Safety profile of TZIELD

The most common adverse reactions (>10%) reported were lymphopenia, rash, leukopenia, and headache.1

Actor portrayal

COMMON ADVERSE REACTIONS

Common adverse reactions (ARs)* in the TN-10 trial1†

Adverse
Reactions
Lymphopenia
Rash ‡
Leukopenia
Headache
Neutropenia
Alanine aminotransferase increase
Nausea
Diarrhea
Nasopharyngitis
Placebo
(N=32)
6%
0%
0%
6%
3%
3%
3%
0%
0%
TZIELD
(N=44)
73%
36%
21%
11%
5%
5%
5%
5%
5%

*Adverse reactions that occurred in 2 or more TZIELD-treated patients.1

†That occurred during treatment and through 28 days of the last TZIELD administration.1

‡Composite of rash-related terms including rash erythematous, rash macular, rash papular, rash maculo-papular, rash pruritic.1



Greater incidences of ARs observed in TZIELD-treated patients vs placebo-treated patients recorded throughout the study1,2:

  • Cytokine release syndrome (2% vs 0%, respectively)
  • Serious infections§ (9% vs 0%, respectively)
  • Hypersensitivity reactions; serum sickness (2% vs 0%, respectively)
  • Lymphopenia (73% vs 6%, respectively)
  • Neutropenia (7% vs 3%, respectively)

§Serious infections included cellulitis, gastroenteritis, pneumonia, and wound infection anytime during or after the first dose of study treatment.1

Download the TZIELD
Safety Summary
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Study details for TN-10
Study design1
The safety and efficacy of TZIELD was investigated in a randomized, double-blind, event-driven, placebo-controlled study in 76 patients, 8 to 49 years of age with Stage 2 T1D, defined as having 2 or more pancreatic islet autoantibodies* and dysglycemia on oral glucose tolerance testing. In this study, Stage 2 patients were randomized to receive TZIELD (N=44) or placebo (N=32) once daily, by intravenous infusion for 14 days.
Primary endpoint1,2
The primary efficacy endpoint in this study was the time from randomization to Stage 3 T1D diagnosis. The primary analysis was conducted when at least 40 Stage 3 T1D diagnoses were made.
*Glutamic acid decarboxylase 65 autoantibody (GADA), insulin autoantibody (IAA), insulinoma-associated antigen 2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), islet cell autoantibody (ICA).1

LYMPHOPENIA IN TN-10

Lymphopenia in TN-10 trial

Medical recovery icon

Most instances of lymphopenia with TZIELD recovered by Week 6.1

Icon of a T cell and a shield

Lymphopenia occurred in absence of T cell depletion.1

Crossed-out virus icon

TZIELD was not commonly associated with the symptomatic reactivation of EBV or CMV.3*

Monitor white blood cell counts during the treatment period. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, discontinue TZIELD.1

CMV=cytomegalovirus; EBV=Epstein-Barr virus.

*One TZIELD-treated patient in Study TN-10 reported symptoms consistent with reactivation of EBV.3

VIEW EBV AND CMV DATA

In TN-10 trial: average absolute lymphocyte counts in treatment groups (TZIELD and placebo) during first 6 weeks after initiating treatment1,3†

ENLARGE CHART
†
Adapted from Herold KC et al. Means and confidence intervals are shown.

WARNINGS & PRECAUTIONS

Additional warnings and precautions

Cytokine release syndrome (CRS)
Premedicate, monitor liver enzymes, discontinue in those that develop elevated alanine aminotransferase or aspartate aminotransferase more than 5 times the upper limit of normal, and if severe CRS develops consider temporarily pausing dosing. CRS manifestations in TZIELD-treated patients included fever, nausea, fatigue, headache, myalgia, arthralgia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), and increased total bilirubin.1

Serious infections
Use of TZIELD is not recommended in patients with active serious infection or chronic infection. Monitor for signs and symptoms of infection during and after TZIELD treatment. If a serious infection develops, discontinue TZIELD.1

Vaccinations
Administer all age-appropriate vaccinations prior to starting TZIELD. See recommendations regarding live-attenuated, inactivated, and mRNA vaccines.1

Hypersensitivity reactions
If severe hypersensitivity reactions occur, discontinue TZIELD and treat promptly. Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting, and bronchospasm occurred in TZIELD-treated patients.1

See WARNINGS AND PRECAUTIONS (section 5.0) in the Prescribing Information for TZIELD to learn more.

Words that read &quot;The safety of TZIELD was studied in a larger pooled analysis!&quot; over the TZIELD icon.

POOLED SAFETY

Pooled safety analysis of 5 controlled clinical studies

In the pooled analysis, adverse reactions were evaluated in 773 TZIELD-treated patients, and 245 patients received placebo or standard of care (1 study in patients with Stage 2 T1D [Study TN-10], 3 placebo-controlled studies in an unapproved population, and 1 open-label standard-of-care controlled study of TZIELD in an unapproved population).1

TZIELD is given once daily for 14 consecutive days.

Dosing
 

INDICATION

TZIELD is a CD3-directed monoclonal antibody indicated to delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D.

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
  • Cytokine Release Syndrome (CRS): CRS occurred in TZIELD-treated patients during the treatment period and through 28 days after the last drug administration. Prior to TZIELD treatment, premedicate with antipyretics, antihistamines and/or antiemetics, and treat similarly if symptoms occur during treatment. If severe CRS develops, consider pausing dosing for 1 day to 2 days and administering the remaining doses to complete the full 14-day course on consecutive days; or discontinue treatment. Monitor liver enzymes during treatment. Discontinue TZIELD treatment in patients who develop elevated alanine aminotransferase or aspartate aminotransferase more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN.
  • Serious Infections: Use of TZIELD is not recommended in patients with active serious infection or chronic infection other than localized skin infections. Monitor patients for signs and symptoms of infection during and after TZIELD administration. If serious infection develops, treat appropriately, and discontinue TZIELD.
  • Lymphopenia: Lymphopenia occurred in most TZIELD-treated patients. For most patients, lymphocyte levels began to recover after the fifth day of treatment and returned to pretreatment values within two weeks after treatment completion and without dose interruption. Monitor white blood cell counts during the treatment period. If prolonged severe lymphopenia develops (<500 cells per mcL lasting 1 week or longer), discontinue TZIELD.
REFERENCES
1. TZIELD Prescribing Information. Provention Bio, Inc.2. Data on file. Provention Bio, Inc.3. Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381(7):603-613.
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