Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04530123
Recruitment Status : Not yet recruiting
First Posted : August 28, 2020
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of the study is to compare the number of baseline IFN-γ SFUs to the number of IFN-γ SFUs after a 6-day oral gluten challenge among participants treated with TAK-101 versus placebo.

Condition or disease Intervention/treatment Phase
Celiac Disease Drug: Placebo Drug: TAK-101 Dietary Supplement: Gluten Phase 2

Detailed 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.

The study will enroll approximately 108 patients. 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 will receive: Cohort 1:

  • Placebo: 2 infusions
  • TAK-101 2 mg/kg: 1 infusion + placebo: 1 infusion
  • TAK-101 2 mg/kg: 2 infusions

All participants will be asked to take TAK-101 intravenous (IV) infusion and TAK-101 placebo matching infusion on Days 1 and 8. After completion of Cohort 1, Cohort 2 may start based on the review of Cohort 1 data by an external data monitoring committee (DMC). Approximately 86 participants may be randomly assigned in 1:2:2:2 ratio in Cohort 2 to receive: Cohort 2 (1 mg/kg may not be needed based on review of Cohort 1 data):

  • Placebo: 2 infusions
  • TAK-101 4 mg/kg : 1 infusion + placebo: 1 infusion
  • TAK-101 4 mg/kg: 2 infusions
  • TAK-101 1 mg/kg: 2 infusions

The TAK-101 1 mg/kg, 2 infusions may be open based on an interim analysis of the cohort 1 Interferon-gamma Spot Forming Units (IFN-γ SFUs) reviewed by the DMC. If TAK-101 1 mg/kg, 2 infusions is not open, approximately 86 participants will be randomly assigned in 1:2:2 ratio to receive:

  • Placebo: 2 infusions
  • TAK-101 1 mg/kg: 1 infusion + placebo: 1 infusion
  • TAK-101 1 mg/kg: 2 infusions

This trial will be conducted in United States and Canada. The overall time to participate in this study is approximately 26 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Estimated Study Start Date : August 29, 2021
Estimated Primary Completion Date : December 2, 2022
Estimated Study Completion Date : March 24, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Placebo Comparator: Cohort 1: Placebo (2 Infusions)
Following a single-day 3 gram (g) oral run-in gluten challenge, participants will receive TAK-101 placebo-matching intravenous (IV) infusion, once on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20.
Drug: Placebo
TAK-101 placebo-matching intravenous infusion

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Experimental: Cohort 1: TAK-101 2 mg/kg (1 Infusion) + Placebo (1 Infusion)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 2 mg/kg, IV infusion once on Day 1 followed by TAK-101 placebo-matching IV infusion, once on Day 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20.
Drug: TAK-101
TAK 101 intravenous infusion
Other Name: TIMP-GLIA

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Experimental: Cohort 1: TAK-101 2 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 2 mg/kg IV infusion, once on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20.
Drug: TAK-101
TAK 101 intravenous infusion
Other Name: TIMP-GLIA

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Placebo Comparator: Cohort 2: Placebo (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 placebo-matching IV infusion, once on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. Cohort 2 would start based on the results of Cohort 1.
Drug: Placebo
TAK-101 placebo-matching intravenous infusion

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Experimental: Cohort 2:TAK-101 4 mg/kg (1 Infusion)+placebo (1 Infusion)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 4 mg/kg, IV infusion once on Day 1 followed by TAK-101 placebo-matching IV infusion, once on Day 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Name: TIMP-GLIA

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Experimental: Cohort 2: TAK-101 4 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 4 mg/kg IV infusion, once on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Name: TIMP-GLIA

Dietary Supplement: Gluten
Powder form (vital wheat gluten)

Experimental: Cohort 2: TAK-101 1 mg/kg (2 Infusions)
Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 1 mg/kg IV infusion, once on Days 1 and 8, followed by 12 g/day gluten for 3 days followed by 6 g/day gluten for 3 days starting at Week 2. Participants will then undergo single-day 3 g gluten challenges at Weeks 8, 14, and 20. Cohort 2 would start based on the results of Cohort 1.
Drug: TAK-101
TAK 101 intravenous infusion
Other Name: TIMP-GLIA

Dietary Supplement: Gluten
Powder form (vital wheat gluten)




Primary Outcome Measures :
  1. Change From Baseline in Interferon-gamma Spot Forming Units (IFN-γ SFUs) Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay [ Time Frame: Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20) ]
    IFN-γ SFUs will be measured based on results of a gliadin-specific ELISpot assay using gluten-specific T cells which will be isolated from blood.


Secondary Outcome Measures :
  1. Number of Participants with at Least one Adverse Event (AE) [ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]
    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.

  2. Number of Participants with Infusion Reaction (IR) [ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]
  3. Number of Participants with Cytokine Release Syndrome (CRS) [ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]
  4. Number of Participants with Markedly Abnormal Vital Sign Values [ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]
    Vital signs will include assessment of body temperature, respiratory rate, blood pressure and pulse.

  5. Number of Participants with Markedly Abnormal Laboratory Test Values [ Time Frame: From the first injection up to 30 days after last injection (Up to Week 24) ]
    Clinical laboratory values will include test for hematology, serum chemistry and urinalysis including liver tests.

  6. Change From Baseline in Celiac Disease Symptom Diary (CDSD) 3-day Average Score [ Time Frame: Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20 ]
    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.

  7. Change From Baseline in CDSD 3-day Peak Score [ Time Frame: Baseline and Day 1 post gluten challenge on Day 20 (Week 3) and Weeks 8, 14 and 20 ]
    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.

  8. Change From Baseline Pre- to 4 hours Post-gluten Challenge in Plasma Interleukin-2 (IL-2) [ Time Frame: Baseline to Week 20 ]
  9. Plasma Concentration of TAK-101 After the First and Second Dose [ Time Frame: Predose and postdose at Weeks 0 and 1 ]
  10. Change From Baseline in Serum Concentration of Antidrug Antibody (ADAs) to TAK-101 [ Time Frame: Predose and postdose at Weeks 0 and 1 and before gluten challenge at Week 2, 8, 14 and 20 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Biopsy-confirmed celiac disease (CeD) that is well-controlled, defined as mild or with no ongoing signs or symptoms felt to be related to active CeD and with IgA tTG <2 × upper limit of normal (ULN) and IgG DGP <3 × ULN.

    Note: Participants may be retested for IgA tissue transglutaminase (tTG) and IgG deamidated gliadin peptide (DGP) to meet eligibility criteria at the discretion of the investigator.

  2. Must be on 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530123


Contacts
Layout table for location contacts
Contact: Takeda Study Registration Call Center +1-877-825-3327 medinfoUS@takeda.com

Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Director: Medical Director Clinical Science Takeda
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04530123    
Other Study ID Numbers: TAK-101-2001
U1111-1253-8169 ( Registry Identifier: World Health Organization )
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases