Safety Profile

TZIELD SAFETY PROFILE (TN-10)

Common adverse reactions* 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

In the TN-10 trial, greater incidences of adverse reactions were observed in TZIELD-treated patients vs placebo-treated patients1:

  • 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.

Adverse reactions observed in TZIELD-treated pediatric patients (8 years and older) were consistent with those reported in TZIELD-treated adults.1

LYMPHOPENIA IN TN-10

Plus Sign Icon
Most instances of lymphopenia with TZIELD recovered by Week 6.1
T-Cell Icon
Lymphopenia occurred in absence of T cell depletion.1
Not Commonly Associated With The Symptomatic Reactivation of EBV or CMV
TZIELD was not commonly associated with the symptomatic reactivation of EBV or CMV.2,3‖

CMV=cytomegalovirus; EBV=Epstein-Barr virus.

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

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

Average absolute lymphocyte counts began to recover at Day 5 and returned to baseline by Week 6 in most patients1,2

"In TN-10 Trial: Average Absolute Lymphocyte Counts In Treatment Groups (TZIELD and placebo) During First 6 Weeks After Initiating Treatment" Chart"In TN-10 Trial: Average Absolute Lymphocyte Counts In Treatment Groups (TZIELD and placebo) During First 6 Weeks After Initiating Treatment" Chart

‖Adapted from Herold KC, et al. Means and confidence intervals are shown.

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.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.1

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

The safety profile of TZIELD was also evaluated in a pooled analysis of >750 patients across 5 controlled, clinical studies.1

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 days1

See dosing and administration
 

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.

Down Arrow Icon
 

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.
  • Hypersensitivity Reactions: Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients. If severe hypersensitivity reactions occur, discontinue TZIELD and treat promptly.
  • Vaccinations: The safety of immunization with live-attenuated (live) vaccines in TZIELD-treated patients has not been studied. TZIELD may interfere with immune response to vaccination and decrease vaccine efficacy. Administer all age-appropriate vaccinations prior to starting TZIELD.
    • Administer live vaccines at least 8 weeks prior to treatment. Live vaccines are not recommended during treatment, or up to 52 weeks after treatment.
    • Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment. Inactivated vaccines are not recommended during treatment or 6 weeks after completion of treatment.
Adverse reactions

Most common adverse reactions (>10%) were lymphopenia, rash, leukopenia, and headache.

Use in Specific Populations
  • Pregnancy: May cause fetal harm.
  • Lactation: A lactating woman may consider pumping and discarding breast milk during and for 20 days after TZIELD administration.

Before prescribing TZIELD, please see full Prescribing Information, including patient selection criteria, and Medication Guide.

REFERENCES
1. TZIELD Prescribing Information. Provention Bio, Inc.
2. Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. N Engl J Med. 2019;381(7):603-613.
3. Data on file. Provention Bio, Inc.
Provention Bio and the Provention Bio logo are the registered trademarks of Provention Bio, Inc.
© 2022 Provention Bio, Inc. All rights reserved. PM-TZI-086v1.0PM-TZI-083v1.0