Clinical trial NCT04530123: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Celiac Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-08-28
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 2 cohorts planned. Cohort 1 has 1 dose level and the Cohort 2 may include 1 or 2 additional dose levels, depending on safety, tolerability, and activity observed in Cohort 1. Dosing in the Cohort 2 will be based on data from Cohort 1.

The study will enroll approximately 90 patients. In Cohort 1, 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 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 micrograms per kilogram (µg/kg) Gluten Epitopes (GE) TAK-101 at Week 24.
* Group B: 1 infusion dose of 25 µg/kg GE TAK-101 on Day 1 followed by 1 infusion dose of placebo on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.
* Group C: 2 infusion doses of 25 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.

If it is deemed appropriate to enroll both the TAK-101 50 µg/kg GE and the 12.5 µg/kg GE dose levels in Cohort 2, approximately 45 participants may be randomly assigned in 1:2:2 ratio in Cohort 2 to receive:

* Group A: Two infusion doses of placebo, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 25 µg/kg GE TAK-101 at Week 24.
* Group D: Two infusion doses of 50 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 50 µg/kg GE TAK-101 at Week 24.
* Group F: Two infusion doses of 12.5 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg GE TAK-101 at Week 24.

If it is decided not to open the second cohort at the 50 µg/kg GE dose level and if 1 2.5 µg/kg GE dose is recommended to be tested by the independent data monitoring committee (IDMC), approximately 27 participants will be randomly assigned in 1:2 ratio to receive:

* Group E: Two infusion doses of placebo, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg GE TAK-101 at Week 24.
* Group F: Two infusion doses of 12.5 µg/kg GE TAK-101, 1 infusion dose on Day 1 and 1 infusion dose on Day 8, followed by 1 infusion dose of 12.5 µg/kg TAK-101 at Week 24.

This trial will be conducted globally. The overall time to participate in this study is approximately 34 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.

Eligibility criteria: 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 able to maintain a gluten-free diet (GFD) for ≥6 months.
3. Must be HLA-DQ2.5 and/or HLA-DQ8 positive during screening laboratory testing.

Exclusion Criteria:

1. Has received any investigational compound within 12 weeks (84 days) or 5 half-lives, whichever is longer, before signing of the informed consent form (ICF).
2. Has received TAK-101 in a previous clinical study.
3. Has presence of other inflammatory gastrointestinal (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 medications.

   * Examples of conditions that are exclusionary include: inflammatory bowel disease, eosinophilic gastroenteritis or colitis, and microscopic colitis requiring treatment in the 6 months before screening.
   * Examples of conditions that may be permissible after discussion with the medical monitor/or sponsor include: systemic autoimmune disease such as scleroderma, psoriatic or rheumatoid arthritis, lupus that is stable and without GI involvement, well controlled autoimmune thyroid disease, well controlled type 1 diabetes or proton pump inhibitor -responsive eosinophilic esophagitis in symptomatic and histologically confirmed remission.
4. Has known or suspected refractory CeD or ulcerative jejunitis.
5. Has known or suspected allergy to wheat, such as hypersensitivity and/or anaphylaxis including wheat-dependent-exercise induced anaphylaxis (WDEIA). If there is a possible history of urticaria, angioedema, or anaphylaxis to wheat, investigators should perform testing for wheat anti-Immunoglobulin (anti-IgE) antibodies or refer to an allergist for evaluation prior to enrollment to rule out any of these allergies.
6. 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 clinically significant liver disease or positive test result for hepatitis B or C.
8. Has intolerable symptoms after the run-in gluten challenge and is unwilling to undergo subsequent post treatment gluten challenges.
9. Has known allergy to or intolerance of TAK-101 or any of its ingredients or excipients. Also, any subject with a symptomatic allergic reaction that is confirmed by laboratory serology such as elevated tryptase levels following the administration of TAK-101 will be excluded from future dosing.
10. Has a current diagnosis of active malignancy or malignancy diagnosed in the 5 years prior to screening or is receiving ongoing treatment for malignancy.

