A Study of TAK-062 in Treatment of Active Celiac Disease in Participants Attempting a Gluten-Free Diet

Celiac Disease Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05353985
• Other study ID #: TAK-062-2001
• Secondary ID: 2020-005438-14
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: May 6, 2025

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim is to see how TAK-062 works to reduce celiac-related symptoms and improve small intestinal damage due to gluten exposure, in participants with celiac disease (CeD) attempting to maintain a gluten-free diet (GFD) in treated participants versus placebo controls.

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:

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

2. 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.

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

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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 357
• Est. completion date: May 6, 2025
• Est. primary completion date: May 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 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.

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 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.

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.

18. 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:

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.

Related Conditions & MeSH terms

• Celiac Disease

Intervention

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.

Locations

Country	Name	City	State
Belgium	AZ Sint-Lucas	Brugge
Belgium	AZ Maria Middelares	Gent
Belgium	Vitaz	Sint-Niklaas
Canada	Gastroenterology and Internal Medicine Research Institute (GIRI)	Edmonton	Alberta
Canada	McGill University Health Center McGill University	Montreal	Quebec
Canada	Kensington Screening Clinic	Toronto	Ontario
Canada	St. Boniface Hospital Inc. Section of Nephrology BG 007	Winnipeg	Manitoba
France	CHU Lille - Hopital Claude Huriez Service des maladies de I'appareil digestif	Lille cedex	Nord
France	Institut des MICI	Neuilly	Hauts De Seine
France	Hopital Europeen Georges Pompidou Gastro Enterologie et Oncologie Digestive	Paris
France	CHU Saint Etienne - Hopital Nord Service de Gastro-Enterologie et Hepatologie	Saint Etienne	Loire
France	Hopital Rangueil Service de Gastro Enterologie et Nutrition	Toulouse Cedex 09	Haute Garonne
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti- Ospedale Pediatrico UOC Pediatria - G. Salesi	Ancona
Italy	Ospedale Valduce 300205849	Como
Italy	Azienda Ospedaliero Universitaria di Ferrara	Cona	Ferrara
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milan	Milano
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Internal Medicine	Palermo
Italy	Fondazione IRCCS Policlinico San Matteo Sezione di Medicina Interna	Pavia
Italy	Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello) U.O. Gastroenterologia	Pisa
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS UOC Medicina Interna e Gastroenterologia	Roma
Italy	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona	Salerno
Italy	Ospedale Umberto I di Torino S.C. Gastroenterologia	Torino
Poland	FutureMeds Krakow prev. Krakowskie Centrum Medyczne Sp. z o.o.	Krakow
Poland	ALLMEDICA sp. z o. o.	Nowy Targ
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Gabinet Lekarski Bartosz Korczowski	Rzeszow
Poland	Komisja Bioetyczna przy Okregowej Izbie Lekarskiej w Warszawie	Warszawa
Poland	Warsaw IBD Point Profesor Kierkus	Warszawa
Poland	Melita Medical SP . Z O. O.	Wroclaw
Poland	ETG Zamosc	Zamosc
Spain	Vall d'Hebron Research Institute	Barcelona
Spain	Hospital Universitario Ramon y Cajal Servicio de Gastroenterologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria Digestive Service	Malaga
Spain	Hospital Universitario Virgen Macarena Digestive Service	Sevilla
Spain	Hospital Universitario Miguel Servet Servicio de Aparato Digestivo	Zaragoza
United Kingdom	The Ulster Hospital Department of Gastroenterology	Belfast
United Kingdom	Bradford Teaching Hospitals NHS Foundation Trust	Bradford	West Yorkshire
United Kingdom	King's College Hospital Dept of Gastroenterology	London	Greater London
United Kingdom	Royal London Hospital Dept of Gastroenterology	London	Greater London
United Kingdom	John Radcliffe Hospital Dept of Gastroenterology	Oxford	Oxfordshire
United Kingdom	Royal Hallamshire Hospital Dept of Gastroenterology	Sheffield	South Yorkshire
United States	Eastern Pennsylvania Gastroeneterology and Liver Specialists	Allentown	Pennsylvania
United States	Agile Clinical Research Trials	Alpharetta	Georgia
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Lahey Hospital and Medical	Burlington	Massachusetts
United States	Tryon Medical Partners	Charlotte	North Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Gastro Health Research	Cincinnati	Ohio
United States	Cleveland Clinic - Gastroenterology and Hepatology	Cleveland	Ohio
United States	Asthma and Allergy Associates, PC	Colorado Springs	Colorado
United States	Dayton Gastroenterology, Inc	Englewood	Ohio
United States	Gastroenterology and Liver Institute	Escondido	California
United States	Revive Research Institute, Inc	Farmington Hills	Michigan
United States	Carolina Digestive Diseases	Greenville	North Carolina
United States	Gastroenterology Associates, PA	Greenville	South Carolina
United States	Medical Research Center of Connecticut, LLC 300143562	Hamden	Connecticut
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Spring Clinical Research	Houston	Texas
United States	The Methodist Hospital 150520246	Houston	Texas
United States	Indiana University -GI	Indianapolis	Indiana
United States	Nature Coast Clinical Research, LLC	Inverness	Florida
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	Om Research LLC	Lancaster	California
United States	Research Solutions of Arizona, PC	Litchfield Park	Arizona
United States	So. California Research Institute Med Group Inc./West Gastroenterology Med Group	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Manhattan Clinical Research, LLC	Manhattan	New York
United States	Biopharma Informatic, LLC	McAllen	Texas
United States	University of Miami Medical Center	Miami	Florida
United States	Wellness Clinical Research	Miami Lakes	Florida
United States	Providence Facey Medical Foundation	Mission Hills	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Blair S Lewis MD	New York	New York
United States	New York University Medical Center PRIME	New York	New York
United States	Lemah Creek Clinical Research	Oakbrook Terrace	Illinois
United States	One of a Kind Clinical Research Center LLC	Paradise Valley	Arizona
United States	Gastroenterology Associates of Pensacola, PA	Pensacola	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Central Connecticut Endoscopy Center	Plainville	Connecticut
United States	Rapid City Medical Center, LLC	Rapid City	South Dakota
United States	Stanford University School of Medicine	Redwood City	California
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Rochester Clinical Research	Rochester	New York
United States	St. Johns Center for Clinical Research	Saint Augustine	Florida
United States	Washington University, School of Medicine	Saint Louis	Missouri
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Mayo Clinic- Arizona	Scottsdale	Arizona
United States	Swedish Gastroenterology	Seattle	Washington
United States	University of Washington Division of Gastroenterology	Seattle	Washington
United States	Hawthorn Medical Associates LLC	South Dartmouth	Massachusetts
United States	Velocity Clinical Research	Spokane	Washington
United States	GI Alliance- Sun City	Sun City	Arizona
United States	GCP Clinical Research, LLC	Tampa	Florida
United States	Adobe Clinical Research LLC	Tucson	Arizona
United States	Victoria Gastroenterology	Victoria	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score from Baseline 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.	Baseline (Week -1) to Week 12
Secondary	Change in Villous Height to Crypt Depth Ratio (Vh:Cd) from Baseline 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.	Baseline (Week -4, Run-in Period) to Week 24
Secondary	Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Adverse Events (SAEs) and Treatment-Related TEAEs	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.	Up to Week 28
Secondary	Percentage of Participants with Positive Antidrug Antibodies (ADA) in Serum for TAK-062	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.	Up to Week 28

External Links

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