TAK-101 for Celiac Disease

Not currently recruiting at 117 trial locations

Overseen By Stephanie Moleski

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Inflammatory bowel disease, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if TAK-101 can reduce symptoms and immune reactions in individuals with celiac disease who follow a gluten-free diet but still experience gluten-related issues. Participants will receive either TAK-101 or a placebo at different stages, with all eventually receiving the active treatment. This trial may suit adults with biopsy-confirmed celiac disease who maintain a gluten-free diet and have mild or no ongoing symptoms. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressants or corticosteroids, you may need to stop them, as ongoing treatment with these is not allowed.

Is there any evidence suggesting that TAK-101 is likely to be safe for humans?

Research has shown that TAK-101 was well tolerated in earlier trials. These studies found that it stopped the immune reaction caused by gluten in people with celiac disease, meaning it did not trigger a harmful response from the body's defense system. No serious side effects were reported in these studies. This is encouraging for prospective trial participants, as TAK-101 appears safe based on past research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for celiac disease?

TAK-101 is unique because it offers a novel approach to managing celiac disease by potentially modifying the immune response to gluten. Unlike the current standard of care, which primarily involves strict adherence to a gluten-free diet, TAK-101 uses a specific infusion method designed to help the body better tolerate gluten exposure. Researchers are excited about TAK-101 because it could significantly improve the quality of life for people with celiac disease by reducing the burden of dietary restrictions and minimizing accidental gluten exposure reactions.

What evidence suggests that TAK-101 might be an effective treatment for celiac disease?

Research has shown that TAK-101 can help people with celiac disease who accidentally consume gluten by reducing their immune response. In this trial, participants in various treatment arms will receive different dosages of TAK-101 or a placebo. TAK-101 significantly decreased the body's reaction to gluten compared to a placebo. It also prevented the immune system from reacting to gluten, suggesting it may help the body handle gluten better. These findings indicate that TAK-101 could be a promising treatment for managing celiac disease symptoms for those following a gluten-free diet. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults with celiac disease who have been on a gluten-free diet for at least 6 months can join. They must test positive for HLA-DQ2 or HLA-DQ8 and have mild or no symptoms of active celiac disease, with certain antibody levels below specified limits. People can't join if they've had certain treatments recently, have refractory celiac disease, other serious health conditions, or can't tolerate gluten challenges.

Inclusion Criteria

My celiac disease is under control with specific blood test levels within the normal range.

I tested positive for HLA-DQ2 or HLA-DQ8.

You can still join the study if you have occasional symptoms, as long as they are well managed and have returned to normal for at least 2 weeks before the gluten challenge.

Exclusion Criteria

I am currently on or have recently taken immunosuppressants or steroids.

I have chronic liver disease or hepatitis B/C.

I have celiac disease that doesn't respond to a gluten-free diet or I have ulcerative jejunitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-101 or placebo infusions on Day 1 and Day 8, followed by gluten challenges and a final infusion at Week 24

24 weeks

Multiple visits including Day 1, Day 8, and Week 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Final visit after last dose

What Are the Treatments Tested in This Trial?

Interventions

• TAK-101

Trial Overview The trial is testing TAK-101's ability to prevent immune reactions and symptoms when people with celiac disease eat gluten. Participants will get TAK-101 or a placebo through an IV on two separate days and everyone gets the real treatment after six months.

How Is the Trial Designed?

Group I: 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 Experimental Treatment 2 Interventions

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.

Group II: Cohort 2, Group E: Placebo + Placebo + TAK-101 12.5 µg/kg GE Experimental Treatment 3 Interventions

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.

Group III: Cohort 2, Group D: TAK-101 50 µg/kg GE + TAK-101 50 µg/kg GE+ TAK-101 50 µg/kg GE Experimental Treatment 2 Interventions

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.

Group IV: Cohort 2, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE Experimental Treatment 3 Interventions

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 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.

Group V: Cohort 1, Group C: TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE + TAK-101 25 µg/kg GE Experimental Treatment 2 Interventions

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.

Group VI: Cohort 1, Group B: TAK-101 25 µg/kg GE + Placebo + TAK-101 25 µg/kg GE Experimental Treatment 3 Interventions

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 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. 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.