Primary outcomes:
measure: Change From Baseline in Interferon-gamma Spot Forming Units (IFN-γ SFUs) in Human Leukocyte Antigens Density Quotient (HLA-DQ2.5-positive) Participants Based on Results of a Gliadin-Specific Enzyme-Linked Immunospot (ELISpot) Assay
timeFrame: Baseline (Day 15, or Day 1 in the absence of Day 15) to Week 3 (Day 20)
Secondary outcomes:
measure: Percentage of Participants Experiencing at Least One Adverse Event (AE) and Adverse Events of Special Interest (AESIs)
timeFrame: From the first IV dose up to 30 days after last IV dose (Up to Week 28)
measure: Change From Run-in (Visit 2) to Weeks 8, 14, and 20 in the Pre- to Post-gluten Challenge Change of the 3-day Average Nausea Severity Score as Measured in Celiac Disease Symptom Diary (CDSD)
timeFrame: Run-in (Visit 2), Weeks 8, 14, and 20
measure: Change From Run-in (Visit 2) to Weeks 8,14, and 20 in the Pre- to Post-gluten Challenge Change in CDSD 3-day Peak Nausea Severity Score
timeFrame: Run-in (Visit 2), Weeks 8, 14, and 20
measure: Change From Run-in (Visit 2) to Weeks 8, 14, and 20 in the Pre- to Post-gluten Challenge Change in Weekly Gastrointestinal (GI) Symptom Severity Score
timeFrame: Run-in (Visit 2), Weeks 8, 14, and 20
measure: Fold Change in Plasma Interleukin-2 (IL-2) from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20
timeFrame: Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20
measure: Fold Change in Plasma IL-2 at Specified Time Points
timeFrame: Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20
measure: Plasma Concentration of TAK-101 After Each Dose
timeFrame: Predose and postdose at Weeks 0, 1 and 24
measure: Serum Concentration of Antidrug Antibody (ADAs) to Various Doses of TAK-101
timeFrame: Predose at Week 1 and before gluten challenge at Weeks 2, 14, 20, and 24
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: One of a Kind Clinical Research Center LLC
state: Arizona
city: Escondido
country: United States
facility: Gastroenterology and Liver Institute
state: California
city: Poway
country: United States
facility: Cadena Care Institute, Inc.
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, PC
state: Colorado
city: Tampa
country: United States
facility: GCP Clinical Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Burr Ridge
country: United States
facility: Lemah Creek Clinical Research
state: Illinois
city: Rockford
country: United States
facility: Gastroenterology Associates, PA
state: Illinois
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates, Ltd.
state: Illinois
city: New Albany
country: United States
facility: Berkshire Medical Center
state: Indiana
city: New Albany
country: United States
facility: Gastroenterology Health Partners, PLLC
state: Indiana
city: Boston
country: United States
facility: Boston Specialists
state: Massachusetts
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: Pittsfield
country: United States
facility: Berkshire Medical Center, Inc.
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Chesterfield
country: United States
facility: Wellness Clinical Research
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Inwood
country: United States
facility: Basil Clinical
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center. New York Presbyterian Hospital
state: New York
city: Jacksonville
country: United States
facility: East Carolina Gastroenterology, PA
state: North Carolina
city: Providence
country: United States
facility: GI Alliance-Rhode Island
state: Rhode Island
city: Georgetown
country: United States
facility: Amel Med LLC
state: Texas
city: Ogden
country: United States
facility: Care Access Research - Salt Lake City
state: Utah
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: AU
city: Botany
country: Australia
facility: Emeritus Research, Sydney
state: NS
city: North Mackay
country: Australia
facility: Coral Sea Clinical Research Institute
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Camberwell
country: Australia
facility: Emeritus Research, Melbourne
state: Victoria
city: Epping
country: Australia
facility: The Northern Hospital
state: Victoria
city: Midland
country: Australia
facility: St John of God Midland
state: Western Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
city: Edmonton
country: Canada
facility: Gastroenterology and Internal Medicine Research Institute (GIRI)
state: Alberta
city: Victoria
country: Canada
facility: PerCuro Clinical Research Ltd.
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: North bay
country: Canada
facility: Scott Shulman Medicine Professional Corporation
state: Ontario
city: Quebec
country: Canada
facility: DIEX Recherche Quebec Inc.
city: Silverdale
country: New Zealand
facility: Silverdale Medical
state: Auckland
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials - North
state: AU
city: New Lynn
country: New Zealand
facility: Southern Clinical Trials Totara
state: AU
city: Dunedin
country: New Zealand
facility: Momentum Clinical Research Dunedin
state: OT
city: Wellington
country: New Zealand
facility: P3 Research Limited (Wellington)
state: OT
city: Boulcott
country: New Zealand
facility: Capital, Coast and Hutt Valley - Wellington Regional Hospital
state: WG
city: Upper Hutt
country: New Zealand
facility: Lakeland Clinical Trials Wellington
state: WG
city: Grafton
country: New Zealand
facility: Optimal Clinical Trials - Central
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: