Diabetes Mellitus de tipo 1 de presentación reciente MedDRA version: 9.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus
Conditions
Interventions
Product Name: Teplizumab / MGA031 (hOKT3?1 (Ala Ala))
Product Code: MGA031
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Teplizumab
CAS Number: 876387-05-2
Current Sp
Sponsors
MacroGenics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria: 1. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria (Appendix A) 2. Written informed consent obtained from the subject (assent will be obtained for subjects under age 18 years, according to all applicable regulations) including consent for the use of research-related health information 3. Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes 4. Currently receiving insulin therapy 5. Detectable fasting or stimulated C-peptide level (above the lower limit of detection of the assay) 6. Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies: a. Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2), b. Glutamic acid decarboxylase (GAD) autoantibodies, or c. Insulin autoantibodies (if present during first 2 weeks, but not beyond 2 weeks, of insulin treatment) 7. Subjects 8?35 years old 8. Body weight >or = 36 Kg 9. BSA =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects must have none of the following: 1. Prior administration of a monoclonal antibody-within the 1 year before randomization at Study Day 0 2. Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0 3. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial 4. Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study 5. Prior murine OKT®3 treatment or other anti-CD3 treatment 6. Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion 7. Current treatment with oral antidiabetic agents 8. Current or planned therapy with inhaled insulin, if it becomes available 9. Uncompensated heart failure, fluid overload, myocardial infarction or evidence of ischemic heart disease or other serious cardiac disease as described in New York Heart Association (NYHA) Class III or IV criteria within the 12 weeks before randomization (See Appendix E) 10. History of epilepsy, cancer, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease or cerebrovascular disease 11. Untreated hypothyroidism or active Graves' disease 12. Eczema, asthma or severe atopic disease requiring treatment, including topical or inhaled corticosteroids, within the 12 weeks before randomization 13. Treatment with systemic glucocorticoid therapy by oral, intravenous (IV), intramuscular (IM), or inhaled route within 12 weeks before randomization; patients who are likely to require treatment with corticosteroids during the trial are also excluded 14. Evidence of active infection 15. Known or suspected infection with human immunodeficiency virus (HIV) 16. History of or positive tests for hepatitis A, B, C, D, or E 17. Total bilirubin > 1.5 x upper limit of normal (ULN) 18. AST or ALT > 1.5 x ULN 19. Evidence of active or latent tuberculosis (TB), which may include a positive purified protein derivative (PPD) skin test result (> or = 10 mm induration); a chest X-ray consistent with TB or household contact with a person with active TB, unless appropriate isoniazid (INH) prophylaxis for tuberculosis (TB) was previously given 20. Vaccination with a live virus within the 8 weeks before randomization or planned live virus vaccination continuing through Week 52 of the study. Vaccination with an antigen or killed organism must not be given within 8 weeks before or planned within 8 weeks after each dosing cycle 21. Any infectious mononucleosis-like illness within the 6 months before randomization 22. Serologic or clinical evidence of acute infection with Epstein-Barr virus (EBV), including a positive Epstein-Barr virus (EBV) immunoglobulin M (IgM). (Viral load does not have to be positive) 23. Serologic evidence of acute infection with cytomegalovirus (CMV), defined as a positive cytomegalovirus (CMV) immunoglobulin G (IgG) and a positive viral load 24. Decreased lymphocytes (< 1000 lymphocytes/µL) 25. Decreased neutrophils (< 1000 PMN/µL on 2 consecutive evaluations performed on different days) 26. Decreased platelet count (< 150,000 platelets/µL) 27. Decreased hemoglobin (Hgb < 10 grams/deciliter [g/dL]) 28. Investigative site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child or s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess relative to placebo, the efficacy of teplizumab when administered according to 3 different teplizumab dosing regimens in subjects with recent-onset Type 1 Diabetes Mellitus (within 12 weeks of presentation of first signs and symptoms of disease to a physician). All regimens will be administered in addition to standard of care.;Secondary Objective: The secondary objectives of this study are to assess the durability of clinical benefit, the impact of teplizumab on health-related quality of life, and the safety and tolerability of teplizumab.;Primary end point(s): 1. To determine the difference in the proportion of subjects who have both a total daily insulin dose < 0.5 Units (U)/kilogram (Kg)/day and hemoglobin A1c (HbA1c) level < 6.5% between teplizumab and placebo 52 weeks after randomization 2. To determine the difference in mean HbA1c between teplizumab and placebo at 52 weeks after randomization For each endpoint, groups receiving different teplizumab treatment regimens will be compared independently to the placebo group with an adjustment made for multiplicity of statistical comparisons. The primary endpoints will be tested in the sequence in which they are listed, and the first endpoint must meet the required level of statistical significance in order for the second endpoint to be tested. Inclusion of the second primary endpoint ensures that a benefit of glycemic control results from teplizumab treatment and that meeting the first endpoint is not preferentially explained by lower insulin requirements in the teplizumab group. There will be no adjustment for multiplicity based on the two co-primary endpoints. | — |
Countries
Belgium, Czech Republic, Finland, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom
Outcome results
None listed