Drug Trials Snapshots: TZIELD
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the TZIELD Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
TZIELD (teplizumab-mzwv)
TEE-zeeld
Provention Bio, Inc.
Original Approval date: November 17, 2022
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TZIELD is a drug that is used to delay the onset of type 1 diabetes in children and adults who are at high risk for type 1 diabetes.
How is this drug used?
TZIELD is an injection given by a healthcare professional directly into a vein (intravenous infusion) once per day for 14 days.
Who participated in the clinical trials?
The FDA approved TZIELD based on evidence from one clinical trial (Study TN-10) of 76 patients at high risk of developing type 1 diabetes. Study TN-10 was conducted at 30 sites in 5 countries including the United States, Canada, Australia, the United Kingdom, and Germany.
How were the trials designed?
The effectiveness of TZIELD was investigated in a randomized, double-blind, event-driven, placebo-controlled study (Study TN-10, NCT01030861) in 76 patients, 8 to 49 years of age with stage 2 type 1 diabetes. Stage 2 type 1 diabetes was defined as having both of the following:
1. Two or more of the following pancreatic islet autoantibodies:
- Glutamic acid decarboxylase 65 (GAD) autoantibodies
- Insulin autoantibody (IAA)
- Insulinoma-associated antigen 2 autoantibody (IA-2A)
- Zinc transporter 8 autoantibody (ZnT8A)
- Islet cell autoantibody (ICA)
2. Dysglycemia on oral glucose tolerance testing
In this trial, patients were randomized to receive TZIELD or placebo once daily by intravenous infusion for 14 days. The primary endpoint in this trial was the time from randomization to development of stage 3 type 1 diabetes diagnosis.
How were the trials designed?
In addition to TN-10, the safety of TZIELD was also evaluated in a larger pool of adult and pediatric patients who participated in four controlled clinical trials (three placebo-controlled and one open-label standard-of-care controlled) in an unapproved population. In total, the clinical trials evaluated for safety included 773 subjects who received TZIELD and 245 who received placebo or control. 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, 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.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of TZIELD.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of TZIELD.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of TZIELD.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of TZIELD.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population, Study TN-10
| Demographic | TZIELD N=44 n (%) |
Placebo N=32 n (%) |
| Sex | ||
| Female | 19 (43) | 15 (47) |
| Male | 25 (57) | 17 (53) |
| Age group, years | ||
| <18 | 29 (66) | 26 (81) |
| ≥18 | 15 (34) | 6 (19) |
| Pediatric age groups, years | ||
| 8 to <11 | 10 (23) | 8 (25) |
| 11 to <14 | 10 (23) | 9 (31) |
| 14 to <18 | 9 (20) | 9 (28) |
| Race | ||
| White | 44 (100) | 30 (94) |
| Asian | 0 (0) | 1 (3) |
| Multiple | 0 (0) | 1 (3) |
| Ethnicity | ||
| Hispanic or Latino | 1 (2) | 1 (3) |
| Not Hispanic or Latino | 43 (98) | 29 (91) |
| Unknown | 0 (0) | 2 (6) |
Adapted from FDA Review and TZIELD Prescribing Information
What are the benefits of this drug?
Type 1 diabetes is a lifelong condition where your body cannot make enough insulin on its own to keep blood sugar levels normal, and you need daily insulin injections or an insulin pump. TZIELD is a prescription medicine that delays the onset of type 1 diabetes in patients who are at high risk for having the disease. A high-risk person has two or more type 1 diabetes-related autoantibodies and abnormal blood sugar levels that are not yet high enough for a diagnosis of diabetes. During the clinical trial that followed each participant for about 51 months those taking TZIELD had a 59% lower risk of developing type 1 diabetes compared to those taking placebo. Participants taking TZIELD developed type 1 diabetes generally 50 months after receiving the medication, compared to 25 months among those taking placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Primary Efficacy Endpoint Analysis Results, Efficacy Population, Study TN-10
| Parameter | TZIELD N=44 |
Placebo N=32 |
Total N=76 |
| Event numbers, n (%) | |||
| Number of patients diagnosed with T1D | 20 (45) | 23 (72) | 43 (57) |
| Number of censored patients | 24 (55) | 9 (28) | 33 (43) |
| Censored due to reaching trial end: follow-up still ongoing at cutoff date | 22 (50) | 8 (25) | 30 (39) |
| Censored due to discontinuation from study for reasons other than diagnosis | 2 (5) | 1 (3) | 3 (4) |
| Follow-up time | |||
| Median follow-up time (month) | 50.6 | 49.9 | 50.6 |
| Time to event summary statistics | |||
| Median time to T1D diagnosis (month) (95% CI) | 49.5 (32.1, NE) | 24.9 (9.5, 48.6) | 42.6 (25.9, 55.2) |
| Primary analysis: Cox proportional hazard model | |||
| Hazard ratio (95% CI) | 0.41 (0.22, 0.78) | ||
| p-value | 0.0066 | ||
Adapted from FDA Review
Figure 5. Kaplan-Meier Curve of Time to Diagnosis of Stage 3 Type 1 Diabetes in Adult and Pediatric Patients Aged 8 Years and Older With Stage 2 Type 1 Diabetes by Treatment Group, Efficacy Population, Study TN-10
TZIELD Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: TZIELD worked similarly in males and females.
