TZIELD

TZIELD is an FDA-registered drug product whose active ingredient is TEPLIZUMAB-MZWV. It is labelled by Provention Bio, Inc. taken by intravenous and marketed as a human prescription drug product. Identifiers on file: NDC 73650-316, application BLA761183, label effective 20260814. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing TEPLIZUMAB-MZWV are most often described in connection with: pediatric patients, aged years, onset stage, type diabetes, year age, decline endogenous, insulin production, recently diagnosed. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE TZIELD is indicated to [see Dosage and Administration (2.1) ]: Delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D. Delay the decline in endogenous insulin production in pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. This indication is approved under accelerated approval based on evidence of reduced C-peptide decline [see Clinical Studies (14.2) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: There is limited evidence of safety and effectiveness in patients aged 45 years and older with Stage 2 T1D. TZIELD is not effective as a disease modifying therapy in non-autoimmune dysglycemic conditions . TZIELD is a CD3-directed antibody indicated to: ( 1 ) Delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D. Delay the decline in endogenous insulin production in pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. This indication is approved under accelerated approval based on evidence of reduced C-peptide decline. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use : ( 1 ) There is limited evidence of safety and effectiveness in patients aged 45 years and older with Stage 2 T1D. TZIELD is not effective as a disease modifying therapy in non-autoimmune dysglycemic conditions.

2 DOSAGE AND ADMINISTRATION Confirm Stage 2 T1D by documenting at least two positive pancreatic islet autoantibodies in those who have dysglycemia without overt hyperglycemia using an oral glucose tolerance test (OGTT) or alternative method if appropriate and OGTT is not available ( 2.1 ). In patients who meet criteria for a diagnosis of Stage 2 T1D ensure the patient's diagnosis confirms an autoimmune origin and does not suggest insulin resistance due to obesity, type 2 diabetes (T2D) or dysglycemia due to other forms of diabetes. Confirm Stage 3 T1D by documenting at least one positive pancreatic islet cell autoantibody and peak C-peptide ≥0.2 pmol/mL on a mixed-meal tolerance test (MMTT) or alternative method if appropriate and MMTT is not available ( 2.1 ). Prior to initiating TZIELD, obtain a complete blood count and liver enzyme tests and evaluate patients for active EBV and CMV infection, including assessment of viral load (e.g., polymerase chain reaction testing). Consider expert consultation for appropriate laboratory and clinical evaluation to assess for active EBV or CMV infection. Use of TZIELD is not recommended in patients with certain laboratory abnormalities. TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection) ( 2.2 ). Premedicate with: (1) a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, (2) an antihistamine, and (3) consider use of an antiemetic before each TZIELD dose for at least the first 5 days of the treatment course ( 2.3 ). Administer TZIELD by intravenous infusion once daily for 14 days (Stage 2) or 12 days (Stage 3). See full prescribing information for the recommended dosage, dosing schedule, minimum infusion duration according to age, and recommendations regarding missed doses ( 2.4 , 2.5 ). See full prescribing information for recommendations on: monitoring lymphocyte counts, liver enzymes, bilirubin, and symptoms of viral reactivation; and discontinuing treatment ( 2.6 ). Must dilute TZIELD in 0.9% Sodium Chloride Injection, USP. See full prescribing information for detailed preparation and administration instructions ( 2.7 ). 