Resumen del Estudio
Este ensayo clínico de Fase 3 busca evaluar una terapia innovadora para niños y jóvenes (de 1 a 25 años) que han sido diagnosticados muy recientemente con Diabetes Tipo 1 en Estadio 3 (dentro de las últimas 8 semanas). El objetivo central es determinar si el medicamento biológico Teplizumab puede modificar el curso de la enfermedad autoinmune mejor que un placebo. Durante el estudio, que dura aproximadamente 18 meses, los participantes recibirán infusiones intravenosas para medir si el tratamiento logra mejorar el control del azúcar en sangre (HbA1c) y, lo más importante, si permite aumentar los días en los que el paciente no necesita inyectarse insulina con las comidas (insulina prandial), preservando así la producción natural de insulina del cuerpo.
Criterios de Elegibilidad
Resumen de Elegibilidad:Criterios de inclusión principales: Edad entre 1 y 25 años, diagnóstico de Diabetes Tipo 1 Estadio 3 confirmado hace menos de 8 semanas, presencia de autoanticuerpos positivos y niveles detectables de péptido C. Criterios de exclusión principales: Otros tipos de diabetes (Tipo 2, MODY), infecciones activas graves (VIH, Hepatitis B/C, Tuberculosis), otras enfermedades autoinmunes inestables o vacunación reciente con virus vivos.
Nota: La lista detallada se muestra en el idioma original por falta de traducción estructurada.
Criterios de Inclusión
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Participant must be 1 to 25 years of age inclusive, at the time of signing the informed consent.
- Participants diagnosed with T1D Stage 3 according to American Diabetes Association 2025 criteria
- Participants able to be randomized and initiate study drug within 8 weeks (56 days) of the Stage 3 T1D diagnosis
- Participants must be positive for at least one T1D autoantibody at screening:
- Glutamic acid decarboxylase (GAD-65),
- Insulinoma Antigen-2 (IA-2),
- Zinc-transporter 8 (ZnT8), or
- Insulin (if obtained not later than 14 days after exogenous insulin therapy initiation).
- Islet cell cytoplasmic autoantibodies (ICAs)
- Have random C-peptide level ≥0.2 nmol/L obtained at screening
- Both male and female participants are eligible.
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- A female participant is eligible to participate if she is not pregnant, and one of the following conditions applies:
- Is a woman of nonchildbearing potential (WONCBP) OR
- Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1% during the study intervention period (to be effective before starting the intervention) and for at least 30 days after the last administration of study intervention.
- A WOCBP must have a negative highly sensitive pregnancy test at screening (serum) and within 24 hours (urine or serum as required by local regulations) before the first administration of study intervention.
- Lactating woman must interrupt breastfeeding and pump and discard breast milk during and for 20 days after last administration of study intervention.
- Capable of giving signed informed consent as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Criterios de Exclusión
- Participant has diabetes other than autoimmune T1D that includes but is not limited to genetic forms of diabetes, maturity-onset diabetes of the young (MODY), diabetes secondary to medications or surgery and type 2 diabetes by judgement of the Investigator.
- Participant has an active serious infection and/or fever ≥38.5°C (101.3°F) within the 48 hours prior to the first dose (except if localized skin infection), or has chronic, recurrent or opportunistic infectious disease.
- At screening, participant has laboratory or clinical evidence of acute or clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV).
- At screening, participant has positive serology for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV).
- Participant has evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and/or TB testing. Blood testing (eg, QuantiFERON® TB Gold test) is strongly preferred; if not available, any local approved TB test is allowed.
- Has other autoimmune diseases, (eg, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus etc), except clinically stable autoimmune thyroid disease, or controlled celiac disease (at discretion of Investigator).
- Any clinically significant abnormality identified either in medical/surgical history or during screening evaluation (eg, physical examination, laboratory tests, vital signs), or any adverse event (AE) during screening period which, in the judgment of the investigator, would preclude safe completion of the study or constrains efficacy assessment.
- Participant has recent or planned vaccinations as follows:
- Live-attenuated (live) vaccines (eg, varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) within the 8 weeks before first dose of the investigational medicinal product (IMP) or planned/required administration during treatment or up to 26 weeks after last IMP administration in any treatment course
- Inactivated or mRNA vaccines within 2 weeks before the first dose of IMP or planned required administration during treatment or up to 6 weeks after last IMP administration in any treatment course.
- Current or prior use (within 30 days before screening) of any anti-hyperglycemic agents other than insulin
- Past (within 30 days prior to screening) or current administration of any treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status (including but not limited to oral, inhaled or systemically injected steroids with duration \>14 days, adrenocorticotropic hormone, verapamil).
- Past systemic immunosuppression medicine or immune modulatory biologic therapy (such as monoclonal antibodies), within 3 months or 5 half-lifes (whichever is longer) prior to dosing.
- Current or prior (within 30 days before screening) use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
- Participant has previously received teplizumab or other anti-CD3 treatment.
- Other medications not compatible or interfering with IMP at discretion of Investigator.
- Current enrollment OR past participation in another investigational study in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within the last 8 weeks or 5 half-lifes, whichever is longer, prior to screening.
- Participant has any of the following laboratory parameters, at screening prior to first dose:
- Lymphocyte count: \<1000/µL,
- Neutrophil count: \<1500/µL,
- Platelet count: \<150,000 platelets/µL,
- Hemoglobin: \<10 g/dL,
- Aspartate aminotransferase (AST) \>2.0 × upper limit of normal (ULN),
- Alanine aminotransferase (ALT) \>2.0 × ULN,
- Total bilirubin \>1.5 × ULN with the exception of participants with the diagnosis of Gilbert's syndrome who may be eligible provided they have no other causes leading to hyperbilirubinemia