Amlitelimab for Celiac Disease

Recruiting at 131 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must not be taking: NSAIDs, Immunosuppressants, Corticosteroids, others

Disqualifiers: Refractory celiac, Inflammatory GI, Autoimmune, others

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

Compensation: Varies

Number of Visits: 24

Duration: 28 weeks

204 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2a/b, randomized, double-blind, placebo-controlled, parallel-group, 6-arm study to evaluate the efficacy and safety of amlitelimab in adult participants with non-responsive celiac disease (NRCD) who are on a gluten free diet (GFD) with and without simulated inadvertent gluten exposure (SIGE). The primary purpose of this study is to demonstrate the efficacy of subcutaneous (SC) amlitelimab in male and female participants (aged 18 to 75 years, inclusive) with NRCD. The study will assess the effect of amlitelimab when compared to placebo on gluten induced changes in the intestinal mucosa as measured by the villous height to crypt depth (Vh:Cd) ratio. The effect of amlitelimab on participant-reported celiac signs and symptoms along with the safety, tolerability, and pharmacokinetics of amlitelimab will also be studied. Study details include: The study duration will be up to 48 weeks (including a 16-week safety follow-up period) with 10 visits for participants who opt not to enter the optional long-term extension. The study duration will be up to 172 weeks (including an 8-week safety follow-up period) with 22 visits for participants who enter the optional long-term extension. The double-blind placebo-controlled treatment duration will be up to 28 weeks.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as those known to cause villus abnormalities and ongoing use of systemic immunosuppressants or corticosteroids. If you're taking any of these, you may need to stop them before joining the trial.

How does the drug Amlitelimab differ from other treatments for celiac disease?

Amlitelimab is a novel drug being studied for celiac disease, which is currently managed primarily through a strict gluten-free diet. Unlike the dietary approach, Amlitelimab may offer a pharmacological option, potentially targeting the immune response involved in celiac disease, although specific details about its mechanism in this condition are not provided in the available research. ^{1 2 3 4 5}

Eligibility Criteria

Adults aged 18-75 with non-responsive celiac disease (NRCD) who have tried a gluten-free diet for at least a year can join. They must be willing to undergo tests including biopsies and show moderate or severe gastrointestinal symptoms related to gluten exposure.

Inclusion Criteria

I am willing to undergo all required tests, including 2 upper GI endoscopies with biopsies.

I understand what a gluten-free diet involves.

I followed through with my previous study tasks at least 75% of the time.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous amlitelimab or placebo for up to 28 weeks in a double-blind, placebo-controlled setting

28 weeks

10 visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

2 visits

Long-term extension (optional)

Participants may opt into continuation of treatment long-term

124 weeks

12 visits

Treatment Details

Interventions

• Amlitelimab

Trial Overview The trial is testing Amlitelimab, an injectable medication, against a placebo in participants with NRCD. It aims to see if the drug improves intestinal damage caused by gluten and reduces celiac symptoms compared to no treatment.

Participant Groups

Group I: Amlitelimab dose 3 + GFP Experimental Treatment 2 Interventions

Amlitelimab SC as per protocol + GFP

Group II: Amlitelimab dose 2 + GFP Experimental Treatment 2 Interventions

Amlitelimab SC as per protocol + GFP

Group III: Amlitelimab dose 1 + SIGE Experimental Treatment 2 Interventions

Amlitelimab SC as per protocol + SIGE

Group IV: Amlitelimab dose 1 + Gluten-free product (GFP) Experimental Treatment 2 Interventions

Amlitelimab SC as per protocol + GFP

Group V: Placebo + GFP Placebo Group 2 Interventions

Placebo SC as per protocol + GFP

Group VI: Placebo + SIGE Placebo Group 2 Interventions

Placebo SC as per protocol + SIGE

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a study of 209 children suspected of having coeliac disease (CD), 61.5% were diagnosed with CD, and 29% could have avoided biopsy using updated ESPGHAN guidelines based on high levels of specific antibodies.

The study found that testing for IgA tissue transglutaminase (aTTG) and IgG antibodies to deamidated gliadin (DGP) provided 100% specificity and positive predictive value for CD, suggesting that HLA typing and endomysial antibodies (EMA) may not be necessary for diagnosis in patients with high aTTG levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population. Thompson, G., Grover, Z., Loh, R., et al.[2021]

The majority of specialist pediatric gastroenterology centers in the UK (28 out of 29) have successfully implemented the no-biopsy pathway for diagnosing celiac disease in symptomatic children, aligning with the 2012 ESPGHAN guidelines.

Despite good adherence to the guidelines, there are notable variations in practices, such as the use of HLA-DQ2/DQ8 testing and the timing of gluten-free diet initiation, indicating a need for more standardized follow-up protocols and research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiac Disease Management in the United Kingdom Specialist Pediatric Gastroenterology Centers-A Service Survey. Paul, SP., Balakumar, V., Gillett, PM.[2023]

Celiac disease is an autoimmune condition triggered by gluten in genetically predisposed individuals, with a prevalence estimated between 1 in 100 and 1 in 400, and it can present either symptomatically or asymptomatically.

The only effective treatment for celiac disease is a strict gluten-free diet, which leads to clinical remission within weeks, although full recovery of the small bowel may take months to years, helping to prevent serious long-term complications like osteoporosis and cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celiac disease in children. Garnier-Lengliné, H., Cerf-Bensussan, N., Ruemmele, FM.[2015]

A 3-year-old girl with celiac disease initially improved on a gluten-free diet but later experienced abdominal pain and anorexia after 2 years.

The symptoms were linked to Helicobacter pylori gastritis, and after successful treatment to eradicate the bacteria, her symptoms resolved, highlighting the importance of monitoring for other gastrointestinal issues in celiac disease patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Celiac disease associated with Helicobacter pylori infection]. Cârdei, E., Moraru, D., Trandafir, L., et al.[2020]

HLA-DQ2 homozygosity is significantly associated with severe complications in celiac disease, such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphomas (EATL), based on a study of 43 RCD I, 43 RCD II, and 30 EATL patients compared to controls.

Identifying patients with homozygous HLA-DQ2 early could help in recognizing those at higher risk for developing these serious complications, as 97.7% of RCD II and 96.6% of EATL patients had HLA-DQ2 compared to only 28.9% in healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Al-Toma, A., Goerres, MS., Meijer, JW., et al.[2011]

References

1. England pubmed.ncbi.nlm.nih.gov

Assessment of European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines in an Australian paediatric population. [2021]

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

Celiac Disease Management in the United Kingdom Specialist Pediatric Gastroenterology Centers-A Service Survey. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Celiac disease in children. [2015]

4. Romania pubmed.ncbi.nlm.nih.gov

[Celiac disease associated with Helicobacter pylori infection]. [2020]

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

Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. [2011]