Inducing Remission in Type 1 Diabetes With Alefacept
Condition: New-onset Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Alefacept; Placebo
Intervention description: Weekly intramuscular injections of alefacept (15 mg) for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.; Weekly intramuscular injections of a placebo saline solution of equal volume to the alefacept group for 2 cycles of 12 weeks each, separated by a 12 week pause in treatment.
Intervention MeSH terms: Alefacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 49.0
Sex: All
Minimum age: 12 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: New-onset Type 1 Diabetes Mellitus; New-onset T1DM; New-onset T1D; Alefacept; Amevive®

Summary:

      The purpose of this trial is to test whether a drug called alefacept will slow or halt
      destruction of the beta cells in the pancreas. If the destruction of the beta cells is
      stopped, the patients might be able to produce insulin on their own longer, which could stop
      or slow the progression of their type 1 diabetes.

      This is a multi-center prospective, placebo-controlled, double-blind and randomized trial to
      investigate the ability of alefacept to protect residual beta cells from ongoing autoimmune
      destruction in adolescents and young adults with newly diagnosed Type 1 Diabetes Mellitus
      (T1DM).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Recent diagnosis (within 100 days of enrollment) of T1DM

          -  Positive for at least one diabetes autoantibody (Glutamate decarboxylase
             [GAD-65GAD65], IA2, ZnT8, ICA and Insulin, if obtained within 10 days of the onset of
             exogenous insulin therapy)

          -  Peak stimulated C-peptide level > 0.2 pmol/mL following a mixed-meal tolerance test
             (MMTT)

          -  Willingness to provide written informed consent (either the subject or the subject's
             legally authorized representative).

        Exclusion Criteria:

          -  Severe reaction or anaphylaxis to human monoclonal antibodies

          -  History of malignancy or significant cardiovascular disease (including history of
             myocardial infarction, angina, use of anti-anginal medicines (e.g., nitroglycerin), or
             abnormal stress test)

          -  History of recent or ongoing uncontrolled bacterial, viral, fungal, or other
             opportunistic infections

          -  Evidence of infection with hepatitis B virus (HBV) as defined by hepatitis B surface
             antigen, HBsAg; hepatitis C virus (HCV) defined by anti-HCV antibodies; human
             immunodeficiency virus (HIV); or toxoplasmosis

          -  Positive tuberculin skin test (PPD)

          -  Clinically active infection with Epstein-Barr virus (EBV)-EBV viral load ≥ 10,000
             copies per 10^6 PBMCs; cytomegalovirus (CMV) -CMV viral load ≥10,000 copies per mL
             whole blood; or tuberculosis (TB)

          -  Diagnosis of liver disease or hepatic enzymes, as defined by ALT and/or AST ≥ 2 times
             the upper limit of normal

          -  Prior or current treatment that is known to cause a significant, ongoing change in the
             course of T1DM or immunologic status, including high-dose inhaled, extensive topical
             or systemic glucocorticoids

          -  Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides,
             thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin

          -  Current use of any medication known to influence glucose tolerance (e.g., atypical
             antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics,
             β-adrenergic blockers, niacin)

          -  Any of the following hematologic abnormalities, confirmed by repeat tests at least 1
             week apart:

               1. White blood count <4000/μL or >14,000/μL;

               2. CD4+ count below the lower limit of normal;

               3. Platelet count <150,000 /μL; or

               4. Hemoglobin <10 g/dL.

          -  Females who are pregnant, lactating, or planning on pregnancy during the 2-year study
             period

          -  History of bone marrow transplantation, or autoimmune disease associated with
             lymphopenia

          -  Any medical condition that in the opinion of the principal investigator would
             interfere with safe completion of the trial

          -  Prior participation in a clinical trial that could potentially affect T1DM or
             immunologic status

          -  Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated
             intranasal influenza vaccine, bacillus Calmette-Guérin, and smallpox) in the 6 weeks
             before enrollment

          -  Participation in an investigational clinical trial within the last six weeks.