Resumen

Este es un estudio de fase 2a/b, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos con 6 brazos, para evaluar la eficacia y seguridad de amlitelimab en participantes adultos con enfermedad celíaca no respondedora (ECNR) que siguen una dieta sin gluten (DSG) con y sin exposición accidental simulada al gluten (EASG). El objetivo principal de este estudio es demostrar la eficacia de amlitelimab subcutáneo (SC) en participantes masculinos y femeninos (de 18 a 75 años, inclusive) con ECNR. El estudio evaluará el efecto de amlitelimab en comparación con placebo sobre los cambios inducidos por el gluten en la mucosa intestinal, medidos mediante la relación entre la altura de las vellosidades y la profundidad de las criptas (Vh:Cd). También se estudiarán el efecto de amlitelimab sobre los signos y síntomas celíacos notificados por los participantes, así como la seguridad, tolerabilidad y farmacocinética de amlitelimab. Detalles del estudio: La duración del estudio será de hasta 48 semanas (incluido un período de seguimiento de seguridad de 16 semanas), con 10 visitas para los participantes que opten por no ingresar a la extensión opcional a largo plazo. La duración del estudio será de hasta 172 semanas (incluido un período de seguimiento de seguridad de 8 semanas), con 22 visitas para los participantes que ingresen a la extensión opcional a largo plazo. La duración del tratamiento doble ciego controlado con placebo será de hasta 28 semanas.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
Participants with physician-diagnosed celiac disease with documented history of biopsy-proven celiac disease confirmed by medical records or physician statement.
Participants who have self-reported attempt to maintain a GFD (and confirmed via questionnaire) for at least 12 consecutive months and must be willing to maintain their current diet for the duration of study participation.
Participants have an adequate comprehension of a GFD as assessed by the Investigator.
Participants willing to undergo all assessments in the protocol, including 2 esophagogastroduodenoscopies with duodenal biopsies.
Participants who completed CDSD with ≥ 75% compliance from screening until randomization.
During screening, participants must have at least one gastrointestinal symptom (i.e., diarrhea, abdominal pain, bloating, or nausea) of moderate or greater severity, as measured by the CDSD Gastrointestinal Domain, on at least 3 days out of any consecutive 7-day period considered by the investigator to be related to gluten exposure (i.e., due to celiac disease). The symptom can vary, but severity must be moderate or greater on three or more days. Participants must meet symptom criteria to undergo baseline esophagogastroduodenoscopy (EGD).

Criterios de exclusión

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 celiac disease 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 the following: 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 erosive esophagitis is not an exclusion. Abnormalities found during baseline EGD or biopsy that are consistent with an inflammatory GI disorder other than celiac disease are exclusionary.
Presence of other systemic autoimmune diseases including scleroderma, psoriatic or rheumatoid arthritis, and lupus. Participants with thyroid disease that has been well-controlled for at least 6 months, prior to screening, and participants with well-controlled type 1 diabetes (glycosylated hemoglobin \< 9 % and no hospitalization or emergency room visit in the last 12 months for hyperglycemia or hypoglycemia) 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 visit to the emergency room, hospitalization, or treatment with antibiotics or anti-infectives due to infection. Non-enteric viral infections, either resolved or well-controlled are not exclusionary.
Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to screening (1 week in the event of superficial skin infections).
Known history of or suspected significant current immunosuppression or hyposplenism, including history of invasive opportunistic or invasive helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
Any malignancies or history of malignancies prior to enrollment (except for non-melanoma skin cancer that has been excised and completely cured for more than 5 years 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 cause villus abnormalities (eg, mycophenolate mofetil, azathioprine, methotrexate, olmesartan (other angiotensin receptor blockers are allowed), CTLA4 inhibitors, and PD-1/PD-L1 inhibitors).
Ongoing chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) of more than 2 doses per week, except acetylsalicylic acid/aspirin ≤100 mg daily for prophylactic use.
Any ongoing treatment with systemic immunosuppressants, systemic corticosteroids, or use of oral budesonide in the 12 weeks before screening.
Ongoing use of over-the-counter digestive enzymes or supplements, other than lactase, including those for gluten digestion and oral pharmaceutical probiotic supplements. Probiotics in foods (e.g., yogurt) are permitted.
Concurrent participation in any other clinical study, including non-interventional studies.
Prior administration of investigational agents to treat celiac disease within 5 half-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.

Intervenciones

drug

Amlitelimab

Pharmaceutical form: Injection solution Route of administration: SC injection

drug

Placebo

Pharmaceutical form: Injection solution Route of administration: SC injection

dietary_supplement

SIGE

Pharmaceutical form: Capsule Route of administration: Oral

dietary_supplement

Gluten-free product (GFP)

Pharmaceutical form: Capsule Route of administration: Oral

Ubicaciones

Investigational Site Number : 0320010

Quilmes, Buenos Aires, Argentina

Investigational Site Number : 0320008

San Isidro, Buenos Aires, Argentina

Investigational Site Number : 0320012

Buenos Aires, Buenos Aires F.D., Argentina

Investigational Site Number : 0320005

Rosario, Santa Fe Province, Argentina

Investigational Site Number : 0320002

San Miguel de Tucumán, Tucumán Province, Argentina

Investigational Site Number : 0320007

Buenos Aires, Argentina

Investigational Site Number : 0320009

Buenos Aires, Argentina

Investigational Site Number : 0320001

Buenos Aires, Argentina

Investigational Site Number : 0320003

Córdoba, Argentina

Estudio de fase 2a/b, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos para investigar la eficacia y seguridad de amlitelimab subcutáneo en pacientes adultos con enfermedad celíaca no respondedora como complemento a una dieta sin gluten

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Amlitelimab

Placebo

SIGE

Gluten-free product (GFP)

Ubicaciones

Investigational Site Number : 0320010

Investigational Site Number : 0320008

Investigational Site Number : 0320012

Investigational Site Number : 0320005

Investigational Site Number : 0320002

Investigational Site Number : 0320007

Investigational Site Number : 0320009

Investigational Site Number : 0320001

Investigational Site Number : 0320003

Patrocinadores