A study to investigate efficacy and safety of teplizumab compared with placebo in participants 1 to 25 years of age with Stage 3 Type 1 Diabetes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

22 Dec 2025 → ongoing

Decision date (initial)

2025-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-519494-19-00

WHO UTN

U1111-1306-7316

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Safety

To demonstrate superiority of teplizumab versus (vs) placebo on glycemic control or prandial insulin independency over 52 weeks

Secondary objectives 6

1. To evaluate efficacy of teplizumab vs placebo on endogenous insulin secretion in participants 5 years and older
2. To evaluate efficacy of teplizumab vs placebo on glycemic control in all participants
3. To evaluate efficacy of teplizumab vs placebo on reducing hypoglycemia in all participants
4. To evaluate the safety and tolerability of teplizumab vs placebo in participants with recently diagnosed Stage 3 type 1 diabetes (T1D)
5. To characterize pharmacokinetics (PK) of teplizumab
6. To evaluate the potential for immunogenicity of teplizumab

Conditions and MedDRA coding

Nutritional and metabolic diseases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Participant must be 1 to 25 years of age inclusive, at the time of signing the informed consent.
2. Participants diagnosed with T1D Stage 3 according to American Diabetes Association 2025 criteria
3. Participants able to be randomized and initiate study drug within 8 weeks (56 days) of the Stage 3 T1D diagnosis
4. 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)
5. Have random C-peptide level ≥0.2 nmol/L obtained at screening
6. Both male and female participants are eligible.
7. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
8. 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
9. 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.
10. Lactating woman must interrupt breastfeeding and pump and discard breast milk during and for 20 days after last administration of study intervention.
11. 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. Note: For minor participants, a specific ICF must also be signed by the participant’s legally authorized representative (LAR).

Exclusion criteria 16

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 adverse event (AE) during screening period which, in the judgment of the investigator, would preclude safe completion of the study or constrains efficacy assessment.
8. 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.
9. Current or prior use (within 30 days before screening) of any anti-hyperglycemic agents other than insulin
10. 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).
11. 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.
12. Current or prior (within 30 days before screening) use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
13. Participant has previously received teplizumab or other anti-CD3 treatment.
14. Other medications not compatible or interfering with IMP at discretion of Investigator.
15. 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.
16. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. For United States (US) and non-European Union (EU) countries: Glycated hemoglobin (HbA1c) change from baseline
2. For US and non-EU countries: Total number of days without prandial insulin use
3. For EU countries: Change from baseline in mean 2 hours mixed meal tolerance test (MMTT) stimulated C-peptide concentration, calculated from Area Under the Curve (AUC) in participants 5 years and older
4. For EU countries: HbA1c change from baseline
5. For EU countries: Total number of days without prandial insulin use

Secondary endpoints 9

1. Change from baseline in mean 2 hours MMTT stimulated C-peptide concentration, calculated from AUC
2. Participants remaining C-peptide positive (2 hours MMTT stimulated peak C-peptide concentration ≥0.2 nmol/L)
3. Incidence of participants with HbA1c ≤6.5% and requiring ≤0.25 IU/kg/day of insulin
4. Change from baseline in Time-in-Range (TIR) (70-180 mg/dL blood glucose) assessed by continuous glucose monitoring (CGM)
5. Number of level 2 and 3 (according to American Diabetes Association) hypoglycemic events per participant year (event rates)
6. Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and TEAEs leading to treatment discontinuation
7. Teplizumab PK parameters: Maximum concentration of teplizumab [Cmax]
8. Teplizumab PK parameters: Area under the curve [AUC] and [AUClast]
9. Incidence of antidrug-antibodies (ADAs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 8

Locations

10 EU/EEA countries · 77 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 213 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications