TAK-101 for Celiac Disease

Recruiting at 116 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

98 Participants Needed

Trial Summary

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.

How is the drug TAK-101 different from other treatments for celiac disease?

TAK-101 (CNP-101) is unique because it is designed to specifically target the immune response to gluten, potentially offering a novel approach compared to the standard gluten-free diet, which is currently the only treatment for celiac disease. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a drug called TAK-101, given through an IV, to help adults with celiac disease who still have symptoms despite following a gluten-free diet. The drug aims to reduce these symptoms by changing how the immune system reacts to gluten. TAK-101 is designed to induce gluten-specific tolerance by encapsulating gluten protein in negatively charged nanoparticles. Participants will receive the drug at different times and doses to see how well it works and how safe it is.

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Intestinal Cellular Biomarkers of Mucosal Lesion Progression in Pediatric Celiac Disease. [2021]

2. United States 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. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Antibody Profile, Gene Expression and Serum Cytokines in At-Risk Infants before the Onset of Celiac Disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Value of IgA tTG in Predicting Mucosal Recovery in Children With Celiac Disease on a Gluten-Free Diet. [2021]