2.1 Patient Selection Patients with Stage 2 T1D Select adult and pediatric patients 1 year of age and older with Stage 2 T1D for TZIELD treatment to delay the onset of Stage 3 T1D based on the confirmation of: At least two positive pancreatic islet cell autoantibodies, and Dysglycemia without overt hyperglycemia using an oral glucose tolerance test (OGTT): If an OGTT is not available, an alternative method for diagnosing dysglycemia without overt hyperglycemia may be appropriate. In adults aged 18 years or older , recommend following the definition of dysglycemia used in clinical trials to diagnose dysglycemia prior to use of TZIELD due to the lack of specificity of other measures [see Clinical Studies (14.1) ] . Ensure the patient's diagnosis confirms an autoimmune origin and does not suggest insulin resistance due to obesity, type 2 diabetes (T2D) or dysglycemia due to other forms of diabetes. These may include, but are not limited to, genetic forms of diabetes, maturity-onset diabetes of the young (MODY), latent autoimmune diabetes in adults (LADA), or diabetes secondary to medications or surgery. Patients with Stage 3 T1D Select pediatric patients aged 8 to 17 years recently diagnosed (within the last 8 weeks) with Stage 3 T1D for TZIELD treatment to delay the decline in endogenous insulin production based on confirmation of both of the following: At least one positive pancreatic islet cell autoantibody Peak C-peptide ≥0.2 pmol/mL on a mixed-meal tolerance test (if a mixed meal tolerance test is not available, an alternative method for measuring peak C-peptide ≥0.2 pmol/mL may be appropriate). 2.2 Laboratory and Infection Evaluation, and Vaccination Prior to Initiation Prior to initiating TZIELD, obtain a complete blood count and liver enzyme tests. Use of TZIELD is not recommended in patients with the following conditions [see Warnings and Precautions (5.3) , Adverse Reactions (6.1) ] : Lymphocyte count less than 1,000 lymphocytes/mcL Hemoglobin less than 10 g/dL Platelet count less than 150,000 platelets/mcL Absolute neutrophil count less than 1,500 neutrophils/mcL Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (ULN) or bilirubin greater than 1.5 times ULN Active serious infection or chronic active infection other than localized skin infections [see Warnings and Precautions (5.3) ]. Prior to initiating treatment, evaluate patients for active EBV and CMV infection, including assessment of viral load [e.g., polymerase chain reaction (PCR) testing]. Consider expert consultation for appropriate laboratory and clinical evaluation to assess for active EBV or CMV infection. Use of TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection). [see Warnings and Precautions (5.1) ] . Administer all age-appropriate vaccinations prior to starting TZIELD [see Warnings and Precautions (5.6) ] : Administer live-attenuated (live) vaccines at least 8 weeks prior to TZIELD treatment. Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment. 2.3 Important Premedication Instructions Prior to each of the first 5 days of TZIELD infusion [see Warnings and Precautions (5.2) ] : Premedicate with a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen Premedicate with an antihistamine, and Consider premedication with an antiemetic If needed, administer additional premedication doses. 2.4 Recommended Dosage and Administration Body Surface Area Dosage Calculation The dosage of TZIELD is based on body surface (BSA) area, which is calculated using the Mosteller formula, below: Using the patient's BSA, calculate the dose based on treatment day: Dose (mcg) = Daily dosage (mcg/m 2 ) × BSA (m 2 ) Recommended Dosage and Administration in Patients with Stage 2 T1D Administer TZIELD once daily for 14 consecutive days using BSA-based dosing per the schedule below: Day(s) Daily Dosage Day 1 65 mcg/m 2 Day 2 125 mcg/m 2 Day 3 250 mcg/m 2 Day 4 500 mcg/m 2 Days 5 through 14 1,030 mcg/m 2 Administer TZIELD by intravenous infusion over a minimum of: 30 minutes in adult and pediatric patients aged 8 years and older. 2 hours in pediatric patients aged 1 to less than 8 years [see Clinical Pharmacology (12.3) ] . Recommended Dosage and Administration in Patients with Stage 3 T1D Initiate treatment as soon as possible following Stage 3 T1D diagnosis but no later than 8 weeks from diagnosis. Administer TZIELD by intravenous infusion over a minimum of 30 minutes, once daily for 12 consecutive days for each treatment course, for a total of two treatment courses, using the BSA-based dosing schedule below: Day(s) Daily Dosage Day 1 106 mcg/m 2 Day 2 425 mcg/m 2 Days 3 through 12 850 mcg/m 2 Second treatment Course: Administer the second 12-day treatment course 6 months after the first treatment course. If the second course is delayed, administer the second treatment course within 6 to 12 months after the first treatment course. Image 2.5 Recommendations Regarding Missed Doses If a planned TZIELD infusion is missed, administer the missed dose as soon as possible and all remaining doses on consecutive days to complete the 14 total dose regimen in patients with Stage 2 T1D or each of the two 12-day treatment courses in patients with Stage 3 T1D. Do not administer two doses on the same day. 2.6 Recommended Monitoring During Treatment with TZIELD Monitor lymphocyte count regularly (every 2–3 days) during TZIELD infusion and monitor for lymphocyte recovery following completion of TZIELD. