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

Celiac Disease Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-101 for the Prevention of Gluten-Specific T Cell Activation in Subjects With Celiac Disease on a Gluten-Free Diet

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04530123
• Other study ID #: TAK-101-2001
• Secondary ID: U1111-1253-8169
• Status: Recruiting
• Phase: Phase 2
• Start date: June 23, 2022
• Est. completion date: October 30, 2025

Study information

• Verified date: May 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main aim of the study is to assess if TAK-101 can reduce gluten related symptoms and immune activation in adult participants with celiac disease (CeD) on a gluten-free diet (GFD).

Participants will receive TAK-101 and/or placebo through the vein on Day 1 and Day 8. All participants will receive active treatment at Week 24.

Description:

The drug being tested in this study is called TAK-101. TAK-101 is being tested to treat people who have celiac disease. The study has two cohorts planned. The first cohort has 1 dose level and the second cohort may include 1 or 2 dose levels, depending on safety, tolerability, and activity observed in the first cohort. Dosing in the second cohort will be based on data from the initial cohort.

The study will enrol approximately 108 patients (18 per arm). In the first cohort, approximately 45 participants will be randomly assigned in 1:2:2 ratio in one of the three arm groups which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). Eligible participants in Cohort 1 will receive:

• Group A: 2 infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.

• Group B: 1 infusion dose of 2 mg/kg of TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.

• Group C: 2 infusion doses of 2 mg/kg of TAK-101, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.

After the review of Cohort 1 safety data, a decision will be made to either stop the study or continue the study by the sponsor safety management team (SMT), based on recommendations from independent data monitoring committee (IDMC). If it is deemed appropriate to enroll both the TAK-101 4 mg/kg and 1 mg/kg dose level, approximately 63 participants may be randomly assigned in 1:2:2:2 ratio in Cohort 2 to receive:

• Group D: Two infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 2 mg/kg TAK-101 at Week 24.

• Group E: One infusion dose of 4 mg/kg TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 4 mg/kg TAK-101 at Week 24.

• Group F: Two infusion doses of 4mg/kg, 1 on Day 1 and 1 on day 8, followed by 1 infusion dose of 4 mg/kg TAK-101 at Week 24.

• Group G: TAK-101 1 mg/kg: Two infusion doses of 1 mg/kg TAK-101, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24 (1 mg/kg may not be needed based on review of Cohort 1 data).

In Cohort 2 if the 1 mg/kg treatment arm is not needed, Cohort 2 will consist of 45 participants in total, being randomized in a 1:2:2 ratio to 1 of the 3 treatment groups (Groups D, E, F) listed above.

If it is decided not to open the second cohort at the 4 mg/kg dose level and if 1 mg/kg dose is recommended to be tested by the IDMC, approximately 45 participants will be randomly assigned in 1:2:2 ratio to receive:

• Group D: Two infusion doses of placebo, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.

• Group E: One infusion dose of 1 mg/kg TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.

• Group F: Two infusion doses of 1 mg/kg, 1 on Day 1 and 1 on Day 8, followed by 1 infusion dose of 1 mg/kg TAK-101 at Week 24.

This trial will be conducted in United States and Canada. The overall time to participate in this study is approximately 24 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone OR plus a final visit after receiving their last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: October 30, 2025
• Est. primary completion date: October 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Biopsy-confirmed CeD that is well-controlled, defined as mild or with no ongoing signs 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 deamidated gliadin peptide (DGP) <3 × ULN.

Note: Participants may be retested for IgA tTG and IgG DGP to meet eligibility criteria at the discretion of the investigator. Intermittent symptoms would not exclude participants from participation as long as symptoms are generally well controlled in the opinion of the investigator, and as long as symptoms are back to baseline for 2 weeks before the run-in gluten challenge.

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

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

Exclusion Criteria:

1. Has received any investigational compound within 12 weeks (84 days) before signing of the informed consent or during the current study.

2. Has received TAK-101 (TIMP-GLIA) in a previous clinical study or as a therapeutic agent.

3. Has presence of inflammatory gastrointestinal disorders or autoimmune diseases, other than well-controlled autoimmune thyroid disease or well-controlled type 1 diabetes mellitus (defined as glycosylated hemoglobin <8% and no hospitalization in the last 12 months for hyper/hypoglycemia).

