score is the average of the severity score for diarrhea, abdominal pain, bloating and nausea, ranging from 0 to 4. Symptom severity is evaluated using 5-point Likert-type scales (none, mild, moderate, severe, and very severe). Higher scores indicate severe symptoms.

Secondary Outcome Measures

1. Change in Villous Height to Crypt Depth Ratio (Vh:Cd) from Baseline to Week 24 [Baseline (Week -4, Run-in Period) to Week 24]
   The Vh:Cd ratio represents mucosal architectural changes and a lower Vh:Cd ratio indicates more severe intestinal injury characterized by a flattening of the mucosa.
2. Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Adverse Events (SAEs) and Treatment-Related TEAEs [Up to Week 28]
   Adverse event (AE)= 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. AE can therefore be any unfavorable and unintended sign (e.g., clinically significant abnormal laboratory value, electrocardiogram[ECG] value, or vital sign measurement), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. TEAE=new onset or worsening AEs after the first dose of study treatment regardless of relationship to study drug. SAE= any untoward medical occurrence at any dose that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect, or is an important medical event. TEAEs considered related to the study drug as assessed by the Investigator will be reported.
3. Percentage of Participants with Positive Antidrug Antibodies (ADA) in Serum for TAK-062 [Up to Week 28]
   A positive ADA participant is defined as a participant who has at least 1 positive ADA result during the study and is further categorized as: Transiently positive- defined as participants with confirmed positive ADA in at least 1 sample and no consecutive samples; Persistently positive- defined as participants with confirmed positive ADA in 2 or more consecutive positive ADA samples.

Eligibility Criteria

Ages Eligible for Study	12 Years and Older (Child, Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	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. 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). Has been attempting to maintain a GFD for at least 12 months as self-reported by the participant. Has small intestinal villous atrophy on duodenal biopsy defined as Vh:Cd <2.5 at Week -4. The participant is human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive. The participant is in a good general state of health according to clinical history and physical examination, in the opinion of the investigator. 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. 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	Has the presence of other inflammatory 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 medication. Examples of conditions that are exclusionary include inflammatory bowel disease, eosinophilic esophagitis, gastroenteritis or colitis, microscopic colitis diagnosed at screening or requiring treatment in the 6 months before screening. Examples of conditions that may be permissible after discussion with the medical monitor include systemic autoimmune disease such as scleroderma, psoriatic or rheumatoid arthritis, or lupus that is stable and without GI involvement; well controlled autoimmune thyroid disease; well-controlled type 1 diabetes; or proton pump inhibitor (PPI) responsive eosinophilic esophagitis in symptomatic and histologically confirmed remission. 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 90 days 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. 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. Has completed the CDSD on ≤75% of the evaluable days during the run-in period until randomization. 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. Has known or suspected type 2 refractory CeD or ulcerative jejunitis. 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. 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). 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. 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. 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. 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. Has a history of intolerance, hypersensitivity, or idiosyncratic reaction to an aminoglycoside. 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. 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. Has a known hypersensitivity reaction and/or allergy, including anaphylaxis, to wheat and/or gluten. Has known history of hypersensitivity, idiosyncratic reaction, or intolerance to any ingredients or excipients in TAK-062 and/or placebo. The participant has a current diagnosis of active malignancy or is receiving treatment for active malignancy (hormone therapy alone is not exclusionary). Participants with fully resected Stage 0 (carcinoma in situ) or Stage 1 tumor without signs of recurrence may participate. All other individuals with malignancies diagnosed in the 5 years prior to screening are excluded. Region-specific Exclusion Criteria: Participant enrolling in a study in France is not affiliated to a social security scheme or a beneficiary of such a scheme. Participant enrolling in a study in France is deprived of their liberty by a judicial or administrative decision.