- Race: The number of participants of races other than White was small; therefore, differences in how TZIELD worked among races could not be determined.
- Age: TZIELD worked similarly in all age groups.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Primary Efficacy Endpoint Analysis Results by Sex and Age, Efficacy Population, Study TN-10
| Subgroup | Hazard Ratio (95% Credible Interval)a |
| Sex | |
| Female (N=34) | 0.22 (0.07, 0.68) |
| Male (N=42) | 0.58 (0.25, 1.31) |
| Age group, years | |
| 8 to <11 (N=18) | 0.37 (0.09, 1.46) |
| 11 to <14 (N=19) | 0.34 (0.12, 0.97) |
| 14 to <18 (N=18) | 0.62 (0.21, 1.82) |
| ≥18 (N=21) | 0.41 (0.14, 1.15) |
Source: Adapted from FDA Review
a Estimates and credible intervals for treatment effect include relevance of outcomes from other subgroups.
What are the possible side effects?
TZIELD may cause serious side effects including:
- Cytokine release syndrome with signs and symptoms including fever, headache, fatigue, muscle and joint pain, and increased liver enzymes in your blood
- Decrease in white blood cells that can affect your body’s ability to fight infections
- Serious allergic reactions (hypersensitivity)
The most common side effects of TZIELD are lymphopenia (decrease in a certain type of white blood cells called lymphocytes), rash, leukopenia (decrease in the total number of white blood cells), and headache.
What are the possible side effects (results of trials used to assess safety)?
Table 4. Common Adverse Reactions in Adult and Pediatric Patients Aged 8 Years and Older With Stage 2 Type 1 Diabetes, Safety Population, Study TN-10b
| Adverse Reaction | TZIELD N=44 % |
Placebo N=32 % |
| Lymphopenia | 73 | 6 |
| Rashc | 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 |
Source: TZIELD Prescribing Information
a That occurred during treatment and through 28 days after the last study drug administration
b Adverse reactions that occurred in 2 or more TZIELD-treated subjects
c Composite of rash-related terms including rash erythematous, rash macular, rash papular, rash maculo-papular, and rash pruritic
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: There were no differences in side effects by race, although the safety data among patients of races other than White and Asian was limited.
- Age: People who are at high risk for type 1 diabetes are generally children and younger adults. There were no differences in side effects by age. Studies to assess side effects generally did not include those 65 years of age and older.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Adverse Events by Sex, 14-Day Treatment Period, Safety Population, Pooled Analysis1
| Event | TZIELD, N=773 | Control, N=245 | ||
| Female n/Ns (%) |
Male n/Ns (%) |
Female n/Ns (%) |
Male n/Ns (%) |
|
| Any TEAE | 276/278 (99.3) | 481/495 (97.2) | 71/93 (76.3) | 116/152 (76.3) |
| SAE | 1/278 (0.4) | 9/495 (1.8) | 1/93 (1.1) | 0/152 (0.0) |
Source: Adapted from FDA Review
1 Pooled analysis taken from full Integrated Summary of Safety (ISS), limited to adverse events reported during the 14-day course one treatment period
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; SAE, serious adverse event; TEAE, treatment-emergent adverse event
Table 6. Adverse Events by Race, 14-Day Treatment Period, Safety Population, Pooled Analysis1
| Event | TZIELD, N=773 | Control, N=245 | ||||
| White n/Ns (%) |
Asian n/Ns (%) |
All Others n/Ns (%) |
White n/Ns (%) |
Asian n/Ns (%) |
All Others n/Ns (%) |
|
| Any TEAE | 546/554 (98.6) | 193/200 (96.5) | 18/19 (94.7) | 139/188 (73.9) | 44/51 (86.3) | 4/6 (66.7) |
| SAE | 9/554 (1.6) | 1/200 (0.5) | 0/19 (0.0) | 1/188 (0.5) | 0/51 (0.0) | 0/6 (0.0) |
Source: Adapted from FDA Review
1 Pooled analysis taken from full Integrated Summary of Safety (ISS), limited to adverse events reported during the 14-day course one treatment period
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; SAE, serious adverse event; TEAE, treatment-emergent adverse event
Table 7. Adverse Events by Age, 14-Day Treatment Period, Safety Population, Pooled Analysis1
| Event | TZIELD, N=773 | Control, N=245 | ||
| <18 Years n/Ns (%) |
≥18 Years n/Ns (%) |
<18 Years n/Ns (%) |
≥18 Years n/Ns (%) |
|
| Any TEAE | 468/477 (98.1) | 289/296 (97.6) | 121/165 (73.3) | 66/80 (82.5) |
| SAE | 7/477 (1.5) | 3/296 (1.0) | 0/165 (0.0) | 1/80 (1.3) |
Source: Adapted from FDA Review
1 Pooled analysis taken from full Integrated Summary of Safety (ISS), limited to adverse events reported during the 14-day course one treatment period
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; SAE, serious adverse event; TEAE, treatment-emergent adverse event
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
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