Clinical Trial of Teplizumab (MGA031) in Children and Adults with Recent-Onset Type 1 Diabetes Mellitus
- Conditions
- Recent-onset type 1 diabetes mellitusTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]MedDRA version: 14.1Level: LLTClassification code 10045228Term: Type I diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders
- Registration Number
- EUCTR2009-011606-41-DE
- Lead Sponsor
- MacroGenics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
Subjects must have met all of the following criteria:
- Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria.
- Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
- Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening
- 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)
- Subjects 8–35 years old; France only: Subjects 18–35 years old
- Body weight = 36 Kg
- BSA =2.4 m2 (Interactive Voice Response System [IVRS] will be used to calculate BSA using the Mosteller formula )
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 108
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects must not have had any of the following criteria:
- Prior administration of a monoclonal antibody—within the 1 year before randomization at Study Day 0
- Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
- Prior murine OKT®3 treatment or other anti-CD3 treatment
- 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
- Current treatment with oral antidiabetic agents
- Evidence of active infection
- History of or positive test for human immunodeficiency virus (HIV)
- History of or positive tests for hepatitis B, C or D
- 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
- Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 (Study Day 364) of the study:
a. Influenza vaccinations with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing course.
b. Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing course
- Any infectious mononucleosis-like illness within the 6 months before randomization
- 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)
- Serologic evidence of acute infection with cytomegalovirus (CMV), defined as a positive cytomegalovirus (CMV) immunoglobulin G (IgG) and a positive viral load
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: The secondary objectives of this study are to assess the durability of clinical benefit and the safety and tolerability of teplizumab. ;Primary end point(s): 1. 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% at Study Day 364 <br><br>2. The mean HbA1c change from baseline to Study Day 364 ;Timepoint(s) of evaluation of this end point: Primary endpoints are assessed according to the protocol;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 were administered in addition to standard of care.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary endpoints of the study are:<br>• The mean fasting C-peptide change from baseline to Study Day 364<br>• Incidence of total, major, minor and nocturnal hypoglycemia at Study Day 364<br>• Mean number of daily insulin injections received at Study Day 364;Timepoint(s) of evaluation of this end point: Secondary endpoints are assessed at multiple timepoints according to the protocol