Clinical Trial of Teplizumab (MGA031) in Children and Adults with Recent-Onset Type 1 Diabetes Mellitus

Phase 1

• Conditions: Recent-onset type 1 diabetes mellitus; MedDRA version: 14.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2009-011606-41-GB
• Lead Sponsor: MacroGenics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-08-17
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 400

Inclusion Criteria

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 at screening.
3. Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes.
4. Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug.
5. Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening.
6. Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening:
a. Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2),
b. Glutamic acid decarboxylase (GAD) autoantibodies, or
c. Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive).
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: 145
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 at Study Day 0.
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 systemic corticosteroids during the trial are also excluded.
14. Evidence of active infection.
15. History of or positive test for human immunodeficiency virus (HIV).
16. Positive immunoglobulin M (IgM) test for hepatitis A.
17. History of or positive test for hepatitis B, C, or D.
18. Total bilirubin > 1.5 x upper limit of normal (ULN).
19. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 x ULN.
20. Evidence of active or latent tuberculosis (TB), which may include a positive purified protein derivative (PPD) skin test result; 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.
21. Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 of the study.
• Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle.
• Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle.
22. Any infectious mononucleosis-like illness within the 6 months before randomization.
23. 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).
24. Serologic ev

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified