Last reviewed · How we verify

NCT03875729: PROTECT

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

Completed Phase 3 Results posted Last updated 24 April 2024
What this trial tests

Phase 3 trial testing teplizumab in Type 1 Diabetes Mellitus in 328 participants. Completed in 1 May 2023.

Timeline
5 April 2019
Primary endpoint
1 May 2023
1 May 2023

Quick facts

Lead sponsorProvention Bio, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment328
Start date5 April 2019
Primary completion1 May 2023
Estimated completion1 May 2023
Sites62 locations across France, Belgium, United Kingdom, Germany, Hungary, Poland, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Provention Bio, Inc. — full company profile →

Who can join

Adults 8 to 17, any sex, with Type 1 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in C-peptide ln(AUC+1) Standardized by Duration of the Mixed Meal Tolerance Test (MMTT) Primary · Baseline to Week 78

The area under the concentration-time curve (AUC) of C-peptide was measured after a 4-hour mixed meal tolerance test (MMTT) and is a measure of endogenous insulin production and β cell function. The AUC was computed using the trapezoidal rule and standardized by the duration of the MMTT test, i.e., AUC was divided by the last blood sample collection time (240 minutes or the last collection time for 4h MMTT).

Intent-to-treat
GroupValue95% CI
Placebo-0.2112-0.2437 – -0.1786
Teplizumab-0.0859-0.1090 – -0.0628
Per Protocol
GroupValue95% CI
Placebo-0.2185-0.2501 – -0.1869
Teplizumab-0.0800-0.1030 – -0.0570
Average Daily Exogenous Insulin Use Secondary · Week 78

The average daily insulin use was calculated based on participants who have at least 3 days of insulin use recorded in the dairy for the Week 78 visit.

Intent-to-treat
GroupValue95% CI
Placebo0.5930.470 – 0.716
Teplizumab0.4630.363 – 0.562
Per Protocol
GroupValue95% CI
Placebo0.6130.538 – 0.687
Teplizumab0.4460.390 – 0.502
Change in Glycated Hemoglobin (HbA1c) Levels (%) Secondary · Baseline to Week 78

Change in percentage (%) glycated hemoglobin (HbA1c)

Intent-to-treat
GroupValue95% CI
Placebo-1.89-2.16 – -1.62
Teplizumab-1.98-2.17 – -1.78
Per Protocol
GroupValue95% CI
Placebo-1.94-2.21 – -1.67
Teplizumab-2.07-2.27 – -1.87
Time in Range for Glycemia Control Secondary · Week 78

Time in range (%) for glycemia control was assessed using Continuous Glucose Monitoring (CGM). Time in range was defined as daily average percentage of time a participant's glucose is \>= 70 mg/dL and \<=180 mg/dL. Time in range was calculated based on participants who had at least 3 days of CGM data recorded for Week 78 visit with a range of at least 8 hours on a given day.

Intent-to-treat
GroupValue95% CI
Placebo62.6557.38 – 67.92
Teplizumab67.3663.70 – 71.03
Per Protocol
GroupValue95% CI
Placebo61.4456.50 – 66.38
Teplizumab67.6164.09 – 71.14
Rate of Clinically Important Hypoglycemic Events Secondary · During the entire study (from the first dose to the last study contact, up to 78 Weeks)

Rate = clinically important hypoglycemic events/patient-year. A clinically important episode was defined as a blood glucose value of \<54 mg/dL (3.0 mmol/L) (i.e., Level 2 Hypoglycemia, International Hypoglycemia Study Group, 2017) or a hypoglycemia event of severe cognitive impairment requiring external assistance (such as seizure, syncope, severe confusion with or without a confirmatory low blood glucose reading) (i.e., Level 3 Hypoglycemia, International Hypoglycemia Study Group 2017). Event rate was calculated for each participant as number of events / total study follow-up time. Total stu

Intent-to-treat
GroupValue95% CI
Placebo4.243.06 – 5.89
Teplizumab4.683.70 – 5.91
Per protocol
GroupValue95% CI
Placebo4.633.31 – 6.49
Teplizumab5.043.94 – 6.44
Number of Participants With Adverse Events of Special Interest (AESIs) Secondary · During the entire study (from the first dose to the last study contact, up to 78 Weeks)

AESIs are defined in the protocol and categories in the statistical analysis plan. Participants with multiple events are counted only once for each preferred term and category.

Treatment-emergent AESI
GroupValue95% CI
Placebo24
Teplizumab63
Participants with at least one >= grade 3 infection
GroupValue95% CI
Placebo2
Teplizumab1
Participants with at least one acute mononucleosis-like illness
GroupValue95% CI
Placebo3
Teplizumab17
Participants with at least one lymphoma or other malignancy, including benign tumors
GroupValue95% CI
Placebo1
Teplizumab2
Participants with at least one instance of severe hypoglycemic event
GroupValue95% CI
Placebo18
Teplizumab29
Participants with at least one >=grade 3 liver function abnormality
GroupValue95% CI
Placebo0
Teplizumab8
Participants with at least one >= grade 3 thrombocytopenia
GroupValue95% CI
Placebo0
Teplizumab0
Participants with at least one >= grade 3 neutropenia
GroupValue95% CI
Placebo0
Teplizumab7
Teplizumab Serum Concentrations Secondary · Pre-dose samples collected on Days 1, 4, 9, 12 and 28 for each of the two treatment courses, and one post-dose sample collected on Day 9 during the first treatment course.

PK samples were collected prior to dosing except for Day 9 in Course 1. An additional PK sample was collected 45 minutes after infusion on Day 9 in Course 1. Concentration values below Lower Limit of Quantification (2.50 ng/mL) were set to zero for summary statistics. Course 2 day numbers were set relative to the first day of dosing, regardless of normal or modified dosing schedule.

