Type 1 Diabetes
Conditions
Interventions
Trial Group:Teplizumab (SAR446681) intravenous infusion: First course (Days 1-12): 106 µg/m^2 on Day 1, 425 µg/m^2 on Day 2, 850 µg/m^2 on Days 3-12
Second course (Days 182-193): 106 µg/m^2 on Day 182, 425 µg/m^2 on Day 183, 850 µg/m^2 on Days 184-193. Two courses separated by approximately 26 weeks.
Placebo Group:Matching placebo intravenous infusion: Same dose and volume as the trial group (without active ingredient Teplizumab), dosing regimen identical to the trial group (two courses separated
Sponsors
The Second Xiangya Hospital of Central South University
Eligibility
Sex/Gender
All
Age
1 Years to 25 Years
Inclusion criteria
Inclusion criteria: 1.Age:Participant must be 1 to 25 years of age inclusive, at the time of signing the informed consent.Note: Participants less than 8 years of age will only be able to be included once 1-year safety data for this age category will become available from another pediatric trial (PETITE-T1D; NCT05757713). 2.Type of participant and disease characteristics:(1)Participants diagnosed with T1D Stage 3 according to American Diabetes Association 2025 criteria.(2)Participants able to be randomized and initiate study drug within 8 weeks (56 days) of the Stage 3 T1D diagnosis (the 8 weeks may be extended to within 12 weeks of diagnosis in case a mandatory live vaccine must be administered.(3) Participants must be positive for at least one T1D autoantibody at screening: 1) Glutamic acid decarboxylase (GAD-65), 2) Insulinoma Antigen-2 (IA-2), 3) Zinc-transporter 8 (ZnT8), or 4) Insulin (if obtained not later than 14 days after exogenous insulin therapy initiation). 5) Islet cell cytoplasmic autoantibodies (ICAs) Note: Documented positive T1D autoantibody(ies) obtained prior to screening are also acceptable.(4)Have random C-peptide level >=0.2 nmol/L obtained at screening Note: For children less than 3 years of age, any detectable random C-peptide at screening is acceptable for the inclusion. 3.Sex, contraceptive/barrier method and pregnancy testing requirements/breastfeeding:(1) Male participants Not applicable. (2) Female participants - Contraceptive use by women of childbearing potential (WOCBP) 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) as defined in Appendix 4: Contraceptive and barrier guidance (Section 10.4). OR Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of <1%, as described in Appendix 4 Contraceptive and barrier guidance (Section 10.4) 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. Note: If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. - Lactating woman must interrupt breastfeeding and pump and discard breast milk during and for 20 days after last administration of study intervention. 4.Informed Consent:Capable of giving signed informed consent as described in Appendix 1 (Section 10.1.3) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Note: For minor participants, a specific ICF must also be signed by the participant’s legally authorized representative (LAR).
Exclusion criteria
Exclusion criteria: 1.Medical conditions:(1) 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.(2)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.(3) At screening, participant has laboratory or clinical evidence of acute or clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV).(4) At screening, participant has positive serology for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV).(5)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.(6) 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).(7)Any clinically significant abnormality identified either in medical/surgical history or during screening evaluation (eg, physical examination, laboratory tests, vital signs), or any AE during screening period which, in the judgment of the Investigator, would preclude safe completion of the study or constrains efficacy assessment. 2.Prior/concomitant therapy:(1) Participant has recent or planned vaccinations as follows: 1) 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. 2) 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.(2) Current or prior use (within 30 days before screening) of any anti-hyperglycemic agents other than insulin.(3) 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).(4)Past systemic immunosuppression medicine or immune modulatory biologic therapy (such as monoclonal antibodies), within 3 months or 5 half-lives (whichever is longer) prior to dosing.(5)Current or prior (within 30 days before screening) use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).(6) Participant has previously received teplizumab or other anti-CD3 treatment.(7) Other medications not compatible or interfering with IMP at discretion of Investigator. 3.Prior/concurrent clinical study experience: Current enrollment OR past participation in another investigational study in whic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in glycated hemoglobin (HbA1c) from baseline to week 52;Total days without prandial insulin use from baseline to week 52;Change in mean C-peptide concentration after 2-hour mixed meal tolerance test (MMTT) stimulation (calculated by area under the curve [AUC]) from baseline to week 52 in participants aged >=5 years; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in mean C-peptide concentration after 2-hour MMTT stimulation (calculated by AUC) from baseline to week 52;Proportion of participants with positive C-peptide response (C-peptide peak concentration >=0.2 nmol/L after 2-hour MMTT stimulation) at week 52;Proportion of participants with HbA1c <=6.5% and insulin dose <=0.25 IU/kg/day at week 52;Change in time in range (TIR) (70–180 mg/dL) assessed by continuous glucose monitoring (CGM) from baseline to week 52;Rate of hypoglycemia events (grade 2 and 3 according to American Diabetes Association criteria) per participant-year during the period from baseline to week 52; | — |
Countries
China
Contacts
Public ContactZhou Zhiguang
The Second Xiangya Hospital of Central South University
Outcome results
None listed