A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate Efficacy and Safety of Teplizumab (MGA031), a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Children and Adults with Recent-Onset Type 1 Diabetes Mellitus - Protégé Encore
- Conditions
- Recent-onset type 1 diabetes mellitusMedDRA version: 9.1Level: LLTClassification code 10045228Term: Type I diabetes mellitus
- Registration Number
- EUCTR2009-011606-41-NL
- Lead Sponsor
- MacroGenics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
Subjects must meet all of the following criteria:
1. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria.
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 = 36 Kg
9. BSA =2.4 m2 (Interactive Voice Response System [IVRS] will be used to calculate BSA using the Mosteller formula )
10. Sexually active females, unless surgically sterile, must be willing to use 2 forms of contraception through the end of the study (Study Day 728). Acceptable forms of contraception for female subjects include: oral, transdermal, injectable or implanted contraceptives, intrauterine device (IUD), female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner, or sterile sexual partner. Abstinence is an acceptable form of contraception only if it is the subject’s pre-existing method of contraception. Male subjects with partners of child-bearing potential should use barrier contraception in addition to having their partners use another method of contraception
11. Willing to forego other forms of experimental treatment during the study
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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
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 (= 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 sibling, whether biologi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method