Trial Outcomes & Findings for At-Risk for Type 1 Diabetes Extension Study (TN-10 Extension) (NCT NCT04270942)

Last Updated: 2025-02-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Results posted on

2025-02-12

Participant Flow

The study was conducted in the United States from 26-Feb-2020 to 22-Jan-2024.

A total of 6 participants from the TN-10 study (NCT01030861) who developed clinical (stage 3) type 1 diabetes (T1D) after the completion of that study were enrolled in this study. All participants received teplizumab in this study within 1 year of diagnosis of clinical T1D.

Participant milestones

Participant milestones
Measure	Teplizumab Participants received teplizumab 9 milligrams per meter square (mg/m\^2) via intravenous (IV) infusion as a 12-day course (once daily) split as: Day 1: 106 micrograms (mcg)/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Overall Study STARTED	6
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Teplizumab Participants received teplizumab 9 milligrams per meter square (mg/m\^2) via intravenous (IV) infusion as a 12-day course (once daily) split as: Day 1: 106 micrograms (mcg)/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Overall Study Death	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Teplizumab n=6 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Age, Continuous	21.3 years STANDARD_DEVIATION 11.59 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab.

Outcome measures

Outcome measures
Measure	Teplizumab n=6 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Events of Special Interest (TEAESIs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAE	6 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Events of Special Interest (TEAESIs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAESI	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Events of Special Interest (TEAESIs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TESAE	1 Participants

SECONDARY outcome

Timeframe: Pre-dose on Day 364

Population: The PK analysis set included all participants in the safety analysis set who had at least 1 eligible PK sample for analysis. Only those participants with data collected on Day 364 are reported.

Blood samples were collected for evaluation of pharmacokinetic (PK) data.

Outcome measures

Outcome measures
Measure	Teplizumab n=5 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Serum Concentration Immediately Prior to Administration of the Next Dose (Ctrough) of Teplizumab at Day 364	NA nanogram/milliliter (ng/mL) Standard Deviation NA NA indicates that Mean and Standard deviation could not be determined as the values were below the lower limit of quantification (LLOQ). LLOQ value was 2.50 ng/mL.

SECONDARY outcome

Timeframe: Up to Day 364

Population: The immunogenicity analysis set included all participants in the safety analysis set who had at least 1 eligible immunogenicity sample for analysis.

Blood samples were collected for the evaluation of ADA against teplizumab.

Outcome measures

Outcome measures
Measure	Teplizumab n=6 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Number of Participants With Anti-drug Antibodies (ADA) Against Teplizumab	6 Participants

SECONDARY outcome

Timeframe: Week 78

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab. Only those participants with data collected at Week 78 are reported.

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.

Outcome measures

Outcome measures
Measure	Teplizumab n=4 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Area Under the Time-Versus-Concentration Curve (AUC) of C-peptide After a 4-hour (4h) Mixed Meal Tolerance Test (MMTT) at Week 78	0.549 ln(AUC+1) (picomole/mL) Standard Deviation 0.4276

SECONDARY outcome

Timeframe: Week 78

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab. Only those participants with data collected at Week 78 are reported.

Blood samples were collected for evaluation of HbA1c.

Outcome measures

Outcome measures
Measure	Teplizumab n=4 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Glycated Hemoglobin (HbA1c) Levels at Week 78	8.50 percentage of HbA1c Standard Deviation 3.785

SECONDARY outcome

Timeframe: Week 78

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab. Only those participants with data collected at Week 78 are reported.

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.

Outcome measures

Outcome measures
Measure	Teplizumab n=4 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Average Daily Use of Exogenous Insulin at Week 78	0.54 unit/kilogram/day Standard Deviation 0.357

SECONDARY outcome

Timeframe: From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab.

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.

Outcome measures

Outcome measures
Measure	Teplizumab n=6 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Number of Participants With Severe Hypoglycemic Episodes	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug administration (Day 1) up to approximately 78 weeks

Population: The safety analysis set included all participants who received at least 1 dose of teplizumab.

CD8+ TIGIT+ KLRG1+ T cells were measured using flow cytometry.

Outcome measures

Outcome measures
Measure	Teplizumab n=6 Participants Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Number of Participants With Change in Cluster of Differentiation (CD)8+ TIGIT+ KLRG1+ T Cells	4 Participants

Adverse Events

Teplizumab

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Teplizumab n=6 participants at risk Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Psychiatric disorders Completed Suicide	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.

Other adverse events

Other adverse events
Measure	Teplizumab n=6 participants at risk Participants received teplizumab 9 mg/m\^2 via IV infusion as a 12-day course (once daily) split as: Day 1: 106 mcg/m\^2, Day 2: 425 mcg/m\^2 and Days 3 to 12: 850 mcg/m\^2.
Blood and lymphatic system disorders Leukopenia	33.3% 2/6 • Number of events 6 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Blood and lymphatic system disorders Lymphopenia	50.0% 3/6 • Number of events 12 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Cardiac disorders Bradycardia	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Gastrointestinal disorders Nausea	50.0% 3/6 • Number of events 5 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Chills	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Fatigue	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Feeling Hot	16.7% 1/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Infusion Site Pruritus	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Pain	16.7% 1/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
General disorders Pyrexia	33.3% 2/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Immune system disorders Cytokine Release Syndrome	16.7% 1/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Infections and infestations Covid-19	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Infections and infestations Cellulitis	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Infections and infestations Nasopharyngitis	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Infections and infestations Pharyngitis	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Infections and infestations Upper Respiratory Tract Infection	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Investigations Alanine Aminotransferase Increased	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Investigations Aspartate Aminotransferase Increased	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Investigations Blood Lactate Dehydrogenase Increased	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Investigations Eosinophil Count Increased	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Nervous system disorders Headache	66.7% 4/6 • Number of events 10 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Nervous system disorders Neuralgia	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Psychiatric disorders Anxiety	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Respiratory, thoracic and mediastinal disorders Pharyngeal Erythema	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Skin and subcutaneous tissue disorders Pruritus	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Skin and subcutaneous tissue disorders Rash	33.3% 2/6 • Number of events 2 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Skin and subcutaneous tissue disorders Rash Macular	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.
Vascular disorders Hypertension	16.7% 1/6 • Number of events 1 • From the first dose of study drug administration (Day 1) up to approximately 78 weeks The safety analysis set included all participants who received at least 1 dose of teplizumab.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER