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Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

Phase 3
Completed
Conditions
Health Condition 1: null- Recent Onset Type 1 Diabetes Mellitus
Registration Number
CTRI/2009/091/000916
Lead Sponsor
MacroGenics Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
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, 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 formula1)

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

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 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. AST or 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 vaccinations 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

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Successful versus unsuccessful clinical responses. A successful response requires that both components of a composite endpoint are met. The composite endpoint includes both the subjects total daily insulin usage and his/her HbA1c levels.Timepoint: Not Applicable
Secondary Outcome Measures
NameTimeMethod
â?¢Successful versus unsuccessful clinical responses. A successful response requires that both components of a composite endpoint are met. The composite endpoint includes both the subjects total daily insulin usage and his/her HbA1c levels <br/ ><br> <br/ ><br>C-peptide secretory responses, as defined by the total area under the curve of the C-peptide response to a mixed meal <br/ ><br>Timepoint: Not Applicable
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