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

5. Has additional food allergies or intolerances that prevent participation in the food challenge.

6. Is receiving 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 chronic liver disease or positive for hepatitis B or C.

8. Has intolerable symptoms after the run-in gluten challenge and is unwilling to undergo subsequent posttreatment gluten challenges.

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Drug:
• Placebo
TAK-101 placebo-matching intravenous infusion
• TAK-101
TAK 101 intravenous infusion

Dietary Supplement:
• Gluten
Powder form (vital wheat gluten)

Locations

Country	Name	City	State
Australia	Bankstown-Lidcombe Hospital	Bankstown	New South Wales
Australia	Emeritus Research, Sydney	Botany	New South Wales
Australia	Northern Beaches Clinical Research	Brookvale	New South Wales
Australia	Emeritus Research, Melbourne	Camberwell	Victoria
Australia	St Vincent's Hospital Melbourne	Darlinghurst	New South Wales
Australia	Griffith University Clinical Trial Unit	Gold Coast	Queensland
Australia	Coastal Digestive Health	Maroochydore	Queensland
Australia	Sutherland Shire Clinical Research	Miranda	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Mater Hospital Brisbane	South Brisbane	Queensland
Australia	AusTrials Sunshine	St Albans	Victoria
Australia	AusTrials St Leonards	St Leonards	New South Wales
Australia	Wollongong Clinical Research	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	Scope Clinic	Brampton	Ontario
Canada	Gastroenterology and Internal Medicine Research Institute (GIRI)	Edmonton	Alberta
Canada	South Edmonton Gastroenterology	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	McMaster University	Hamilton	Ontario
Canada	Centricity Research London Victoria	London	Ontario
Canada	CHUM Centre de Recherche	Montreal	Quebec
Canada	CHUM Centre de Recherche	Montreal	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Centricity Research Ottawa Greenbelt	Nepean	Ontario
Canada	Scott Shulman Medicine Professional Corporation	North Bay	Ontario
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	The Ottawa Hospital - Riverside Campus	Ottawa	Ontario
Canada	Viable Clinical Research	Sudbury	Ontario
Canada	Kensington Screening Clinic	Toronto	Ontario
Canada	(G.I.R.I.) GI Research Institute	Vancouver	British Columbia
Canada	PerCuro Clinical Research Ltd.	Victoria	British Columbia
Canada	Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Canada	St. Boniface Hospital Inc.	Winnipeg	Manitoba
New Zealand	Optimal Clinical Trials - Central	Auckland
New Zealand	Optimal Clinical Trials - North	Auckland
New Zealand	Southern Clinical Trials Totara	Auckland
New Zealand	P3 Research Limited (Hawkes Bay)	Havelock North
New Zealand	Capital, Coast and Hutt Valley District Hutt Hospital	Lower Hutt
New Zealand	P3 Research Limited (Palmerston North)	Palmerston North
New Zealand	Lakeland Clinical Trials Wellington	Wellington
New Zealand	P3 Research Limited (Wellington)	Wellington
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Agile Clinical Research Trials	Atlanta	Georgia
United States	Amel Med LLC	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Specialists	Boston	Massachusetts
United States	Lahey Clinic Inc. - PARENT ACCOUNT	Burlington	Massachusetts
United States	MUSC Department of Gastroenterology	Charleston	South Carolina
United States	Javara Inc	Charlotte	North Carolina
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Precision Research Institute, LLC	Chula Vista	California
United States	Gastro Health Research	Cincinnati	Ohio
United States	Wellnow Urgent Care and Research	Cincinnati	Ohio
United States	Gastro Florida	Clearwater	Florida
United States	Cleveland Clinic - Gastroenterology and Hepatology	Cleveland	Ohio
United States	Asthma and Allergy Associates, PC	Colorado Springs	Colorado
United States	Advanced Gastroenterology Associates, PA.	Decatur	Texas
United States	Gastroenterology and Liver Institute	Escondido	California
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Gastroenterology Associates, PA	Greenville	South Carolina
United States	Penn State University Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Sweet Hope Research Specialty, Inc.	Hialeah	Florida
United States	Biopharma Informatic, LLC	Houston	Texas
United States	East Carolina Gastroenterology, PA	Jacksonville	North Carolina
United States	Biopharma Informatic, LLC	Katy	Texas
United States	Care Access Research Los Gatos	Los Gatos	California