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, permanently discontinue TZIELD. Monitor patients for signs and symptoms of viral reactivation during TZIELD treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD [see Warnings and Precautions (5.1) ] . Monitor liver enzymes and bilirubin during treatment. Discontinue TZIELD treatment in patients who develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN [see Warnings and Precautions (5.2) ] . 2.7 Preparation and Administration Instructions Read this entire section carefully before preparing TZIELD. Must dilute TZIELD prior to use. This requires the preparation of 100 mcg/mL dilution followed by the preparation of an infusion solution. Start the infusion after preparation is complete. If the TZIELD infusion solution is not used immediately, store as instructed per corresponding infusion preparation method. The following are preparation and administration instructions based on BSA dosing requirements [see Dosage and Administration (2.4) ] : TZIELD 100 mcg/mL Dilution Preparation: Prior to dilution, inspect TZIELD visually before use (the supplied solution is clear and colorless). Do not use TZIELD if particulate matter or coloration is seen. Prepare TZIELD using aseptic technique. Each vial is intended for one-time use only, discard any unused portion. If the calculated dose is: 2,000 mcg or less, then prepare: One sterile syringe (polypropylene (PP), polycarbonate (PC) or glass) or One sterile glass vial with 18 mL of 0.9% Sodium Chloride Injection or One ≤50 mL polyvinylchloride (PVC) with di-(2-ethylhexyl)phthalate (DEHP) infusion bag with 18 mL of 0.9% Sodium Chloride Injection. Greater than 2,000 mcg, then prepare: Two sterile syringes (PP, PC or glass) or Two sterile glass vials with 18 mL of 0.9% Sodium Chloride Injection or Two ≤50 mL PVC with DEHP infusion bags with 18 mL of 0.9% Sodium Chloride Injection. Remove the cap from the TZIELD vial – this is the preparation start time. Remove 2 mL of TZIELD from the single-dose vial and slowly add to the sterile syringes (PP, PC or glass), glass vial or PVC with DEHP infusion bag containing 18 mL of 0.9% Sodium Chloride Injection. Mix gently by slowly swirling the vial or rocking the infusion bag or syringe. The resulting 20 mL diluted TZIELD solution contains 100 mcg/mL of teplizumab-mzwv. If preparing a dose greater than 2,000 mcg, repeat the above process with second TZIELD vial and the glass vial, or PVC with DEHP infusion bag or syringe (PP, PC or glass) containing 18 mL of 0.9% Sodium Chloride Injection. TZIELD Infusion Solution Preparation: Calculate the volume of TZIELD 100 mcg/mL dilution needed for the infusion. Volume of 100 mcg/mL dilution (mL) = Dose (mcg) 100 mcg/mL There are two different methods for preparation of the infusion: infusion bag (Method 1) or syringe (Method 2, for syringe pump infusion). Use the appropriate steps below depending on the selected method. Method 1: Infusion bag for intravenous administration: Using an appropriately sized syringe [see Compatible Materials for Administration (2.8) ] , withdraw the volume of TZIELD 100 mcg/mL dilution required for that day's calculated dose (for a calculated dose 2,000 mcg or less) or from both prepared 100 mcg/mL dilutions (for a calculated dose more than 2,000 mcg) [see TZIELD 100 mcg/mL Dilution Preparation ] . Discard unused portion of remaining TZIELD dilution in the syringe, sterile glass vial or PVC with DEHP infusion bag. Slowly add contents of the syringe containing the TZIELD dose to a PVC with DEHP infusion bag containing 25 mL of 0.9% Sodium Chloride Injection ( for a calculated dose more than 2,000 mcg, add the cumulative volume for the calculated dose to a single infusion bag ). Gently rock the infusion bag to ensure that the solution mixes sufficiently. Do not shake. Infusion bag administration: Prime the IV infusion set with the TZIELD infusion solution. Do not waste any infusion solution during the priming process. Infusion administration has a minimum duration of: 30 minutes in adult and pediatric patients aged 8 years and older 2 hours