Investigating Re-Dosing With Otelixizumab in Adults With Newly-Diagnosed Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: otelixizumab
Intervention description: Two treatment courses of otelixizumab given 6 months apart. Each treatment course will consist of 8 consecutive days of otelixizumab intravenous infusions (each given over 30 minutes).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: newly diagnosed type 1 diabetes mellitus; re-treatment; intravenous otelixizumab; beta-cell preservation

Summary:

      The purpose of this study to assess the safety and tolerability of re-dosing at 6 months with
      otelixizumab (given as an 8-day series of intravenous infusions) in adult subjects with newly
      diagnosed type 1 diabetes mellitus
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged 18 to 45 years. Women are allowed if they are of non-childbearing
             potential or agree to use one of the contraception methods listed in the protocol.

          -  Diagnosis of type 1 autoimmune diabetes mellitus according to ADA and WHO criteria

          -  No more than 90 days between diagnosis and the first dose of study drug.

          -  Currently requires insulin for T1DM treatment, or has required insulin at some time
             between diagnosis and the first dose of study drug.

          -  Positive for one or more of the autoantibodies typically associated with T1DM:
             antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine
             phosphatase-like protein (anti-IA-2); or insulin autoantibodies (IAA). A subject who
             is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies
             will only be eligible if the subject has used insulin for less than 7 days total.

          -  Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50
             nmol/L

          -  Body mass index not greater than 32 kg/m2.

          -  QTc <450 millisecond (msec) or <480msec for patients with Bundle Branch Block

        Exclusion Criteria:

          -  Pregnant, breastfeeding, or planning to become pregnant from the beginning of the
             screening period or at least 14 days prior to initial dosing until at least 60 days
             after the last dose of the second treatment course of study drug.

          -  Current or prior malignancy, other than non-melanoma skin cancer (subject must have
             had fewer than 5 occurrences of non-melanoma skin cancer, and the last occurrence must
             not be within 3 months of study entry).

          -  Clinically significant abnormal laboratory values during the Screening period, other
             than those due to T1DM. Permitted ranges for selected laboratory values are shown in
             the protocol. A clinically significant abnormal value will not result in exclusion if,
             upon re test, the abnormality is resolved or becomes clinically insignificant.

          -  Significant and/or active disease in any body system likely to increase the risk to
             the subject or interfere with the subject's participation in or completion of the
             study. Examples of significant diseases include, but are not limited to, coronary
             artery disease, congestive heart failure, uncontrolled hypertension, renal failure,
             emphysema, history of bleeding peptic ulcers, history of seizure(s), addiction to
             illicit drugs, and alcohol abuse.

          -  Current or chronic history of liver disease, known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of
             hepatitis B surface antigen (HBsAg), positive hepatitis C test result within 3 months
             of screening

          -  Significant systemic infection during the 6 weeks before the first dose of study drug
             (e.g., infection requiring hospitalisation, major surgery, or IV antibiotics to
             resolve; other infections, e.g., bronchitis, sinusitis, localised cellulitis,
             candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by
             the investigator regarding whether they are serious enough to warrant exclusion).

          -  History of current or past active tuberculosis infection and or latent tuberculosis
             infection. Further details are given in the protocol.

          -  A positive test for human immunodeficiency virus (HIV) antibody or risk factors which
             predispose subject to HIV infection.

          -  EBV viral load greater than or = to 10,000 copies per 10xe6 peripheral blood
             mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction
             (qPCR). If there is any clinical suspicion that a subject who is EBV seronegative and
             with EBV PCR <10,000 copies per 10xe6 PBMCs has symptoms consistent with infectious
             mononucleosis prior to administration of study drug, then a monospot test result must
             be negative before the subject can be dosed.

          -  A positive test for syphilis.

          -  Had a potent immunosuppressive agent (e.g., systemic high-dose corticosteroids on a
             chronic basis, methotrexate, cyclosporine, or anti-TNF agents) within the 30 days
             before the first dose of study drug, or expecting to require such treatment within 3
             months after the last dose of study drug. (Intranasal, inhaled, and topical
             corticosteroid medications are permitted if used at recommended dosages.)

          -  Used an atypical antipsychotic drug (e.g., risperidone [Risperdal], quetiapine
             [Seroquel], or clozapine [Clozaril]) within the 30 days before first dose of study
             drug, or expecting to require such treatment during the study.

          -  Received a vaccine within the 30 days before the first dose of study drug, or
             expecting to require a vaccine during the dosing period or the 30 days after the last
             dose of study drug.

          -  Previously received otelixizumab or any other anti CD3 monoclonal antibody, e.g., OKT3
             (muromonab or Orthoclone), ChAglyCD3, or hOKT3γ1 (ala ala), or not willing to refrain
             from using any such antibody for the planned duration of study participation (18
             months after the last dose of study drug).

          -  Previously received an anti lymphocyte monoclonal antibody, such as anti-CD20,
             anti-thymocyte globulin (ATG), rituximab (Rituxan), or alemtuzumab (Campath), or
             planning to use any such antibody during the planned duration of study participation
             (18 months after the last dose of study drug).

          -  Had an investigational drug within the 3 months before the first dose of study drug or
             planning to take an investigational drug within18 months of the last dose of study
             drug.

          -  Have donated any plasma or blood within 45 days before the first dose of study drug.

          -  Prior allergic reaction, including anaphylaxis, to any human, humanised, chimeric, or
             rodent antibody.

          -  Undergone a major surgical procedure within 30 days before the first dose of study
             drug, or planning to undergo any such surgery within 3 months after the last dose of
             study drug.