Contacts and Locations

Sponsors and Collaborators	Takeda
Locations	University of Alabama at Birmingham | Birmingham, Alabama, United States, 35233 Research Solutions of Arizona, PC | Litchfield Park, Arizona, United States, 85340 One of a Kind Clinical Research Center LLC | Paradise Valley, Arizona, United States, 85253 Mayo Clinic- Arizona | Scottsdale, Arizona, United States, 85259 GI Alliance- Sun City | Sun City, Arizona, United States, 85351 Adobe Clinical Research LLC | Tucson, Arizona, United States, 85712 Gastroenterology and Liver Institute | Escondido, California, United States, 92025 Om Research LLC | Lancaster, California, United States, 93534 So. California Research Institute Med Group Inc./West Gastroenterology Med Group | Los Angeles, California, United States, 90045 UCLA | Los Angeles, California, United States, 90404 Providence Facey Medical Foundation | Mission Hills, California, United States, 91345 Stanford University School of Medicine | Redwood City, California, United States, 94063 Medical Associates Research Group, Inc. | San Diego, California, United States, 92123 Asthma and Allergy Associates, PC | Colorado Springs, Colorado, United States, 80907 Medical Research Center of Connecticut, LLC 300143562 | Hamden, Connecticut, United States, 06518 Central Connecticut Endoscopy Center | Plainville, Connecticut, United States, 06062 Nature Coast Clinical Research, LLC | Inverness, Florida, United States, 34452 Wellness Clinical Research | Miami Lakes, Florida, United States, 33016 University of Miami Medical Center | Miami, Florida, United States, 33136 Gastroenterology Associates of Pensacola, PA | Pensacola, Florida, United States, 32503 St. Johns Center for Clinical Research | Saint Augustine, Florida, United States, 32086 GCP Clinical Research, LLC | Tampa, Florida, United States, 33609 Agile Clinical Research Trials | Alpharetta, Georgia, United States, 30022 Lemah Creek Clinical Research | Oakbrook Terrace, Illinois, United States, 60181 Indiana University -GI | Indianapolis, Indiana, United States, 46202 University of Iowa Hospital and Clinics | Iowa City, Iowa, United States, 52242 University Medical Center New Orleans | New Orleans, Louisiana, United States, 70112 Massachusetts General Hospital | Boston, Massachusetts, United States, 02114 Beth Israel Deaconess Medical Center | Boston, Massachusetts, United States, 02215 Lahey Hospital and Medical | Burlington, Massachusetts, United States, 01805 Hawthorn Medical Associates LLC | South Dartmouth, Massachusetts, United States, 02747 University of Michigan | Ann Arbor, Michigan, United States, 48109 Clinical Research Institute of Michigan, LLC | Chesterfield, Michigan, United States, 48047 Revive Research Institute, Inc | Farmington Hills, Michigan, United States, 48334 Mayo Clinic - Rochester | Rochester, Minnesota, United States, 55905 Washington University, School of Medicine | Saint Louis, Missouri, United States, 63110 Manhattan Clinical Research, LLC | Manhattan, New York, United States, 10016 New York University Medical Center PRIME | New York, New York, United States, 10016 Blair S Lewis MD | New York, New York, United States, 10032 Rochester Clinical Research | Rochester, New York, United States, 14618 Tryon Medical Partners | Charlotte, North Carolina, United States, 28210 Carolina Digestive Diseases | Greenville, North Carolina, United States, 27834 Gastro Health Research | Cincinnati, Ohio, United States, 45219 Cleveland Clinic - Gastroenterology and Hepatology | Cleveland, Ohio, United States, 44195 Dayton Gastroenterology, Inc | Englewood, Ohio, United States, 45415 Eastern Pennsylvania Gastroeneterology and Liver Specialists | Allentown, Pennsylvania, United States, 18104 Thomas Jefferson University | Philadelphia, Pennsylvania, United States, 19107 Gastroenterology Associates, PA | Greenville, South Carolina, United States, 29607 Rapid City Medical Center, LLC | Rapid City, South Dakota, United States, 57701 Vanderbilt University Medical Center | Nashville, Tennessee, United States, 37232 The Methodist Hospital 150520246 | Houston, Texas, United States, 77030 Biopharma Informatic, LLC | Houston, Texas, United States, 77084 Spring Clinical