in pediatric patients aged 1 to less than 8 years Rate may be slowed for patient's tolerability. After infusion, flush the IV set with a volume of 0.9% Sodium Chloride Injection greater than or equal to the priming volume, to ensure full dose is administered. Same infusion rate should be used for flushing. If the TZIELD infusion solution is not used immediately, store at room temperature between 15°C to 25°C (59°F to 77°F). Discard if the infusion is unable to be completed within 6 hours of preparation. Method 2: Syringe for intravenous infusion via syringe pump: Requires an appropriately sized sterile syringe (up to 60 mL) [i.e., infusion syringe] which is compatible with available syringe pump. The syringe pump should support rates as low as 1 mL/hour [see Compatible Materials for Administration (2.8) ] . The final concentration range is 15 mcg/mL to 60 mcg/mL with a maximum infusion volume of 60 mL. To fit technical constraints of syringe pump, a lower volume may be used as long as the concentration is between 15 mcg/mL and 60 mcg/mL. If the calculated dose is: 900 mcg or less: Calculate the maximum volume that can be administered for the calculated dose (based on treatment day, dose and patient BSA) using a minimum infusion concentration of 15 mcg/mL. Volume Infusion (mL) = Dose (mcg) Minimum infusion concentration 15 mcg/mL Calculate the volume of 0.9% Sodium Chloride Injection to be added to the infusion syringe: Volume 0.9% Sodium Chloride Injection (mL) = Volume Infusion (mL) - Volume 100 mcg/mL dilution (mL) Greater than 900 mcg: the maximum infusion volume is capped at 60 mL. Volume 0.9% Sodium Chloride Injection (mL) = 60 mL - Volume 100 mcg/mL dilution (mL) For all doses: Measure the appropriate volume of 0.9% Sodium Chloride Injection from above calculation into the infusion syringe. Using an appropriately sized syringe, withdraw the volume of TZIELD 100 mcg/mL dilution [see Compatible Materials for Administration (2.8) ] required for that day's calculated dose (for a calculated dose 2,000 mcg or less) and add it to the infusion syringe. For a calculated dose more than 2,000 mcg, add the cumulative volume from both prepared 100 mcg/mL dilutions to a single infusion syringe [see TZIELD 100 mcg/mL Dilution Preparation ] . Gently rock the infusion syringe to ensure that the solution mixes sufficiently. Do not shake. Syringe administration: Prime the IV extension set with the TZIELD infusion solution. Do not waste any infusion solution during the priming process. Attach infusion syringe to a syringe pump. The infusion must be administered over a minimum of: 30 minutes in adult and pediatric patients aged 8 years and older 2 hours in pediatric patients aged 1 to less than 8 years Do not manually push the syringe. Infusion administration rate may be slowed for patient's tolerability. After infusion, flush the IV extension set with a volume of 0.9% Sodium Chloride Injection greater than or equal to the priming volume at the same infusion rate to ensure full dose is administered. If the TZIELD infusion solution is not used immediately, store refrigerated at 2°C to 8°C (36°F to 46°F) for up to 12 hours, followed by a maximum of 6 hours at room temperature between 15°C to 25°C (59°F to 77°F) which includes infusion time. Discard if the infusion is unable to be completed within 15 hours of preparation. 2.8 Compatible Materials for Administration Compatibility has been demonstrated with the materials listed in Table 1. Other materials should not be used. Table 1. Compatible Materials for TZIELD Administration Step Equipment Product Contact Material Abbreviations: PP=polypropylene, PC=polycarbonate, PVC with DEHP=polyvinylchloride with di-(2-ethylhexyl)phthalate, PE=polyethylene. Initial dilution Containers PP, PC, glass, PVC with DEHP IV bag Syringes PP, PC, glass Infusion with IV bags IV bags PVC with DEHP for all doses EVA bags for doses ≥ 240 mcg Infusion sets PVC with DEHP Infusion with syringe pump Infusion dilution container Syringe: PP, PC Syringes PP, PC Infusion/extension sets PE, PVC with or without DEHP Use of in-line filter is not recommended. If necessary, use a polyethylene sulfone (PES) filter. Do not use light protected (colored) infusion sets.

4 CONTRAINDICATIONS TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection) [see Warnings and Precautions (5.1) ]. TZIELD is contraindicated in patients who are immunocompromised or have active viral infection (such as EBV or CMV infection) ( 4 ).

