E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of Low Molecular Weight Dextran Sulfate (LMW-DS) to enhance engraftment and prevent IBMIR in islet transplantation to Type 1 diabetic subjects. |
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E.2.2 | Secondary objectives of the trial |
To gather additional safety and efficacy information about the combination of Low Molecular Weight Sulfated Dextran with islet transplantation. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Avbildning av ö-transplantation med PET och MR-teknik. Study protocol 2006-05-02. |
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E.3 | Principal inclusion criteria |
1. Patients between 18 to 65 years of age. 2 Subjects who are able to provide written informed consent and comply with the procedures of the study protocol. 3. Clinical history compatible with type 1 diabetes with onset of disease at <40 years of age and insulin-dependence for ≥5 years at the time of enrollment, and a sum of patient age and insulin dependent diabetes duration of >28. 4. Absent stimulated c-peptide <0.3 ng/ml [≤0.099 nmol/L] in response to a mixed meal tolerance test (MMTT; Boost® 6 mL/kg body weight to a maximum of 360 mL; another product with equivalent caloric and nutrient content may be substituted for Boost®) measured at 60 and 90min after the start of consumption. 5. Involvement in intensive diabetes management defined as self monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocinologist, diabetologist, or a diabetes specialist with at least 3 clinical evaluations during the previous 12 months prior to enrollment. 6. At least one episode of severe hypoglycemia, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; loss of consiousness; or visual symptoms; in which the subject was unable to treat him/herself and which was associated with either a blood glucose level <54 mg/dL [≤3.0 mmol/L] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, in the 12 months prior to study enrollment. 7. At least one of following: a. Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more or a HYPO score greater than or equal to the 90th percentile (1047) during the screening period and within the last 12 months prior to randomization; b. Marked glycemic lability characterized by wide swings in blood glucose despite optimal diabetes therapy and defined by a glycemic lability index (LI) score greater than or equal to the 90th percentile (433 mmol/L^2/hr*wk^-1) during the screening period and within the last 6 months prior to randomization; c. A composite of a Clarke score of 3 or more or a HYPO score greater than or equal to the 75th percentile (423) in combination with a LI greater than or equal to the 75th percentile (329) during the screening period and within the last 12 months prior to randomization.
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E.4 | Principal exclusion criteria |
1. Known IgE mediated allergy to antibiotics and antifungal medications (ciprofloxacin,gentamycin amfoteracin B) used in the culture medium. 2. Known hypersensitivity to dextran. 3. Body mass index (BMI) >30kg/m^2. 4. Insulin requirement of >1.0 IU/kg/day. 5. HbA1c >10%. 6. Untreated proliferative diabetic retinopathy. 7. Blood Pressure SBP >160 mmHg or DBP >100 mmHg. 8. Measured glomerular filtration rate (GFR) using 51Cr-EDTA, 99technetium-DPTA, or iohexol <80 ml/min/1.73 m^2. The absolute (raw) GFR value will be used for subjects with body surface areas>1.73^2 9. Presence or history of macroalbuminuria (>300mg /g creatinine). 10. Presence or history of panel-reactive anti-HLA antibodies >80% by flow cytometry. * 11. For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable. 12. Active infection including hepatitis B, hepatitis C or HIV. 13. Negative screen for Epstein-Barr Virus (EBV) by IgG determination. 14. Any history of malignancy. * 15. Known active alcohol or substance abuse. 16. Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/µL), neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL). Participants with lymphopenia are allowed if the investigator determines there is no additional risk and obtains clearance from a hematologist. 17. Homozygotic Activated Protein C Resistance (APC-R). 18. History of hypercoagulability disorder or coagulopathy or international normalization ratio (INR) >1.5. 19. Known history of severe co-existing cardiac disease. * 20. Consistently abnormal liver function tests at the time of study entry.* 21. Acute or chronic pancreatitis. 22. Patients with active peptic ulcer disease, symptomatic gallstones, or a history of portal hypertension. 23. Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications. 24. Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤5mg prednisone daily, or an equivalent dose of hydrocortisone, only for physiological replacement. 25. Treatment with any anti-diabetic medication, other than insulin, within 4 weeks of enrollment. 26. Use of any investigational agents within 4 weeks of enrollment. 27. Administration of live attenuated vaccine(s) within 2 months of enrollment. 28. Patients with any condition or any circumstances that in the opinion of the investigator would make it unsafe to undergo an islet transplant. 29. Treatment with any immunosuppressive regimen at the time of enrollment. 30. A previous islet transplant. 31. A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and the transplant occurred more than 6 months prior to enrollment.
* Please refer to study protocol for further details.
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E.5 End points |
E.5.1 | Primary end point(s) |
The level of stimulated c-peptide at 90 minutes derived from the mixed-meal tolerance test (MMTT) at 75±5 days following the first islet infusion.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |