Durable-Response Therapy Evaluation For Early- or New-Onset Type 1 Diabetes - DEFEND 2
- Conditions
- Type 1 Diabetes MellitusMedDRA version: 12.1Level: LLTClassification code 10012608Term: Diabetes mellitus insulin-dependent
- Registration Number
- EUCTR2010-018775-17-IT
- Lead Sponsor
- Tolerx, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 396
1. No condition that, in the investigator’s judgment, is likely to cause the subject to be unable to understand the information in the assent form or Informed Consent Document (ICD) or provide informed consent. Such conditions would include, but are not limited to, psychoses or mental retardation with an IQ below 65. 2. Informed Consent Document signed by the subject if the subject is legally an adult. If the subject is legally a minor, ICD signed by the subject’s parent, both parents, or guardian and assent form signed by the subject, in accordance with the regulatory and legal requirements of the participating country. 3. Male or female, aged 12 to 45 years, inclusive, at the time of anticipated first dose of study drug. In Sweden, and Denmark, subjects must be aged 18 to 45 years. Subjects aged 12 to 17 years must be Tanner Stage >= 2. All subjects must weigh at least 31 kg. 4. a. Diagnosis of diabetes mellitus according to ADA criteria (Appendix 1), with an interval of = 90 days between the initial diagnosis and the first dose of study drug. Documentation of the diagnosis of DM, including the date of diagnosis, must be obtained from the diagnosing physician. b. History and clinical course consistent with type 1a (autoimmune) DM. 5. Currently requires insulin for T1DM treatment, or has required insulin for DM at some time between the date of diagnosis and the first dose of study drug. 6. Willing to undergo intensive insulin therapy and to self-monitor blood glucose levels at least 4 times daily from Screening through Month 24. 7. Willing to undergo continuous glucose monitoring for 6 day periods preceding the visits at Baseline and Months 6, 12, 18, and 24. 8. Willing to record all insulin taken over 7 consecutive days during the 2 weeks before each key visit and to report this information using IVRS/IWRS. Also willing to record hypoglycemic events throughout the 2 years of the study. 9. Willing to remain at the study center on each day of dosing until all assessments are complete, or longer if deemed medically necessary by the investigator. Willing to remain at the study center to undergo the MMTT at intervals of 3-12 months. 10. Positive for one or more of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti GAD); antibody to protein tyrosine phosphatase-like protein (anti IA 2); zinc transporter autoantibodies; insulin autoantibodies (IAA). A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has used insulin for a total of 7 days or more. 11. Evidence of residual functioning ß cells as measured by a stimulated C-peptide level over 0.20 nmol/L (0.6 µg/L) during an MMTT that was initiated when blood glucose level was > 70 mg/dL and = 200 mg/dL 12. Maximum stimulated C-peptide level = 3.50 nmol/L. 13. Body Mass Index (BMI) < 32
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
;
1. No condition that, in the investigator’s judgment, is likely to cause the subject to be unable to understand the information in the assent form or Informed Consent Document (ICD) or provide informed consent. Such conditions would include, but are not limited to, psychoses or mental retardation with an IQ below 65. 2. Informed Consent Document signed by the subject if the subject is legally an adult. If the subject is legally a minor, ICD signed by the subject’s parent, both parents, or guardian and assent form signed by the subject, in accordance with the regulatory and legal requirements of the participating country. 3. Male or female, aged 12 to 45 years, inclusive, at the time of anticipated first dose of study drug. In Sweden, and Denmark, subjects must be aged 18 to 45 years. Subjects aged 12 to 17 years must be Tanner Stage >= 2. All subjects must weigh at least 31 kg. 4. a. Diagnosis of diabetes mellitus according to ADA criteria (Appendix 1), with an interval of = 90 days between the initial diagnosis and the first dose of study drug. Documentation of the diagnosis of DM, including the date of diagnosis, must be obtained from the diagnosing physician. b. History and clinical course consistent with type 1a (autoimmune) DM. 5. Currently requires insulin for T1DM treatment, or has required insulin for DM at some time between the date of diagnosis and the first dose of study drug. 6. Willing to undergo intensive insulin therapy and to self-monitor blood glucose levels at least 4 times daily from Screening through Month 24. 7. Willing to undergo continuous glucose monitoring for 6 day periods preceding the visits at Baseline and Months 6, 12, 18, and 24. 8. Willing to record all insulin taken over 7 consecutive days during the 2 weeks before each key visit and to report this information using IVRS/IWRS. Also willing to record hypoglycemic events throughout the 2 years of the study. 9. Willing to remain at the study center on each day of dosing until all assessments are complete, or longer if deemed medically necessary by the investigator. Willing to remain at the study center to undergo the MMTT at intervals of 3-12 months. 10. Positive for one or more of the following autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti GAD); antibody to protein tyrosine phosphatase-like protein (anti IA 2); zinc transporter autoantibodies; insulin autoantibodies (IAA). A subject who is positive for IAA and negative for the other autoantibodies will not be eligible if the subject has used insulin for a total of 7 days or more. 11. Evidence of residual functioning ß cells as measured by a stimulated C-peptide level over 0.20 nmol/L (0.6 µg/L) during an MMTT that was initiated when blood glucose level was > 70 mg/dL and = 200 mg/dL 12. Maximum stimulated C-peptide level = 3.50 nmol/L. 13. Body Mass Index (BMI) < 32