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the Prescribing Information: Viral Reactivation [see Warnings and Precautions (5.1) ] Cytokine Release Syndrome [see Warnings and Precautions (5.2) ] Serious Infections [see Warnings and Precautions (5.3) ] Lymphopenia [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions were lymphopenia, vomiting, rash, leukopenia, diarrhea, neutropenia, increased liver transaminase and headache ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Provention Bio, Inc. at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Placebo-Controlled Study in Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D (TN-10) The data in Table 2 are derived from the placebo-controlled study (Study TN-10) in adult and pediatric patients aged 8 years and older with Stage 2 T1D [see Clinical Studies (14.1) ]. These data reflect exposure of 44 patients of whom 93% completed the full 14-day treatment course. Table 2 presents common (≥5%) adverse reactions that occurred during treatment and through 28 days after the last study drug administration in patients with Stage 2 T1D in Study TN-10. Adverse reactions observed in pediatric patients 8 years and older who received TZIELD were consistent with those reported in adult patients in this study. Table 2. Common Adverse Reactions That occurred during treatment and through 28 days after the last study drug administration. in Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D (Study TN-10) Adverse reactions that occurred in 2 or more TZIELD-treated patients Adverse Reaction TZIELD N=44 Placebo N=32 Lymphopenia Grouped term includes other related terms 73% 6% Rash 36% 0% Leukopenia 21% 0% Headache 11% 6% Neutropenia 5% 3% Increased alanine aminotransferase 5% 3% Nausea 5% 3% Diarrhea 5% 0% Nasopharyngitis 5% 0% Placebo-Controlled Trial in Pediatric Patients Aged 8 to 17 Years with Stage 3 T1D In a 78-week placebo-controlled trial (PROTECT) in patients aged 8 to 17 years recently diagnosed with Stage 3 T1D, 328 patients were randomized to TZIELD or placebo daily by intravenous infusion for a 12-day course followed by another 12-day course 6 months later [see Clinical Studies (14.2) ]. Table 3 presents common adverse reactions (≥5%) that occurred during either of the two 12-day treatment courses and through 28 days after the last dose of study drug administration in the PROTECT trial. Table 3. Common Adverse Reactions Adverse reactions occurring in equal or more than 5% of participants in the TZIELD group, higher in TZIELD compared to placebo, in treatment course 1 through 28 days after the last dose. in Pediatric Patients Aged 8 to 17 Years with Stage 3 T1D (PROTECT Study) Adverse Reaction TZIELD n=217 Placebo n=111 Course 1 Lymphopenia Grouped term includes other related terms. 51% 3% Rash 51% 9% Leukopenia 34% 3% Nausea 34% 12% Headache 29% 16% Vomiting 26% 5% Neutropenia 23% 5% Abdominal pain 18% 11% Pyrexia 16% 3% Alanine aminotransferase increased 11% 0% Diarrhea 10% 6% Cytokine release syndrome 7% 1% Hypotension 7% 6% Aspartate aminotransferase increased 7% 1% Hemoglobin decreased 5% 4% Chills 5% 0% No new adverse reactions were observed with the second course of TZIELD treatment. Incidence rates were similar than those reported during the first treatment course. Pool of Five Controlled Clinical Studies in Stage 2 or Stage 3 T1D Adverse reactions in TZIELD-treated patients were also evaluated in a larger pool of adult and pediatric patients who participated in five controlled clinical studies (including Study TN-10 described above): One study in patients with Stage 2 T1D (Study TN-10) [see Clinical Studies (14.1) ] , Three placebo-controlled studies in patients with Stage 3 T1D, One open-label standard-of-care controlled study of TZIELD in patients with Stage 3 T1D. In this pool: 773 patients received TZIELD (44 patients with Stage 2 T1D and 729 patients with Stage 3 T1D), and 245 patients received either placebo or standard of care control (32 patients with Stage 2 T1D and 213 patients with Stage 3 T1D). In these studies, 436 patients received a 14-day dosing regimen of TZIELD with a total drug exposure that was comparable to the total drug exposure achieved with the recommended dosage [see Dosage and Administration (2.4) ] , 168 patients received a 14-day course of TZIELD with a lower total TZIELD drug exposure, and 169 patients received a 6-day