Clinical trial NCT05353985: A Study of TAK-062 in Treatment of Active Celiac Disease in Participants Attempting a Gluten-Free Diet
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Celiac Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2022-04-29
Enrollment: 153
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score from Baseline to Week 12
timeFrame: Baseline (Week -1) to Week 12
Secondary outcomes:
measure: Change in Villous Height to Crypt Depth Ratio (Vh:Cd) from Baseline to Week 24
timeFrame: Baseline (Week -4, Run-in Period) to Week 24
measure: Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Adverse Events (SAEs) and Treatment-Related TEAEs
timeFrame: Up to Week 28
measure: Percentage of Participants with Positive Antidrug Antibodies (ADA) in Serum for TAK-062
timeFrame: Up to Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona, PC
state: Arizona
city: Paradise Valley
country: United States
facility: One of a Kind Clinical Research Center LLC
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic- Arizona
state: Arizona
city: Sun City
country: United States
facility: GI Alliance- Sun City
state: Arizona
city: Tucson
country: United States
facility: Adobe Clinical Research LLC
state: Arizona
city: Escondido
country: United States
facility: Gastroenterology and Liver Institute
state: California
city: Lancaster
country: United States
facility: Om Research LLC
state: California
city: Los Angeles
country: United States
facility: So. California Research Institute Med Group Inc./West Gastroenterology Med Group
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Mission Hills
country: United States
facility: Providence Facey Medical Foundation
state: California
city: Redwood City
country: United States
facility: Stanford University School of Medicine
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group, Inc.
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC
state: Colorado
city: Hamden
country: United States
facility: Medical Research Center of Connecticut, LLC 300143562
state: Connecticut
city: Plainville
country: United States
facility: Central Connecticut Endoscopy Center
state: Connecticut
city: Inverness
country: United States
facility: Nature Coast Clinical Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Wellness Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami Medical Center
state: Florida
city: Pensacola
country: United States
facility: Gastroenterology Associates of Pensacola, PA
state: Florida
city: Saint Augustine
country: United States
facility: St. Johns Center for Clinical Research
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research, LLC
state: Florida
city: Alpharetta
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Oakbrook Terrace
country: United States
facility: Lemah Creek Clinical Research
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University -GI
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical
state: Massachusetts
city: South Dartmouth
country: United States
facility: Hawthorn Medical Associates LLC
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Farmington Hills
country: United States
facility: Revive Research Institute, Inc
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Manhattan
country: United States
facility: Manhattan Clinical Research, LLC
state: New York
city: New York
country: United States
facility: New York University Medical Center PRIME
state: New York
city: New York
country: United States
facility: Blair S Lewis MD
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Charlotte
country: United States
facility: Tryon Medical Partners
state: North Carolina
city: Greenville
country: United States
facility: Carolina Digestive Diseases
state: North Carolina
city: Cincinnati
country: United States
facility: Gastro Health Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Gastroenterology and Hepatology
state: Ohio
city: Englewood
country: United States
facility: Dayton Gastroenterology, Inc
state: Ohio
city: Allentown
country: United States
facility: Eastern Pennsylvania Gastroeneterology and Liver Specialists
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Greenville
country: United States
facility: Gastroenterology Associates, PA
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center, LLC
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The Methodist Hospital 150520246
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: Houston
country: United States
facility: Spring Clinical Research
state: Texas
city: McAllen
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: Victoria
country: United States
facility: Victoria Gastroenterology
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Lynchburg
country: United States
facility: Blue Ridge Medical Research
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Seattle
country: United States
facility: Swedish Gastroenterology
state: Washington
city: Seattle
country: United States
facility: University of Washington Division of Gastroenterology
state: Washington
city: Spokane
country: United States
facility: Velocity Clinical Research
state: Washington
city: Brugge
country: Belgium
facility: AZ Sint-Lucas
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Sint-Niklaas
country: Belgium
facility: Vitaz
city: Edmonton
country: Canada
facility: Gastroenterology and Internal Medicine Research Institute (GIRI)
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface Hospital Inc. Section of Nephrology BG 007
state: Manitoba
city: Toronto
country: Canada
facility: Kensington Screening Clinic
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center McGill University
state: Quebec
city: Toulouse Cedex 09
country: France
facility: Hopital Rangueil Service de Gastro Enterologie et Nutrition
state: Haute Garonne
city: Neuilly
country: France
facility: Institut des MICI
state: Hauts De Seine
city: Saint Etienne
country: France
facility: CHU Saint Etienne - Hopital Nord Service de Gastro-Enterologie et Hepatologie
state: Loire
city: Lille cedex
country: France
facility: CHU Lille - Hopital Claude Huriez Service des maladies de I'appareil digestif
state: Nord
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou Gastro Enterologie et Oncologie Digestive
city: Cona
country: Italy
facility: Azienda Ospedaliero Universitaria di Ferrara
state: Ferrara
city: Milan
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
state: Milano
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti- Ospedale Pediatrico UOC Pediatria - G. Salesi
city: Como
country: Italy
facility: Ospedale Valduce 300205849
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Internal Medicine
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo Sezione di Medicina Interna
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana (Presidio di Cisanello) U.O. Gastroenterologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS UOC Medicina Interna e Gastroenterologia
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Torino
country: Italy
facility: Ospedale Umberto I di Torino S.C. Gastroenterologia
city: Krakow
country: Poland
facility: FutureMeds Krakow prev. Krakowskie Centrum Medyczne Sp. z o.o.
city: Nowy Targ
country: Poland
facility: ALLMEDICA sp. z o. o.
city: Rzeszow
country: Poland
facility: Gabinet Lekarski Bartosz Korczowski
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Warszawa
country: Poland
facility: Warsaw IBD Point Profesor Kierkus
city: Warszawa
country: Poland
facility: Komisja Bioetyczna przy Okregowej Izbie Lekarskiej w Warszawie
city: Wroclaw
country: Poland
facility: Melita Medical SP . Z O. O.
city: Zamosc
country: Poland
facility: ETG Zamosc
city: Barcelona
country: Spain
facility: Vall d'Hebron Research Institute
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal Servicio de Gastroenterologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria Digestive Service
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena Digestive Service
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet Servicio de Aparato Digestivo
city: London
country: United Kingdom
facility: Royal London Hospital Dept of Gastroenterology
state: Greater London
city: London
country: United Kingdom
facility: King's College Hospital Dept of Gastroenterology
state: Greater London
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital Dept of Gastroenterology
state: Oxfordshire
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital Dept of Gastroenterology
state: South Yorkshire
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospitals NHS Foundation Trust
state: West Yorkshire
city: Belfast
country: United Kingdom
facility: The Ulster Hospital Department of Gastroenterology
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: