A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease

Inclusion Criteria:

• Participants must be 18 to 75 years of age inclusive, at the time of signing theinformed consent.

• Participants with physician-diagnosed celiac disease with documented history ofbiopsy-proven celiac disease confirmed by medical records or physician statement.

• Participants who have self-reported attempt to maintain a GFD (and confirmed viaquestionnaire) for at least 12 consecutive months and must be willing to maintaintheir current diet for the duration of study participation.

• Participants have an adequate comprehension of a GFD as assessed by theInvestigator.

• Participants willing to undergo all assessments in the protocol, including 2esophagogastroduodenoscopies with duodenal biopsies.

• Participants who completed CDSD with ≥ 75% compliance from screening untilrandomization.

• During screening, participants must have at least one gastrointestinal symptom (i.e., diarrhea, abdominal pain, bloating, or nausea) of moderate or greaterseverity, as measured by the CDSD Gastrointestinal Domain, on at least 3 days out ofany consecutive 7-day period considered by the investigator to be related to glutenexposure (i.e., due to celiac disease). The symptom can vary, but severity must bemoderate or greater on three or more days. Participants must meet symptom criteriato undergo baseline esophagogastroduodenoscopy (EGD).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• A diagnosis of any severe complication of celiac disease, such as refractory celiacdisease type 1 (RCD I) requiring immune suppressive medication, or type 2 (RCD II),enteropathy associated T-cell lymphoma (EATL), ulcerative jejunitis, or recent (within 12 months of screening) GI perforation.

• Presence of other active inflammatory GI disorders, including but not limited to thefollowing: inflammatory bowel disease, eosinophilic esophagitis, diverticulitis,helicobacter infection, gastroenteritis or colitis, and microscopic colitis (requiring treatment) in the 6 months before screening. A history of treated erosiveesophagitis is not an exclusion. Abnormalities found during baseline EGD or biopsythat are consistent with an inflammatory GI disorder other than celiac disease areexclusionary.

• Presence of other systemic autoimmune diseases including scleroderma, psoriatic orrheumatoid arthritis, and lupus. Participants with thyroid disease that has beenwell-controlled for at least 6 months, prior to screening, and participants withwell-controlled type 1 diabetes (glycosylated hemoglobin < 9 % and nohospitalization or emergency room visit in the last 12 months for hyperglycemia orhypoglycemia) can be included per investigator judgement.

• Known or suspected severe enteric infection (viral, bacterial, or parasitic) within 6 months before screening. Severe enteric infection is defined as requiring a visitto the emergency room, hospitalization, or treatment with antibiotics oranti-infectives due to infection. Non-enteric viral infections, either resolved orwell-controlled are not exclusionary.

• Any active or chronic infection including helminthic infection requiring systemictreatment within 4 weeks prior to screening (1 week in the event of superficial skininfections).

• Known history of or suspected significant current immunosuppression or hyposplenism,including history of invasive opportunistic or invasive helminthic infectionsdespite infection resolution or otherwise recurrent infections of abnormal frequencyor prolonged duration.

• Any malignancies or history of malignancies prior to enrollment (except fornon-melanoma skin cancer that has been excised and completely cured for more than 5years prior to enrollment).

• History of solid organ or stem cell transplant.

• Ongoing use, or use in the 3 months before screening, of medications known to causevillus abnormalities (eg, mycophenolate mofetil, azathioprine, methotrexate,olmesartan (other angiotensin receptor blockers are allowed), CTLA4 inhibitors, andPD-1/PD-L1 inhibitors).

• Ongoing chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) of more than 2doses per week, except acetylsalicylic acid/aspirin ≤100 mg daily for prophylacticuse.

• Any ongoing treatment with systemic immunosuppressants, systemic corticosteroids, oruse of oral budesonide in the 12 weeks before screening.

• Ongoing use of over-the-counter digestive enzymes or supplements, other thanlactase, including those for gluten digestion and oral pharmaceutical probioticsupplements. Probiotics in foods (e.g., yogurt) are permitted.

• Concurrent participation in any other clinical study, including non-interventionalstudies.

• Prior administration of investigational agents to treat celiac disease within 5half-lives of any agent, or one year from any tolerogenic agent.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.