Research | Houston, Texas, United States, 77090 Biopharma Informatic, LLC | McAllen, Texas, United States, 78503 Victoria Gastroenterology | Victoria, Texas, United States, 77904 University of Virginia Medical Center | Charlottesville, Virginia, United States, 22903 Blue Ridge Medical Research | Lynchburg, Virginia, United States, 24502 Clinical Research Partners, LLC | Richmond, Virginia, United States, 23220 Swedish Gastroenterology | Seattle, Washington, United States, 98104 University of Washington Division of Gastroenterology | Seattle, Washington, United States, 98195 Velocity Clinical Research | Spokane, Washington, United States, 99218 AZ Sint-Lucas | Brugge, Belgium, 8310 AZ Maria Middelares | Gent, Belgium, 9000 Vitaz | Sint-Niklaas, Belgium, 9100 Gastroenterology and Internal Medicine Research Institute (GIRI) | Edmonton, Alberta, Canada, T5R 1W2 St. Boniface Hospital Inc. Section of Nephrology BG 007 | Winnipeg, Manitoba, Canada, R2H 2A6 Kensington Screening Clinic | Toronto, Ontario, Canada, M5T 3A9 McGill University Health Center McGill University | Montreal, Quebec, Canada, H3A 1A1 Hopital Rangueil Service de Gastro Enterologie et Nutrition | Toulouse Cedex 09, Haute Garonne, France, 31059 Institut des MICI | Neuilly, Hauts De Seine, France, 92200 CHU Saint Etienne - Hopital Nord Service de Gastro-Enterologie et Hepatologie | Saint Etienne, Loire, France, 42055 CHU Lille - Hopital Claude Huriez Service des maladies de I'appareil digestif | Lille cedex, Nord, France, 59037 Hopital Europeen Georges Pompidou Gastro Enterologie et Oncologie Digestive | Paris, France, 75015 Azienda Ospedaliero Universitaria di Ferrara | Cona, Ferrara, Italy, 44124 Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico | Milan, Milano, Italy, 20122 Azienda Ospedaliero Universitaria Ospedali Riuniti- Ospedale Pediatrico UOC Pediatria - G. Salesi | Ancona, Italy, 60123 Ospedale Valduce 300205849 | Como, Italy, 22100 Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Internal Medicine | Palermo, Italy, 90127 Fondazione IRCCS Policlinico San Matteo Sezione di Medicina Interna | Pavia, Italy, 27100 Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello) U.O. Gastroenterologia | Pisa, Italy, 56124 Fondazione Policlinico Universitario Agostino Gemelli IRCCS UOC Medicina Interna e Gastroenterologia | Roma, Italy, 168 Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona | Salerno, Italy, 84131 Ospedale Umberto I di Torino S.C. Gastroenterologia | Torino, Italy, 10128 FutureMeds Krakow prev. Krakowskie Centrum Medyczne Sp. z o.o. | Krakow, Poland, 31-501 ALLMEDICA sp. z o. o. | Nowy Targ, Poland, 34-400 Gabinet Lekarski Bartosz Korczowski | Rzeszow, Poland, 35-302 Centrum Medyczne Medyk | Rzeszow, Poland, 35-326 Warsaw IBD Point Profesor Kierkus | Warszawa, Poland, 00-728 Komisja Bioetyczna przy Okregowej Izbie Lekarskiej w Warszawie | Warszawa, Poland, 02-172 Melita Medical SP . Z O. O. | Wroclaw, Poland, 50-449 ETG Zamosc | Zamosc, Poland, 22-400 Vall d'Hebron Research Institute | Barcelona, Spain, 8035 Hospital Universitario Ramon y Cajal Servicio de Gastroenterologia | Madrid, Spain, 28034 Hospital Clinico Universitario Virgen de la Victoria Digestive Service | Malaga, Spain, 29010 Hospital Universitario Virgen Macarena Digestive Service | Sevilla, Spain, 41009 Hospital Universitario Miguel Servet Servicio de Aparato Digestivo | Zaragoza, Spain, 50009 Royal London Hospital Dept of Gastroenterology | London, Greater London, United Kingdom, E1 1FR King's College Hospital Dept of Gastroenterology | London, Greater London, United Kingdom, SE5 9RS John Radcliffe Hospital Dept of Gastroenterology | Oxford, Oxfordshire, United Kingdom, OX3 9DU Royal Hallamshire Hospital Dept of Gastroenterology | Sheffield, South Yorkshire, United Kingdom, S10 2JF Bradford Teaching Hospitals NHS Foundation Trust | Bradford, West Yorkshire, United Kingdom, BD9 6RJ The Ulster Hospital Department of Gastroenterology | Belfast, United Kingdom, BT16 1RH
Investigators

More Information

Additional Information

• To obtain more information on the study, click on this link

Additional Relevant MeSH Terms

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