course of TZIELD with a lower total TZIELD drug exposure. The mean age of TZIELD-treated patients was 17.6 years (median 15 years), 62% were less than 18 years old (40% age 12 to 17; 21% age 8 to 11), 38% were 18 years and older (36% age 18 to 34; 2% age ≥35), and 64% were male. The population was 72% White, 26% Asian, 1% Black or African American, 1% were multiple or unknown race, and less than 1% American Indian or Alaska Native; 5% were Hispanic or Latino ethnicity. Common Adverse Reactions Cytokine Release Syndrome (CRS) In Study TN-10, CRS was reported in 2% of TZIELD-treated patients compared to 0% of placebo-treated patients. In the PROTECT Study, CRS was reported in 9% of TZIELD-treated patients compared to 1% of placebo-treated patients. Of the 39 TZIELD-treated patients developed CRS (5% of all TZIELD-treated patients), in the pool of 5 clinical trials, 13% of the CRS cases were serious adverse reactions [see Warnings and Precautions (5.2) ] . Liver transaminase elevations were observed in 56% of TZIELD-treated patients who experienced CRS; 64% were up to 2.5 times ULN, 32% were more than 2.5 to 5 times ULN, and 4.5% were greater than 5 –10 times ULN. Serious Infections In Study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% (4/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients any time during or after the first dose of study treatment. In clinical trials, serious infections were reported in 3.5% of TZIELD-treated patients compared to 2% of control-treated patients any time during or after the first dose of study treatment. Rash and Hypersensitivity Reactions Hypersensitivity reactions were reported with TZIELD treatment in Study TN-10. Serum sickness was observed in 2% (1/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients. The patient who developed serum sickness had a prior history of positive anti-nuclear antibody and presented with arthralgias and elevated c-reactive protein and low C4 complement five days after completing their course of TZIELD; illness resolved in 2.5 months. In the PROTECT Study, hypersensitivity reactions were reported in 1% of TZIELD-treated patients and 0% in the placebo group. One patient in the TZIELD group experienced delayed hypersensitivity. The patient had a prior history of allergic rhinitis and presented with symptoms of rash and arthralgia 16 days after completing Course 1. The event resolved with antihistamine treatment. In the pool of 5 clinical trials of patients with Stage 2 or Stage 3 T1D: Anaphylaxis (with hypoxia and bronchospasm) was observed in one TZIELD-treated patient who was hospitalized. Angioedema (periorbital and facial) was observed in 0.3% TZIELD-treated patients, compared to 0% in control-treated patients. Peripheral and generalized edema was reported in 1.6% of TZIELD-treated patients and 0% of control-treated patients. Rash was observed in 48% of TZIELD-treated patients compared to 15% in control-treated patients, with 33 excess cases of rash per 100 patients. The majority of events of rash observed with TZIELD treatment were not serious and resolved without intervention; although 0.3% (2/773) of TZIELD-treated patients had a serious rash compared to 0% (0/245) of placebo-treated patients. Urticaria was reported in 1.9% of TZIELD-treated patients and in 1.2% of control-treated patients. Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In Study TN-10, rash occurred in 39% of TZIELD-treated patients who developed anti-teplizumab-mzwv antibodies and in 33% of TZIELD-treated patients who did not develop anti-teplizumab-mzwv antibodies [see Clinical Pharmacology (12.6) ]. In the PROTECT Study, rash occurred in 30% of TZIELD-treated patients who developed anti-teplizumab-mzwv antibodies and in 17% of TZIELD-treated patients who did not develop anti-teplizumab-mzwv antibodies [see Clinical Pharmacology (12.6) ]. Open Label Study in Pediatric Patients Age 1 to Less Than 8 Years with Stage 2 T1D The safety of TZIELD was evaluated in a non-randomized, single arm, open-label, multicenter study in 23 pediatric patients age 1 to less than 8 years with Stage 2 T1D ( PETITE-T1D Study; NCT05757713)[see Clinical Pharmacology (12.3) ]. In this trial, 87% completed the full 14-day treatment course. The median age was 4.9 years (1 patient was less than 2 years old; 52% were 2 to less than 5 years old; 44% were 5 to less than 8 years old; range 1.7 to 6.8 