Course 1, Day 1
GroupValue95% CI
Teplizumab7.4271± 628.114
Course 1, Day 4
GroupValue95% CI
Teplizumab70.4769± 50.767
Course 1, Day 9
GroupValue95% CI
Teplizumab250.3928± 44.677
Course 1, Day 9 post-dose
GroupValue95% CI
Teplizumab636.4390± 33.171
Course 1, Day 12
GroupValue95% CI
Teplizumab305.6569± 47.048
Course 1, Day 28
GroupValue95% CI
Teplizumab25.0317± 79.953
Course 2, Day 1
GroupValue95% CI
Teplizumab5.5433± 522.457
Course 2, Day 4
GroupValue95% CI
Teplizumab82.0166± 50.333
Anti-teplizumab Antibody (ADA) Titers After Treatment Courses Secondary · Baseline through 78 Week

Baseline was defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.

Baseline
GroupValue95% CI
Teplizumab65.81± 182.3
Week 2
GroupValue95% CI
Teplizumab177.22± 278.2
Week 4
GroupValue95% CI
Teplizumab817.08± 275.0
Week 8
GroupValue95% CI
Teplizumab1040.58± 239.1
Week 26 Day 182
GroupValue95% CI
Teplizumab834.86± 226.1
Week 26 Day 187
GroupValue95% CI
Teplizumab807.26± 681.6
Week 27
GroupValue95% CI
Teplizumab9257.15± 222.3
Week 30
GroupValue95% CI
Teplizumab9985.29± 218.7
Incidence of Anti-drug Antibodies (ADA) After Treatment Courses Secondary · From baseline through Week 78

Baseline is defined as the most recent value collected prior to the first dose of study drug. Week 26 Day 187 and Weeks 27 and 34 are planned for subjects under the normal dosing schedule. Week 52 Day 369 and Weeks 53, 56, and 60 are planned for subjects under the modified dosing schedule.

Baseline
GroupValue95% CI
Teplizumab15
Teplizumab200
Week 2
GroupValue95% CI
Teplizumab182
Teplizumab25
Week 4
GroupValue95% CI
Teplizumab178
Teplizumab26
Week 8
GroupValue95% CI
Teplizumab175
Teplizumab31
Week 26 Day 182
GroupValue95% CI
Teplizumab139
Teplizumab53
Week 26 Day 187
GroupValue95% CI
Teplizumab130
Teplizumab40
Week 27
GroupValue95% CI
Teplizumab167
Teplizumab8
Week 30
GroupValue95% CI
Teplizumab169
Teplizumab7

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events = from the first dose of study drug administration through the end of the study, up to 78 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 6/111 (5%)
Deaths: 0/111
Teplizumab
Serious: 12/217 (6%)
Deaths: 0/217

Serious adverse events (15 terms)

ReactionSystemPlaceboTeplizumab
Cytokine release syndromeImmune system disorders
Suicidal ideationPsychiatric disorders
GastroenteritisInfections and infestations
ConcussionInjury, poisoning and procedural complications
PalpitationCardiac disorders
SyncopeNervous system disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Suicide attemptPsychiatric disorders
AnxietyPsychiatric disorders
NephrolithiasisRenal and urinary disorders
Device related bacteraemiaInfections and infestations
HypoglycaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Other adverse events (41 terms — click to expand)

ReactionSystemPlaceboTeplizumab
HypoglycaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Lymphocyte count decreasedInvestigations
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
White blood cell count decreasedInvestigations
LymphopeniaBlood and lymphatic system disorders
COVID-19Infections and infestations
Upper respiratory tract infectionInfections and infestations
Abdominal painGastrointestinal disorders
Neutrophil count decreasedInvestigations
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Aspartate Aminotransferase increasedInvestigations
ChillsGeneral disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
NasopharyngitisInfections and infestations
HypotensionVascular disorders
PruritusSkin and subcutaneous tissue disorders
Cytokine release syndromeImmune system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ProteinuriaRenal and urinary disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
TachycardiaCardiac disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Rash macularSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
GastroenteritisInfections and infestations
DermatitisSkin and subcutaneous tissue disorders

Most-reported serious reactions: Cytokine release syndrome, Suicidal ideation, Gastroenteritis, Concussion, Palpitation, Syncope, Vomiting, Constipation.

Data from ClinicalTrials.gov NCT03875729 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  3. Antibodies to watch in 2023.
    Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
  4. Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes.
    Ramos EL, Dayan CM, Chatenoud L, Sumnik Z, et al · · 2023 · cited 163× · PMID 37861217 · DOI 10.1056/nejmoa2308743
  5. Current and future therapies for type 1 diabetes.
    von Scholten BJ, Kreiner FF, Gough SCL, von Herrath M. · · 2021 · cited 85× · PMID 33595677 · DOI 10.1007/s00125-021-05398-3
  6. Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function.
    Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, et al · · 2023 · cited 76× · PMID 37607392 · DOI 10.2337/dc23-0675
  7. Inhibitory receptor agonists: the future of autoimmune disease therapeutics?
    Grebinoski S, Vignali DA. · · 2020 · cited 45× · PMID 32619929 · DOI 10.1016/j.coi.2020.06.001
  8. Evolving Antibody Therapies for the Treatment of Type 1 Diabetes.
    Ke Q, Kroger CJ, Clark M, Tisch RM. · · 2020 · cited 23× · PMID 33679717 · DOI 10.3389/fimmu.2020.624568

Verify or expand the search:

Other trials of teplizumab

Trials testing the same drug.

Other recruiting trials for Type 1 Diabetes Mellitus

Currently open trials in the same condition.

Other Provention Bio, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03875729.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing