LEA29Y (Belatacept) Emory Edmonton Protocol

NCT00468403 | Completed Phase 2 DMC

• 1 other identifier: DAIT CIT-04
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

Brief Summary

Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation using a steroid-free, calcineurin-inhibitor-free belatacept based immunosuppressive medication, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

Conditions

Type 1 Diabetes Mellitus

Keywords

Insulin dependence; Hypoglycemia; Hypoglycemia unawareness

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with insulin independence

  75 days after first islet transplant

Secondary Outcomes (29)

• Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events

  from Day 28 to Day 365, inclusive, after the first islet transplant

• Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events

  from Day 28 to Day 365, inclusive, after the final islet transplant

• Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score

  75 Days after first and final islet transplant

• Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ration, acute insulin response to glucose

  75 Days after first and final islet transplant

• Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test

  75 days after first and final islet transplant

Study Arms (1)

Allogeneic Pancreatic Islet Cells

EXPERIMENTAL

Participants will receive up to three islet transplantations and continuous immunosuppressive therapy including belatacept

Biological: Allogeneic Pancreatic Islet Cells; Biological: Belatacept; Biological: Basiliximab; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Procedure: Intraportal infusion of islet cells

Interventions

Allogeneic Pancreatic Islet Cells BIOLOGICAL

Transplant of islet cells from a healthy pancreas. A dose of at least 5,000 Islet Equivalents (IEQ)/kg recipient body weight (BW) infused intraportally for the first transplant, and at least 4,000 IEQ/kg recipient BW infused intraportally for subsequent transplants.

Allogeneic Pancreatic Islet Cells

Belatacept BIOLOGICAL

Belatacept is an inhibitor of the 2 signals that stimulate T-cells. Subjects will receive NULOJIX® (belatacept)10mg/kg through a peripheral vein on Day 0 and post-operative days 4, 14, 28, 56, 84. After Day 84 subjects will receive belatacept at a maintenance dose of 5 mg/kg every 4 weeks for the duration of study follow-up (2 years after the final islet transplant). Infusion doses will be based upon the subject's actual body weight at study Day 0 and will not be modified during the course of the study unless there is a change in body weight plus or minus 10% of Day 0 body weight.

Also known as: NUJOLIX

Allogeneic Pancreatic Islet Cells

Basiliximab BIOLOGICAL

Immunosuppressive medication for prophylaxis of acute transplant rejection. Two Intravenous (IV) doses of basiliximab, a monoclonal antibody Interleukin 2 (IL-2) receptor blocker, will be given with the first and second (if necessary) transplants. The first dose will be 20 mg and will be given within two hours prior to islet transplant on the day of islet transplantation. The second 20 mg dose will be given on Day 4 after the transplant.If a third islet transplant is deemed necessary and performed more than 70 days after the second transplant, both doses of basiliximab will be repeated. No additional doses of basiliximab will be given with a third transplant that is performed between 30 and 70 days after the second transplant.

Also known as: Simulect

Allogeneic Pancreatic Islet Cells

Mycophenolate Mofetil DRUG

Maintenance immunosuppressive therapy. Subjects will receive mycophenolate mofetil starting immediately pre-transplant on Day 0 at a dose of 1g orally twice a day for the duration of study follow-up (2 years after the final islet transplant).

Also known as: Cellcept

Allogeneic Pancreatic Islet Cells

Tacrolimus DRUG

Tacrolimus may be used only as a supplement to maintenance mycophenolate mofetil (MMF) in those cases where the trough level is below the therapeutic range. Tacrolimus will be administered orally twice a day to maintain trough levels of 3-5 ng/mL. Generic equivalents of Prograf® will not be permitted.

Also known as: Prograf

Allogeneic Pancreatic Islet Cells

Intraportal infusion of islet cells PROCEDURE

The infusion of allogeneic pancreatic islet cells (islet transplant\[s\]) will occur intraportally.

Allogeneic Pancreatic Islet Cells

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mentally stable and able to comply with study procedures
• Clinical history compatible with type 1 diabetes with onset of disease at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test
• Involvement of intensive diabetes management, defined as:
• Self-monitoring of glucose no less than a mean of three times each day averaged over each week
• Three or more insulin injections each day or insulin pump therapy
• Under the care of an endocrinologist, diabetologist, or diabetes specialist with at least three clinical evaluations during the past 12 months prior to study enrollment
• 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; seizure; loss of consciousness; or visual symptoms, in which the participant was unable to treat him/herself and which was associated with either a blood glucose level less than 54 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagons in the 12 months prior to study enrollment
• Reduced awareness of hypoglycemia. More information about this criterion is in the protocol.

You may not qualify if:

• Body mass index (BMI) greater than 30 kg/m\^2 or weight less than or equal to 50 kg (110 lbs)
• Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
• HbA1c greater than 10%
• Untreated proliferative diabetic retinopathy
• Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
• Measured glomerular filtration rate using iohexol of less than 80 mL/min/1.73m\^2.
• Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
• Presence or history of panel-reactive anti-Histocompatibility Antigen (HLA) antibody levels greater than background by flow cytometry. More information about this criterion is in the protocol.
• Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
• All women more than 35 years and women of any age who have first degree relatives with a history of breast carcinoma or who have other risk factors of breast carcinoma. More information about this criterion is in the study protocol.
• Active infection, including hepatitis B, hepatitis C, human immunodeficiency virus (HIV). Presence or history of tuberculosis. More information about these criteria is in the protocol.
• Negative for Epstein-Barr virus (EBV) by anti-viral capsid antigen (VCA) IgG (EBV VCA-IgG) determination
• Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection in the past year
• History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• Known active alcohol or substance abuse

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Clinical Islet Transplantation Consortium: collaborator

Study Sites (2)

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Alberta

Edmonton, Alberta, T6G028, Canada

Location

Related Publications (1)

• Gala-Lopez B, Kin T, O'Gorman D, Pepper AR, Senior P, Humar A, Shapiro AM. Microbial contamination of clinical islet transplant preparations is associated with very low risk of infection. Diabetes Technol Ther. 2013 Apr;15(4):323-7. doi: 10.1089/dia.2012.0297. Epub 2013 Feb 25.

  PMID: 23438305 DERIVED

Related Links

• Click here for the Clinical Islet Transplantation Consortium Web site
• National Institute of Allergy and Infectious Diseases

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

Abatacept; Basiliximab; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunoproteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• A.M. James Shapiro, MD, PhD

  Clinical Islet Transplant Program, University of Alberta

  STUDY CHAIR

• Nicole Turgeon, MD

  Clinical Islet Transplant Program, Emory University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2007
• First Posted: May 2, 2007
• Study Start: October 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2013
• Last Updated: April 7, 2016

Record last verified: 2016-03

Locations

US (1); CA (1)