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.If of childbearing potential (defined as women who are premenopausal [have had at least 1 menstrual period during the past 1 year] and have not had a hysterectomy or tubal ligation) must use adequate contraception if sexually active. 2. Significant systemic infection during the 6 weeks before the first dose of study drug. 3. 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). 4. A positive intradermal skin test for tuberculosis using purified protein derivative (PPD). 5. 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. 6. Clinically significant abnormal laboratory values during the Screening period, other than those due to T1DM. 7. Positive results for Hepatitis B surface antigen and for antibodies to Hepatitis B core antigen, and Hepatitis C. 8. Positive results for antibodies to HIV I and II, and considered by the investigator to be at high risk for HIV infection. 9. EBV viral load of > 10,000 copies per 10.000.000 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR). 10. A positive result on the Rapid Plasma Reagin (RPR) test for syphilis. 11. Have used any investigational drug within the 3 months before the first dose of study drug, and planning to take any investigational drug for the planned duration of study participation (2 years after the last dose of study drug). 12. Have used any 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, and expected 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.) 13. Have received a vaccine within the 30 days before the first dose of study drug, and expected to require a vaccine during the dosing period or the 14 days after the last dose of study drug. 14. Have previously received otelixizumab or any other anti-CD3 monoclonal antibody, e.g., OKT3 (muromonab or Orthoclone), ChAglyCD3, or hOKT3?1 (teplizumab, also known as 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). 15. Have previously received any anti-lymphocyte monoclonal antibody, such as anti-CD20, anti-thymocyte globulin (ATG), rituximab (Rituxan), or alemtuzumab (Campath), and planning to use any such antibody for the planned duration of study participation (2 years after the last dose of study drug). 16. Prior allergic reaction, including anaphylaxis, to any human, humanized, chimeric, or rodent antibody. 17. Condition or situation that, in the investigator’s judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments. 18. No prior allergic reaction, including anaphylaxis, to any component of the study drug product, e.g., histidine, disodium edetate, or polysorbate 80
;
1.If of childbearing potential (defined as women who are premenopausal [have had at least 1 menstrual period during the past 1 year] and have not had a hysterectomy or tubal ligation) must use adequate contraception if sexually active. 2. Significant systemic infection during the 6 weeks before the first dose of study drug. 3. 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). 4. A positive intradermal skin test for tuberculosis using purified protein derivative (PPD). 5. 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. 6. Clinically significant abnormal laboratory values during the Screening period, other than those due to T1DM. 7. Positive results for Hepatitis B surface antigen and for antibodies to Hepatitis B core antigen, and Hepatitis C. 8. Positive results for antibodies to HIV I and II, and considered by the investigator to be at high risk for HIV infection. 9. EBV viral load of > 10,000 copies per 10.000.000 peripheral blood mononuclear cells (PBMCs) as determined by quantitative polymerase chain reaction (qPCR). 10. A positive result on the Rapid Plasma Reagin (RPR) test for syphilis. 11. Have used any investigational drug within the 3 months before the first dose of study drug, and planning to take any investigational drug for the planned duration of study participation (2 years after the last dose of study drug). 12. Have used any 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, and expected 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.) 13. Have received a vaccine within the 30 days before the first dose of study drug, and expected to require a vaccine during the dosing period or the 14 days after the last dose of study drug. 14. Have previously received otelixizumab or any other anti-CD3 monoclonal antibody, e.g., OKT3 (muromonab or Orthoclone), ChAglyCD3, or hOKT3?1 (teplizumab, also known as 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). 15. Have previously received any anti-lymphocyte monoclonal antibody, such as anti-CD20, anti-thymocyte globulin (ATG), rituximab (Rituxan), or alemtuzumab (Campath), and planning to use any such antibody for the planned duration of study participation (2 years after the last dose of study drug). 16. Prior allergic reaction, including anaphylaxis, to any human, humanized, chimeric, or rodent antibody. 17. Condition or situation that, in the investigator’s judgment, is likely to cause the subject to be unable or unwilling to participate in study procedures or to complete all scheduled assessments. 18. No prior allergic reaction, including anaphylaxis, to any component of the study drug product, e.g., histidine, disodium edetate, or polysorbate 80
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method