United States	Wellness Clinical Research	Miami Lakes	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Gastroenterology Health Partners, PLLC	New Albany	Indiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	California Medical Research Associates Inc.	Northridge	California
United States	Lemah Creek Clinical Research	Oakbrook Terrace	Illinois
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	Berkshire Medical Center	Pittsfield	Massachusetts
United States	University Gastroenterology	Providence	Rhode Island
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Rockford Gastroenterology Associates, Ltd.	Rockford	Illinois
United States	One of a Kind Clinical Research Center LLC	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	GCP Clinical Research, LLC	Tampa	Florida
United States	GI Alliance - Webster	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Interferon-gamma Spot Forming Units (IFN-? SFUs) in Human Leukocyte Antigens Density Quotient (HLA-DQ2-positive) Participants Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay	IFN-? SFUs will be measured based on results of a gliadin-specific ELISpot assay using gluten-specific T cells which will be isolated from blood.	Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20)
Secondary	Percentage of Participants Experiencing at Least One Adverse Event (AE), Infusion Related Reaction (IRR), and Cytokine Release Syndrome (CRS)	An AE is defined as 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. An AE can therefore be any unfavorable and unintended sign (e.g., a markedly abnormal physical examination finding, vital sign value, laboratory test value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. IRR as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5 is defined as disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. CRS as per NCI CTCAE Version 5 is defined as a disorder characterized by nausea, headache, tachycardia, hypotension, rash, and shortness of breath caused by the release of cytokines from the cells.	From the first IV dose up to 30 days after last IV dose (Up to Week 28)
Secondary	Change From Baseline in Nausea Severity as Measured by the Celiac Disease Symptom Diary (CDSD) 3-day Average Score	The CDSD version 2.1 is an 8-item, self-administered questionnaire that evaluates the celiac disease (CeD) symptoms using 5-point Likert-type scales, where lower score indicating no symptoms and higher score indicating severe symptoms for all items except for frequency questions relating to stool counts, diarrhea, and vomiting frequency. The scores from the past 3 days with a 24-hour recall period will be averaged. For Weeks 8, 14, and 20, it is calculated as the average of the available daily scores recorded in the 3 days after the respective gluten challenge. The average score for Day 15 to 20 gluten challenge is the average of the daily scores from the initiation of gluten challenge to 3 days after the last gluten challenge.	Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20
Secondary	Change From Baseline in CDSD 3-day Peak Nausea Severity Score	The CDSD version 2.1 is an 8-item, self-administered questionnaire that evaluates the CeD symptoms using 5-point Likert-type scales, where lower score indicating no symptoms and higher score indicating severe symptoms for all items except for frequency questions relating to stool counts, diarrhea, and vomiting frequency. The scores from the past 3 days with a 24-hour recall period will be averaged. Peak score is the highest score in the 3 days following gluten challenge starting on the initiation of gluten challenge for challenges at Weeks 8, 14, and 20 and the highest score during and the 3 days following the Day 15-20 gluten challenge.	Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20
Secondary	Change From Baseline Before Gluten Challenge to 4 hours Post-gluten Challenge in Plasma Interleukin-2 (IL-2) on Day 15 and Weeks 8, 14, and 20	IL-2 levels in the plasma will be tested before and 4 hours after gluten challenge. IL-2 is acutely induced in participants with CeD and detected in the blood within 4 hours.	Baseline, Day 15, Weeks 8, 14, 20
Secondary	Plasma Concentration of TAK-101 After Each Dose		Predose and postdose at Weeks 0, 1 and 24
Secondary	Change From Baseline in Serum Concentration of Antidrug Antibody (ADAs) to TAK-101	ADA includes deamidated gliadin peptide- immunoglobulin G (DGP- IgG).	Predose at Weeks 0 and 1 and before gluten challenge at Weeks 2, 8, 14, 20, and 24

External Links

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