DEFEND-1: Durable Response Therapy Evaluation For Early Or New Onset Type 1 Diabetes - DEFEND-1

Conditions: Early or New Onset Type 1 Diabetes
MedDRA version: 9.1Level: LLTClassification code 10045228Term: Type I diabetes mellitus

Registration Number: EUCTR2008-002205-40-IT

Lead Sponsor: TOLERX,INC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1. No condition that,in the investigator`s judgement,is likely to cause the subject to be unable to understand the information in the Informed Consent Document (ICD) or provide informed consent. Such conditions would include,but are not limited to,psychoses or mental retardation with IQ below 65 2.Informed Consent Document signed by the subject 3.Male or female, aged 18 to 35 years,inclusive,at the time of anticipated first dose of study drug 4.Diagnosis of diabetes mellitus according to ADA and WHO criteria (Appendix 2) and consistent with type 1a (autoimmune) DM,with interval of 90 days or less between the initial diagnosis and first dose of study drug.Written documentation of the diagnosis of DM,including the date of diagnosis,must be obtained from the diagnosing physician 5. Currently requires insulin treatment for T1DM.The subject may use long-acting,intermediate-acting,regular,and/or very short-acting insulin.Use of an insulin pump is permitted but not required;use of inhaled insulin is prohibited 6. Willing to undergo intensive insulin therapy and to self-monitor blood glucose level at least 4 times daily from screening through Month 24 and 7 times daily over 7 consecutive days during the 2 weeks before each study visit 7. Willing to record home insulin use,blood glucose levels,and signs and symptoms of hypoglycemic excursions using an electronic personal device assistant,complying with all data transmission requirements,for the planned duration of study participation (2 years after the last dose of study drug) 8.Willing to remain at the study center for at least 6 hours on each day of dosing,i.e.,on 8 consecutive days,and to undergo the mixed meal tolerance test (MMTT) at intervals of 3-12 months 9.positive for one or both of the following autoantibodies typically associated with T1DM:antibody to glutamic acid dexarboxylase (anti-GAD) or antibody to protein tyrosine phosphatase-like protein (anti-IA-2) 10. Evidence of residual functioning beta cells as measured by a stimulated C-peptide level >0,20 nmol/L during the Screening or Predose MMTT when glucose blood level is >70 mg/dL and equal or less to 200 mg/dL 11. Maximum stimulated C-peptide level equal or less then 3.50 nmol/L 12 Body Mass Index (BMI)< 32.
Are the trial subjects under 18? no
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant, breastfeeding,or planning to become pregnant during the 60 days after the last dose of study drug 2.If of childbearing potential (defined as woman who are premenopausal -have had at least 1 menstrual period during the last past year-and have not had a hysterectomy or tubal ligation),not using adequate contraception if sexually active 3.Significant systemic infection during the 6 weeks before the first dose of study drug 4. Current or prior malignancy,other than non-melanoma skin cancer (subject must have fewer than 5 occurrences of non-melanoma skin cancer,and the last occurrence must not be within 3 months of study entry) 5.A positive intradermal skin test for tuberculosis using purified protein derivative (PPD) 6.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 7.Clinically significant abnormal laboratory values during the screening period,other than those due to T1DM 8.Positive results for Hepatitis B surface antigen and for antibodies to Hepatitis B core antigen, and Hepatitis C 9.Positive results for antibodies to HIV I and II,and considered by the investigator to be at high risk for HIV infection 10. EBV viral load of >10,000 copies per 106 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR) 11. A positive result on the Rapid Plasma Reagin (RPR test) for syphilis;or,if result of RPR test is positive, a negative confirmatory test (for example,fluorescent treponemal antibody absorbed test-FTA-ABS) 12. Have used any investigational drug within the 3 months before signing the ICD,and planning to take any investigational drug for the planned duration of the study participation (2 years after the last dose of study drug) 13.Have used any potent immunosuppressive agent (e.g. systemic high-dose corticosteroids on a chronic basis,methothrexate,cyclosporine,or anti-TNF agents)within the 30 days before signing the ICD,and expected to require such a treatment within 3 months after the last dose of study drug ( intranasal,inhaled,and topical corticosteroid medications are permitted if used at reccomended dosages) 14.Have received a vaccine within the 30 days before signing the ICD,and expected to require a vaccine during the dosing period of the 14 days after the last dose of the study drug 15. Have previously received otelixizumab or any other anti-CD3 monoclonal antibody,e.g. OKT3 (muromonab or Orthoclone),ChAglyCD3,or hOKT3gama1 (ala-ala),and not willing to refrain from using any such antibody for the planned duration of study participation (2 years after the last dose of study drug) 16.Have previously received any anti-lymphocyte monoclonal antibody,such as anti-CD20,anti-thymocite globulin(ATG),rituximab (Rituxan),or alemtuzumab (Campath), and not planning to use any such antibody for the planned duration of study partecipation (2 years after the last dose of study drug) 17. Prior allergic reaction,including anaphylaxis,to any human,humanized,chimeric,or rodent antibody 18. Condition or situation that, in investigator`s judgement,is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments