Summary of safety profile Adverse reactions in patients treated with Tzield were evaluated in a pool of adult and paediatric patients who participated in five controlled clinical studies (one study in patients with Stage 2 T1D [Study TN-10], three placebo-controlled studies in an unapproved population (Stage 3 T1D), and one open-label standard-of-care controlled study of Tzield in an unapproved population (Stage 3 T1D)).
Lymphopenia, leukopenia, neutropenia, blood bicarbonate decreased, and rash were the most frequently reported adverse reactions, which occurred at a higher frequency in the teplizumab group compared to the control group. Tabulated list of adverse reactions The adverse reactions occurring in ≥5% of patients in the pooled safety analysis of clinical studies are shown in Table 1 per System Organ Class presented by frequency categories: very common: (≥1/10), common: (≥1/100 to <1/10), uncommon: (≥1/1000 to <1/100), rare: (≥1/10,000 to <1/1000), very rare: (<1/10,000), not known: (cannot be estimated from the available data).
Table 1. Adverse reactions occurring in ≥5% of patients in the pooled safety analysis of clinical studies. System Organ Class Frequency Category Very common Common Not known Blood and lymphatic system disorders Lymphopenia, Leukopenia, Neutropenia, Haemoglobin decreased, Thrombocytopenia Immune system disorders Cytokine release syndrome Nervous system disorders Headache Respiratory, thoracic and mediastinal disorders Nasopharyngitis Gastrointestinal disorders Nausea Diarrhoea Vomiting Skin and subcutaneous tissue disorders Rash, Pruritus Urticaria Rash Pruritic General disorders and administration site conditions Pyrexia Chills Fatigue, Pain, Illness Investigations Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood bicarbonate decreased, Blood calcium decreased Description of selected adverse reactions Cytokine Release Syndrome (CRS) In Study TN-10, CRS was reported in 2% of patients treated with Tzield compared to 0% of patients in the placebo group.
4). 5% were 5-10 times ULN. Serious Infections In Study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% (4/44) of patients treated with Tzield compared to 0% (0/32) of patients treated with placebo any time during or after the first dose of study treatment.
Lymphopenia In Study TN-10, lymphopenia was reported in 73% of patients treated with Tzield compared to 6% of patients in the placebo group. 4). Rash and Hypersensitivity Reactions Hypersensitivity reactions were reported with Tzield in Study TN-10.
Serum sickness was observed in 2% (1/44) of patients treated with Tzield compared to 0% (0/32) of patients in the placebo group. 5 months. In the pool of 5 clinical trials of patients: • Anaphylaxis (with hypoxia and bronchospasm) was observed in one patient treated with Tzield who was hospitalised.
3% patients treated with Tzield, compared to 0% of patients in the control group. 6% of patients treated with Tzield and 0% of patients in the control group. • Rash was observed in 35% of patients treated with Tzield compared to 10% of patients in the control group.
3% (2/791) of patients treated with Tzield had a serious rash compared to 0% (0/245) of patients in the placebo group. 2% of patients in the control group. Other Adverse Reactions Haemoglobin Decreased and Thrombocytopenia In the pool of 5 clinical trials of patients, haemoglobin decreased was reported in 28% of patients treated with Tzield compared to 22% of patients in the placebo group, and thrombocytopenia was reported in 22% of patients treated with Tzield compared to 10% of patients in the placebo group during the 14-day treatment course; recovery occurred within 2 to 4 weeks of treatment.
5% of patients treated with Tzield discontinued treatment due to haemoglobin less than 85 g/L (or a decrease of more than 20 g/L to a value less than 100 g/L), and 1% discontinued Tzield due to platelet count less than 50 x 109 platelets/L.
Liver Enzyme and Bilirubin Elevations Liver enzyme and bilirubin elevations were observed in patients treated with Tzield, both in the context of CRS and in patients without CRS. 8% of patients in the control group. Most liver enzyme elevations were transient and resolved 1-2 weeks after treatment; 98% resolved by follow-up week 14.
Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of Tzield or of other teplizumab products.
In the placebo-controlled study in […]