Safety and Efficacy of PEG-Encapsulated Islet Allografts Implanted in Type I Diabetic Recipients

Novocell

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Diabetes Mellitus, Type 1

Treatments

Biological: Allogeneic Cultured Islet Cells (human); Encapsulated

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00260234

WIRB #20041068

NC-PCIA-04-001

Details and patient eligibility

About

Insulin dependent Type I diabetics require daily insulin therapy to normalize blood glucose but may have difficulty with significant glycemic excursions and hypoglycemic episodes and crises. Islet cell transplantation can provide relief from daily insulin therapy, normalize blood glucose and reduce or eliminate short and long-term diabetes-related complications. "PEG-Encapsulated Islet Allografts" is a new islet transplant product under development that does not require the ongoing use of immunosuppressive drugs after the implant. This study will test the safety and efficacy of PEG-Encapsulated Islet Allografts in the treatment of Type I diabetes and provide functional outcome measurements.

Full description

Allogeneic Cultured Islet Cells (human, Novocell); Encapsulated in Polyethylene Glycol; Administered Subcutaneously are a combination biologic and device product in which the pharmacologically active agent is human insulin that is released from the functional islet cells by natural production and release, stimulated by control mechanisms in response to blood glucose concentrations. The device component is a uniform and conformal polymer coating around each islet. Islet cells are isolated from multiple human pancreases procured from human organ donors who meet a specific human donor profile established by the UNOS and the FDA's requirements for Good Tissue Practices. Because the pancreases used for islet cell isolation are not intended for whole-organ transplantation, specific procurement, surgical removal, packaging and shipping protocols are provided by Novocell, Inc. to the Organ Procurement Organizations.

The primary outcome is demonstration that encapsulated islet allografts can be implanted safely in the subcutaneous tissues without the use of long-term immunosuppression. The expected functional outcomes from the implantation of the encapsulated islets are significant reductions in the average blood glucose daily glycemic excursions and in insulin requirements as well as significant increases in C-peptide levels in response to meal challenges. The ultimate expected outcome is that patients who receive these implants will have reduced hemoglobin A1c levels that may be associated with reduced long-term diabetic complications. An important outcome should be reduction in hypoglycemic episodes and crises with significantly functioning grafts without having the risks associated with hepatic portal vein infusion and long-term immunosuppression.

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or non-pregnant non-lactating female subjects > 20 years of age
Diagnosed with insulin-dependent type I diabetes for at least 20 years
BMI less than 28 kg/m2
Insulin requirement less than or equal to 0.7 U/kg/day
HbA1c greater than or equal to 7.0 %
Serum C-peptide concentration less than or equal to 0.5 ng/mL stimulated by an OGTT
Female subjects with childbearing potential must have a negative serum pregnancy test prior to enrollment and must agree to use an effective contraceptive method during the study
One year of stable diabetes care established in the PI's database without significant changes in insulin requirement or HbA1c or diabetic complication profile

Exclusion criteria

Diagnosis of type II diabetes or maturity onset diabetes of youth (MODY)
Serum C-peptide greater than 0.5 ng/mL stimulated by OGTT
Sustained hypertension greater than or equal to 100 mmHg diastolic and/or greater than or equal to 160 mmHg systolic
History of myocardial infarction or current active cardiac disease
Current active infection
Significant renal dysfunction as indicated by GFR less than 80 mL/min/1.73 m2 and/or urinary albumin greater than 500 µg/mL
Significant liver dysfunction as indicated by ALT or AST more than 3X the upper limit of normal
Prior whole organ or islet cell transplant
Concurrent immunosuppressive therapy
Severe gastroparesis, severe peripheral neuropathy, diabetic foot ulcers, or prior amputations due to diabetic complications
Any other active autoimmune disease other than autoimmune thyroid disease
HIV, HBV or HCV positive status
Uncontrolled or untreated proliferative retinopathy
Known hypersensitivity or other intolerance to cyclosporine or the inactive ingredients in the product
Behavioral activities that place the subject at risk in the opinion of the investigator
Any significant concurrent disease, illness, or psychiatric disorder that would, in the opinion of the investigator, compromise subject safety or compliance, or interfere with consent, study participation, follow-up, or the interpretation of study results
History of any kind of cancer other than skin cancers (except for melanoma which is exclusionary)