Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      Anti-CD3 monoclonal antibody (a.k.a. hOKT3gamma1 [Ala-Ala],teplizumab, MGA031) is a humanized
      antibody that is commonly used to prevent organ rejection. The purpose of this study is
      determine whether anti-CD3 mAb treatment can halt the progression of newly diagnosed type 1
      diabetes.
    

Detailed description: 
      Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks
      insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain
      proper blood glucose levels in response to daily activities, such as eating or exercise.
      Generally, at the time of type 1 diabetes diagnosis, 60% to 85% of the diabetic person's beta
      cells have already been destroyed. However, between 15% and 40% of these cells remain and are
      able to produce insulin. Treatment that slows the destruction of additional beta cells may be
      able to decrease a patient's reliance on insulin and improve their quality of life.

      Anti-CD3 mAb is genetically engineered and directed against the CD3 antigen on T cells; this
      antibody selectively attacks the immune cells responsible for beta cell destruction. In a
      small exploratory clinical trial, patients with newly diagnosed type 1 diabetes who received
      a single, 2-week treatment with anti-CD3 mAb had preserved beta cell function and
      significantly lower insulin requirements than untreated patients for up to two years after
      therapy. This study will investigate whether a second course of anti-CD3 mAb administered one
      year after the first administration is able to prolong or improve the effects of the biologic
      in people who have recently diagnosed type 1 diabetes mellitus.

      Participants will be randomly assigned to one of two groups. The Experimental Group will
      receive anti-CD3 mAb treatment plus Diabetes Standard of Care Treatment; the Active
      Comparator Group will receive Diabetes Standard of Care Treatment. The Experimental Group
      will be treated with the antibody for the first 14 days of the study and again one year
      later. These participants will be admitted to the hospital for the first 5 days of a
      treatment cycle. Participants who live within 1 hour of the hospital may receive the
      remainder of a treatment cycle as an outpatient, but those who live farther away will be
      hospitalized for 14 days. For the first treatment cycle, there will be study visits on the 3
      consecutive days after the treatment cycle and at Months 1, 2, 3, 6, 9, and 12. For the
      second treatment cycle, there will be study visits on the 3 consecutive days after the
      treatment cycle and at Months 13, 16, 19, 21, and 24.The Active Comparator Group will have 12
      study visits over two years.

      At study entry, all participants will receive daily iron supplementation, either as ferrous
      sulfate or a multivitamin with iron. Participants will be followed for up to 2 years to
      assess their overall diabetes health and to capture laboratory measures of beta cell and
      immune system function. Medication history and adverse event assessment will occur at all
      visits. A physical exam, vital signs measurement, and blood collection will occur at most
      visits. Medical history and urine collection will occur at selected visits.
    

Intervention name(s): Anti-CD3 mAb; Diabetes Standard of Care Treatment; Iron supplementation
Intervention type(s): Biological; Other; Dietary Supplement
Intervention description(s): Daily 14-day dose escalation course at study entry, with possible second course after 12-month interval; Receipt of intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.; Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.
Other intervention name(s): mAb hOKT3gamma1(Ala-Ala); teplizumab; MGA031; MVI; Fer-In-Sol; Feosol; Fer-Iron; Ferolix; FeroSul; Irospan
Intervention MeSH terms: Iron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: T1D; type 1 diabetes; type 1 diabetes mellitus; juvenile diabetes; autoimmune diabetes; autoimmune; anti-CD3 mAb; mAb hOKT3g1(Ala-Ala); teplizumab