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

An Open-Label Study to Evaluate the Safety of Teplizumab (PRV-031) in At-Risk Relatives Who Develop Type 1 Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: teplizumab 1 mg/mL

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Site
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Diabetes Site Number : 04
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Clinical Site
    • New Haven, Connecticut, United States, 06511
      • Yale University School of Medicine Site Number : 01
  • Florida
    • Gainesville, Florida, United States, 32610
      • Clinical Site
    • Gainesville, Florida, United States, 32610
      • University of Florida Site Number : 02
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Clinical Site
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univerity Medical Center Site Number : 03

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teplizumab treated; Administration of teplizumab by intravenous infusion for 12 consecutive days	Drug: teplizumab 1 mg/mL; Solution for infusion administered as IV infusion (anti-CD3 humanized monoclonal antibody). Cumulative dose: 9 mg/m2. Day 1: 106 μg/m2, Day 2: 425 μg/m2, Days 3-12: 850 μg/m2 daily; Other Names: PRV-031, Tzield

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Events of Special Interest (TEAESIs) and Treatment-emergent Serious Adverse Events (TESAEs)	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.	From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration Immediately Prior to Administration of the Next Dose (Ctrough) of Teplizumab at Day 364	Blood samples were collected for evaluation of pharmacokinetic (PK) data.	Pre-dose on Day 364
Number of Participants With Anti-drug Antibodies (ADA) Against Teplizumab	Blood samples were collected for the evaluation of ADA against teplizumab.	Up to Day 364
Area Under the Time-Versus-Concentration Curve (AUC) of C-peptide After a 4-hour (4h) Mixed Meal Tolerance Test (MMTT) at 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.	Week 78
Glycated Hemoglobin (HbA1c) Levels at Week 78	Blood samples were collected for evaluation of HbA1c.	Week 78
Average Daily Use of Exogenous Insulin at 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.	Week 78
Number of Participants With Severe Hypoglycemic Episodes	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.	From the first dose of study drug administration (Day 1) up to approximately 78 weeks
Number of Participants With Change in Cluster of Differentiation (CD)8+ TIGIT+ KLRG1+ T Cells	CD8+ TIGIT+ KLRG1+ T cells were measured using flow cytometry.	From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Collaborators and Investigators

• Sponsor: Provention Bio, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Type 1 diabetes; T1D; Teplizumab; New onset type 1 diabetes; Stage 3; Recent-onset type 1 diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: PRV-031-002; SFY18115 (Other Identifier: Sanofi Identifier)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No