Group VII: Cohort 1, Group A: Placebo + Placebo + TAK-101 25 µg/kg GE Experimental Treatment 3 Interventions

Following a single-day 3 gram (g) oral run-in gluten challenge, participants will receive TAK-101 placebo-matching 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.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

The study identified a significant relationship between the presence of TCRγδ+ T cells and the absence of IL4-producing T cells in the intestinal mucosa of children with overt celiac disease (CD), suggesting these cells play a crucial role in the progression from potential-CD to overt-CD.

The changes in these T cell populations correlate with the severity of intestinal mucosal lesions, indicating that monitoring TCRγδ+ and IL4+ T cells could serve as potential biomarkers for disease progression and targets for new treatments in celiac disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal Cellular Biomarkers of Mucosal Lesion Progression in Pediatric Celiac Disease. Vitale, S., Maglio, M., Picascia, S., et al.[2021]

In a study of 103 pediatric patients with celiac disease on a gluten-free diet, 19% showed persistent enteropathy after at least 12 months, indicating that some children do not fully recover despite dietary adherence.

The immunoglobulin A tissue transglutaminase (tTG) levels were not reliable indicators of mucosal recovery, as 43% of patients with persistent enteropathy had elevated tTG, suggesting a need to reevaluate monitoring and management strategies for celiac disease in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of IgA tTG in Predicting Mucosal Recovery in Children With Celiac Disease on a Gluten-Free Diet. Leonard, MM., Weir, DC., DeGroote, M., et al.[2021]

A point-of-care test (POCT) based on IgA/IgG-deamidated gliadin peptide showed a sensitivity of 67.1% in detecting persistent villous atrophy (VA) in celiac disease, which is higher than other surrogate markers like tissue transglutaminase (TTG) and endomysial antibodies (EMA).

The POCT could offer a non-invasive and immediate assessment of mucosal healing during follow-up consultations, potentially improving patient management in celiac disease without the need for invasive duodenal biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of an IgA/IgG-Deamidated Gliadin Peptide Point-of-Care Test in Predicting Persistent Villous Atrophy in Patients With Celiac Disease on a Gluten-Free Diet. Lau, MS., Mooney, PD., White, WL., et al.[2018]

In a study of 220 infants at genetic risk for celiac disease (CeD), early production of anti-native gliadin antibodies (AGA-IgA) was identified as a potential marker for tolerance, as 15.3% of healthy controls produced these antibodies without developing celiac disease.

The research also found that changes in gene expression and serum cytokine levels occurred before the appearance of more specific antibodies (anti-tTG), indicating that these immunological events may precede the development of villous atrophy in CeD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody Profile, Gene Expression and Serum Cytokines in At-Risk Infants before the Onset of Celiac Disease. Auricchio, R., Galatola, M., Cielo, D., et al.[2023]

Celiac disease affects about 1% of the U.S. population, with higher prevalence in individuals with a family history, highlighting the importance of genetic predisposition in its diagnosis and management.

Comprehensive nutritional management and proper diagnostic strategies, including serologic testing and HLA haplotypes, are crucial for effective treatment and monitoring of celiac disease, especially given its association with various other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies. McAllister, BP., Williams, E., Clarke, K.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9053078/

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in ... Phase 2a study: TAK-101 efficacy outcomes. In the placebo group, ex ... Longer-term effects of TAK-101 on celiac disease symptoms were not fully evaluated.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04530123

Dose-Ranging Study of the Efficacy and Safety of TAK-101 ... 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) ...

3. journal.ppcr.org journal.ppcr.org/index.php/ppcrjournal/article/view/185

A randomized, double-blind, placebo-controlled, Phase 1/2a ... This is a first Phase 1/2a placebo control randomized trial to assess the safety and efficacy of TAK-101 applied transdermally for patients with ...

4. celiac.org celiac.org/2023/06/20/celiac-disease-foundation-research-partner-takeda-garners-recognition-for-three-potential-therapies/

Celiac Disease Foundation Research Partner Takeda ... A recent clinical trial found that TAK-101 significantly reduced the immune response to gluten following gluten ingestion relative to the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33722583/

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in ... TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/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

Dose-Ranging Study of the Efficacy and Safety of TAK-101 ... 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 ...

7. gastrojournal.org gastrojournal.org/article/S0016-5085(21)00521-7/fulltext

TAK-101 Nanoparticles Induce Gluten-Specific Tolerance ... TAK-101 was well tolerated in patients with celiac disease undergoing oral gluten challenge, and prevented immune activation and small ...