Celiac Disease
Conditions
Keywords
Drug Therapy
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.
Interventions
DRUGPlacebo
TAK-101 placebo-matching intravenous infusion
DRUGTAK-101
TAK 101 intravenous infusion
DIETARY_SUPPLEMENTGluten
Powder form (vital wheat gluten)
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing at Least One Adverse Event (AE) and Adverse Events of Special Interest (AESIs) | From the first IV dose up to 30 days after last IV dose (Up to Week 28) | 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. An AESI (serious or nonserious) is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate. |
| 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) | Run-in (Visit 2), Weeks 8, 14, and 20 | 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 prior and after the respective gluten challenge. |
| 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 | Run-in (Visit 2), 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. Peak score is the highest score in the 3 days prior and following gluten challenge at Weeks 8, 14, and 20. |
| 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 | Run-in (Visit 2), 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. GI symptom severity score ranges from 0 to 20 with higher score indicating more severe disease. |
| Fold Change in Plasma Interleukin-2 (IL-2) from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20 | Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20 | The pre-/post-gluten challenge fold change in plasma IL-2 from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20 will be compared. |
| Fold Change in Plasma IL-2 at Specified Time Points | Pre-/post-gluten challenge at Run-in (Visit 2), Day 15, and Weeks 8, 14, and 20 | The pre-/post-gluten challenge fold change in plasma IL-2 at each of the time points will be compared. |
| Plasma Concentration of TAK-101 After Each Dose | Predose and postdose at Weeks 0, 1 and 24 | — |
| Serum Concentration of Antidrug Antibody (ADAs) to Various Doses of TAK-101 | Predose at Week 1 and before gluten challenge at Weeks 2, 14, 20, and 24 | ADA includes deamidated gliadin peptide- immunoglobulin G (DGP- IgG). |
Countries
Australia, Canada, New Zealand, United States
Contacts
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed