At-Risk for Type 1 Diabetes Extension Study (TN-10 Extension)

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: teplizumab 1 mg/mL; Biological: teplizumab

• Registration Number: NCT04270942
• Lead Sponsor: Provention Bio, a Sanofi Company

Brief Summary

This study was an extension of the NIH-sponsored At-Risk (TN-10) type 1 diabetes study (NCT 01030861). Teplizumab-treated and placebo-treated participants in the NIH trial who developed clinical type 1 diabetes after the conclusion of that trial, were eligible to enroll and receive teplizumab treatment within one year of diagnosis of clinical type 1 diabetes.

Detailed Description

The study was a single-arm, multicenter, open-label clinical trial. All participants received a 12-day course of teplizumab given through daily IV infusion and were followed for 78 weeks.

The purpose of this study was to evaluate the safety and tolerability of teplizumab treatment, administered intravenously (IV) to participants in the NIH-sponsored trial who have developed type 1 diabetes and were able to start teplizumab treatment within 1 year of diagnosis of type 1 diabetes. Whether teplizumab treatment reduced the loss of insulin-producing pancreatic beta cells were evaluated.

Study Timeline

• Study First Submitted: 2020-02-10
• Study First Submitted QC: 2020-02-12
• Study First Posted: 2020-02-17
• Study Start: 2020-02-26
• Primary Completion: 2024-01-22
• Study Completion: 2024-01-22
• Status Verified: 2025-01
• Results First Submitted: 2025-01-20
• Results First Submitted QC: 2025-01-20
• Last Update Submitted: 2025-01-20
• Results First Posted: 2025-02-12
• Last Update Posted: 2025-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Previous participant in the TN-10 study
2. Participant had received a diagnosis of type 1 diabetes after the conclusion of the TN-10 study, according to the criteria from the American Diabetes Association (ADA).
3. Participant was able to initiate teplizumab treatment required in this study within 1 year of type 1 diabetes diagnosis.
4. Participant was willing to forego other forms of experimental treatment during the entire study.
5. Participant and/or guardian had given informed consent and assent as applicable.

Exclusion Criteria

1. Had an active infection and/or fever.
2. Had a history of or serologic evidence at screening of current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
3. An individual who had a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Teplizumab treated	teplizumab 1 mg/mL	Administration of teplizumab by intravenous infusion for 12 consecutive days
Teplizumab treated	teplizumab	Administration of teplizumab by intravenous infusion

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Events of Special Interest (TEAESIs) and Treatment-emergent Serious Adverse Events (TESAEs)	From the first dose of study drug administration (Day 1) up to approximately 78 weeks	An AE was any untoward medical occurrence in a participant or clinical study participant,temporally associated with use of study dose,whether or not considered related to study dose.AESI was any AE that met any of following:All \>=Grade 3 infections (including all opportunistic infections);acute mononucleosis-like illness;lymphomas or other malignancies;severe hypoglycemic episode;\>=Grade 3 liver function abnormalities, thrombocytopenia, neutropenia or rash;\>= Grade 4 allergic/hypersensitivity reaction (anaphylaxis) or cytokine-release syndrome; lymphocyte count \<500/cubic millimeter for 7 days or longer. An SAE was as any untoward medical occurrence that,at any dose:resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization,resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or any other medically important event.A TEAE was any AE which started during or after the first dose of teplizumab.

Secondary Outcome Measures

Name	Time	Method
Serum Concentration Immediately Prior to Administration of the Next Dose (Ctrough) of Teplizumab at Day 364	Pre-dose on Day 364	Blood samples were collected for evaluation of pharmacokinetic (PK) data.
Average Daily Use of Exogenous Insulin at Week 78	Week 78	The average daily insulin use was calculated based on participants who had at least 3 days of insulin use recorded in the diary for the Week 78 visit.
Number of Participants With Anti-drug Antibodies (ADA) Against Teplizumab	Up to Day 364	Blood samples were collected for the evaluation of ADA against teplizumab.
Area Under the Time-Versus-Concentration Curve (AUC) of C-peptide After a 4-hour (4h) Mixed Meal Tolerance Test (MMTT) at Week 78	Week 78	The AUC of C-peptide was measured after a 4-hour MMTT as a measure of assessing endogenous insulin production and beta cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test for the analysis.
Glycated Hemoglobin (HbA1c) Levels at Week 78	Week 78	Blood samples were collected for evaluation of HbA1c.
Number of Participants With Severe Hypoglycemic Episodes	From the first dose of study drug administration (Day 1) up to approximately 78 weeks	The severity of a hypoglycemia event was identified by the Investigator and classified according to National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 as follows: * Grade 3 hypoglycemia: 30-39 milligram/deciliter (mg/dL) (1.7-2.1 millimole \[mmol\]/L). This is considered severe or medically significant but not immediately life-threatening. Hospitalization or prolongation of hospitalization is likely indicated. It is considered disabling and limits self-care.; * Grade 4 hypoglycemia: \<=29 mg/dL (1.6 mmol/L). This is considered life threatening (seizures) with urgent intervention indicated.; * Grade 5 hypoglycemia: Hypoglycemia resulting in death. Hypoglycemia \>=Grade 3 was considered as severe hypoglycemia.
Number of Participants With Change in Cluster of Differentiation (CD)8+ TIGIT+ KLRG1+ T Cells	From the first dose of study drug administration (Day 1) up to approximately 78 weeks	CD8+ TIGIT+ KLRG1+ T cells were measured using flow cytometry.

Trial Locations

Locations (5)

Barbara Davis Center for Diabetes Site Number : 04; 🇺🇸 Aurora, Colorado, United States

Yale University School of Medicine Site Number : 01; 🇺🇸 New Haven, Connecticut, United States

University of Florida Site Number : 02; 🇺🇸 Gainesville, Florida, United States

Vanderbilt Univerity Medical Center Site Number : 03; 🇺🇸 Nashville, Tennessee, United States

Clinical Site; 🇺🇸 Nashville, Tennessee, United States