Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab (PROTECT)

Provention Bio

Status and phase: Completed; Phase 3

Conditions: Type 1 Diabetes Mellitus

Treatments: Biological: Placebo; Biological: teplizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03875729

PRV-031-001

Details and patient eligibility

About

The purpose of this study is to determine whether teplizumab slows the loss of β cells and preserves β cell function in children and adolescent 8-17 years old who have been diagnosed with T1D in the previous 6 weeks..

Subjects will receive two courses of either teplizumab or placebo treatment 6 months apart.

Full description

This is a Phase 3, randomized, double-blind, placebo-controlled, multinational, multi-center study to evaluate the efficacy and safety of teplizumab, a humanized, anti-CD3 monoclonal antibody, in children and adolescents ages 8 through 17 recently diagnosed with type 1 diabetes (within 6 weeks of diagnosis). Approximately 300 participants will be randomized at a ratio of 2:1 to either the teplizumab group or the placebo group.

Teplizumab or matching placebo will be administered in two courses 6 months apart. Each course of treatment will include daily infusions for 12 days. The total study duration for each participant will be up to 86 weeks.

The primary objective is to determine whether two courses of teplizumab administered 6 months apart slows the loss of β cells and preserves β cell function over 18 months (78 weeks) in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous 6 weeks.

The secondary objectives are to evaluate improvements in key clinical parameters of diabetes management, to determine the safety and tolerability of teplizumab, and to evaluate the pharmacokinetics (PK) and immunogenicity of teplizumab

Enrollment: 328 patients

Sex: All

Ages: 8 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Is 8 to 17 years of age, inclusive, at the time of randomization/initiation of study drug administration.
2. Has received a diagnosis of type 1 diabetes (T1D) according to the criteria from the American Diabetes Association.
3. Is able to be randomized and initiate study drug within 6 weeks (42 days) of the formal T1D diagnosis.
4. Has a peak stimulated C-peptide of ≥0.2 pmol/mL from a mixed meal tolerance test (MMTT) at screening.
5. Has a positive result on testing for T1D-related autoantibodies.

Exclusion criteria

1. Has any autoimmune disease other than T1D with the exception of stable thyroid or celiac disease.
2. Has an active infection and/or fever.
3. Has 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).
4. An individual who has a medical, psychological or social condition that, in the opinion of the Principal Investigator, would interfere with safe and proper completion of the trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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328 participants in 2 patient groups, including a placebo group

Teplizumab

Experimental group

Description:

Teplizumab was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52 visit). Each course of treatment included daily infusions for 12 days. Each course included: * Day 1: 106 μg/m\^2 * Day 2: 425 μg/m\^2 * Days 3-12: 850 μg/m\^2 Total per course: 9.0 mg/m\^2 The doses of study drug were calculated based on the participant's body surface area (BSA) measured on the first day of each treatment course.

Treatment:

Biological: teplizumab

Placebo

Placebo Comparator group

Description:

Placebo was administered via intravenous infusion in two courses, with the first course starting on Day 1 (Week 1) and the second course approximately 6 months later at Day 182 (Week 26). Participants who were unable to receive the second 12-day course due to COronaVIrus Disease of 2019 (COVID-19) pandemic restrictions were given the second course at approximately 12 months (Week 52 visit). Each course of treatment included daily infusions for 12 days. The placebo solution consisted of the same formulation as the study drug but without teplizumab. Placebo was administered in the same dose volume and by the same treatment schedule as the active drug.

Treatment:

Biological: Placebo