years) and 52% were female. The majority of the population (96%) was White and one patient (4%) was Asian; 3 patients (13%) were Hispanic or Latino ethnicity. At baseline, 87% of participants had a first-degree relative with T1D. The majority (87%) were positive for 3 or more diabetes-related autoantibodies. The most common autoantibodies were anti-insulin (87%), anti-ICA (85%), anti-GAD65 (83%), anti-ZnT8 (74%), and anti-IA2 (68%). The median HbA1c was 5.5%. Overall, the safety profile of TZIELD observed in pediatric patients less than 8 years of age with Stage 2 T1D was consistent with that observed in patients 8 years of age and older with Stage 2 T1D. The most common adverse reactions that occurred in patients less than 8 years of age were vomiting (52%) and diarrhea (30%). Other Adverse Reactions Lymphopenia In Study TN-10, lymphopenia was reported in 73% of TZIELD-treated patients compared to 6% of placebo-treated patients. The average lymphocyte count nadir occurred at Day 5 of treatment, with recovery and return to baseline by Week 6 [see Warnings and Precautions (5.4) ]. In the PROTECT Study, lymphopenia was reported in 51% of TZIELD-treated patients compared to 3% of placebo-treated patients. Lymphocyte count nadir occurred at approximately Day 4 of treatment, with recovery and return to baseline by Week 4 [see Warnings and Precautions (5.4) ]. Neutropenia In Study TN-10, neutropenia was observed in 7% of TZIELD-treated patients compared to 3% of placebo-treated patients. In the PROTECT Study, neutropenia was observed in 23% of TZIELD-treated patients compared to 5% of placebo-treated patients. Decreased Hemoglobin and Thrombocytopenia In the pool of 5 clinical trials, decreased hemoglobin was reported in 27% of TZIELD-treated patients compared to 21% of placebo-treated patients, and thrombocytopenia was reported in 13% of TZIELD-treated patients compared to 5% of placebo-treated patients during the 14-day treatment course; recovery occurred within 2 to 4 weeks of treatment. In these clinical trials, 1.8% of TZIELD-treated patients discontinued treatment due to hemoglobin less than 8.5 g/dL (or a decrease of more than 2 g/dL to a value less than 10 g/dL), and 1% discontinued TZIELD due to platelet count less than 50,000 platelets/mcL. Liver Enzyme Elevations Liver enzyme and bilirubin elevations were observed in TZIELD-treated patients, both in the context of CRS and in patients without CRS. In the pool of 5 clinical trials, ALT increased was reported in 25% of TZIELD-treated patients compared to 11% of placebo-treated patients during the 14-day treatment course. On laboratory analysis, 5.1% of TZIELD-treated patients experienced a peak ALT more than 3 times the ULN compared to 0.8% of control-treated patients. Most liver enzyme elevations were transient and resolved 1–2 weeks after treatment; 98% resolved by week 14. Procedure-Related Venous Thrombosis Venous thrombus and thrombophlebitis have been reported in patients receiving teplizumab intravenously administered via peripherally inserted central catheter (PICC). In the pool of 5 clinical trials of patients, deep vein thrombus was reported in 0.4% of TZIELD-treated patients compared to 0 placebo-treated patients. One teplizumab-treated patient (4.3%) in the PETITE-T1D study experienced a deep vein thrombosis. Other Laboratory Abnormalities In the pool of 5 clinical trials, other laboratory abnormalities including decreased bicarbonate (15% in TZIELD-treated patients, compared to 7% in placebo-treated patients) and decreased blood calcium (19% in TZIELD-treated patients, compared to 13% in placebo-treated patients) were noted.

What is TZIELD used for?
1 INDICATIONS AND USAGE TZIELD is indicated to [see Dosage and Administration (2.1) ]: Delay the onset of Stage 3 type 1 diabetes (T1D) in adult and pediatric patients 1 year of age and older with Stage 2 T1D. Delay the decline in endogenous insulin production in pediatric patients aged 8 to 17 years recently diagnosed with Stage 3 T1D. This indication is approved under accelerated approval …

Who makes TZIELD?
Provention Bio, Inc. is the labeler of record for TZIELD.

What form does TZIELD come in?
administered by intravenous. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is TZIELD prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has TZIELD been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.