CompletedNCT04530123ClinicalTrials.gov record

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

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THE QUICK READ

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type: Interventional
Phase: Phase 2
Age range: 18 years - 75 years
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 102 Actual

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Read the full 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 12.5 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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.

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: Triple masked

Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE

Following a single-day 3 gram (g) oral run-in gluten challenge, participants will receive TAK-101 matching placebo intravenous (IV) infusion dose, once each 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. A third IV infusion dose of TAK-101 25 microgram per kilogram (µg/kg) GE will be given 23 weeks after the second dose at approximately Week 24.

Drug: Placebo · Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 25 µg/kg, IV infusion once on Day 1 followed by TAK-101 matching placebo 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. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24.

Drug: Placebo · Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 25 µg/kg GE IV infusion, once each 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. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24.

Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 matching placebo IV infusion, once each 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. A third IV infusion dose of TAK-101 25 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.

Drug: Placebo · Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 50 µg/kg GE IV infusion, once each 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. A third IV infusion dose of TAK-101 50 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.

Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 placebo-matching IV infusion, once each 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. A third IV infusion dose of TAK-101 12.5 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1. This group would be opened only if it is decided not to open Cohort 2 at the 50 µg/kg GE dose level.

Drug: Placebo · Drug: TAK-101 · Dietary Supplement: Gluten

Cohort 2, Group F: TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GE + TAK-101 12.5 µg/kg GE

Following a single-day 3 g oral run-in gluten challenge, participants will receive TAK-101 12.5 µg/kg GE IV infusion, once each 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. A third IV infusion dose of TAK-101 12.5 µg/kg GE will be given 23 weeks after the second dose at approximately Week 24. Cohort 2 would start based on the results of Cohort 1.

Drug: TAK-101 · Dietary Supplement: Gluten

Placebo DRUG

TAK-101 matching placebo intravenous infusion

TAK-101 DRUG

TAK 101 intravenous infusion

Gluten DIETARY_SUPPLEMENT

Powder form (vital wheat gluten)

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

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

Time frame: Baseline (Day 15), Week 3 (Day 20)

IFN-γ SFUs were measured based on results of a gliadin-specific ELISpot assay using peripheral blood mononuclear cells (PBMCs). Gliadin-specific cluster of differentiation 4 (CD4) T cells were a small percentage of the PBMCs and responded to gliadin peptide stimulation in vitro by producing the IFN-γ cytokine. Baseline was defined as Day 15.

Secondary measures

Percentage of Participants Experiencing at Least One Treatment-emergent Adverse Event (TEAE) and Adverse Events of Special Interest (AESIs)

Time frame: Up to Week 28

An adverse event (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 clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. A TEAE was defined as an AE that started, or severity worsened, or intensity increased after receiving the first study drug administration and up to within 30 days of last dose of study 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. AESIs are reported based on the Standardized MedDRA Queries (SMQs) and based on case report forms (CRFs).

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)

Time frame: Run-in (Visit 2 at Week -4), Weeks 8, 14, and 20

CDSD version 2.1 is a 8-item (severity of diarrhea, abdominal pain, bloating, nausea, and tiredness, frequency of bowel movement and vomiting, and a count of loosest stool forms), self-administered questionnaire that evaluates CeD symptoms using 5-point Likert-type scales (\[0\] none, \[1\] mild, \[2\] moderate, \[3\] severe, and \[4\] very severe), 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. Scores from past 3 days with a 24-hour recall period were averaged. For Run-in, Weeks 8, 14, and 20, each score was calculated as average of available daily scores recorded in 3 days prior and after the respective gluten challenge. Results are reported as least squares (LS) mean change from run-in at Weeks 8, 14 and 20, determined using a linear mixed-effect model for repeated measures (MMRM) analysis. A negative change from run-in indicates improvement.

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

Time frame: Run-in (Visit 2 at Week -4), Weeks 8, 14, and 20

CDSD version 2.1 is an 8-item (severity of diarrhea, abdominal pain, bloating, nausea, and tiredness, frequency of bowel movement and vomiting, and a count of loosest stool forms), self-administered questionnaire that evaluates CeD symptoms using 5-point Likert-type scales (\[0\] none, \[1\] mild, \[2\] moderate, \[3\] severe, and \[4\] very severe), 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. Scores from past 3 days with a 24-hour recall period were averaged. For Run-in, Weeks 8, 14, and 20, each score was calculated as average of the available daily scores recorded in the 3 days prior and after the respective gluten challenge. Results are reported as LS mean change from run-in at Weeks 8, 14 and 20, determined using a linear MMRM analysis. A negative change from run-in indicates improvement.

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

Time frame: Run-in (Visit 2 at Week -4), Weeks 8, 14, and 20

CDSD GI symptom severity score is an average of the daily GI symptom severity scores during the week. The daily GI symptom severity score is the average of the severity score for diarrhea, abdominal pain, bloating and nausea, ranging from 0 to 4. Symptom severity is evaluated using 5-point Likert-type scales (none, mild, moderate, severe, and very severe). Higher scores indicate more severe symptoms. Results are reported as LS mean change from run-in at Weeks 8, 14 and 20, determined using a linear MMRM analysis. A negative change from run-in indicates improvement.

Fold Change in Plasma Interleukin-2 (IL-2) From Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20

Time frame: Run-in (Visit 2 at Week -4), Week 2 (Day 15), and Weeks 8, 14, and 20

The pre-gluten to 4 hours post-gluten challenge log transformed fold change in plasma IL-2 from Run-in (Visit 2) to Day 15, and Weeks 8, 14, and 20 were compared. Results are reported as LS mean change from run-in at Day 15, Weeks 8, 14 and 20, determined using a linear MMRM analysis.

Fold Change in Plasma IL-2 at Specified Time Points

Time frame: Run-in (Visit 2 at Week -4), Week 2 (Day 15), and Weeks 8, 14, and 20

The pre-gluten to 4 hours post-gluten challenge log-transformed fold change in plasma IL-2 at each of the time points is reported.

Plasma Concentration of TAK-101 After Each Dose

Time frame: At end of infusion of Weeks 0, 1 and 24

Free gliadin concentration in the plasma was measured and reported.

Serum Concentration of Antidrug Antibody (ADAs) to Various Doses of TAK-101

Time frame: Predose at Weeks 1 and 24; and before gluten challenge at Weeks 2, 14, and 20

ADA includes deamidated gliadin peptide- immunoglobulin G (DGP- IgG). Serum Concentration of ADAs was measured in Enzyme-Linked ImmunoAssay Units per milliliter denoted as EliA U/mL.

Results are posted in the registry.

Review the complete result tables and limitations in the official record.

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Research locations (48)

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Find a location in this study

48 locations

One of a Kind Clinical Research Center LLCScottsdale, Arizona, United StatesStatus unknown

What this study involves

About the research

Who may be able to participate?

Treatment, groups and participation

What researchers are measuring

Primary measures

Secondary measures

Research locations (48)

Study team and timeline

Official study contacts

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