Islet Transplantation Using Abatacept

NCT00276250 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB000218521136-2005
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation in type 1 diabetics with hypoglycemic unawareness using abatacept as a part of a novel calcineurin-inhibitor-sparing immunosuppressive regimen.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• The Number of Insulin-independent Subjects at Day 75 (± 5 Days) Following the First Islet Cell Transplantation

  75 days post-transplantation

Secondary Outcomes (8)

• Number of Insulin-independent Subjects Following Islet Transplantation

  1, 3, 6, 9,12,18 and 24 months post-transplantation

• Number of Subjects With HbA1C Less Than 6.5%

  6 months post-transplantation

• Number of Subjects With HbA1C Levels < 6.5%

  12 months post-transplantation

• Number of Subjects With HbA1C < 6.5%

  24 months post-transplant

• Number of Subjects With HbA1C < 6.5%

  36 months post-transplantation

Study Arms (3)

Efalizumab Followed by Abatacept Regimen

EXPERIMENTAL

Participants with Type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependence for \> 5 years received efalizumab-based immunosuppression regimen after islet-cell transplantation. During the course of the study, efalizumab was withdrawn from the US market due to safety concerns. The protocol was subsequently amended to alter the immunosuppressive regimen to abatacept for these participants.

Drug: Efalizumab; Drug: Abatacept

Abatacept Regimen

EXPERIMENTAL

Participants with Type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependence for \> 5 years received abatacept immunosuppresion regimen after islet-cell transplantation.

Drug: Abatacept

Belatacept Regimen

EXPERIMENTAL

Participants with Type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependence for \> 5 years received Belatacept immunosuppresion regimen after islet-cell transplantation.

Drug: Belatacept

Interventions

Efalizumab DRUG

Efalizumab was a medication approved for use in psoriasis which was being explored to determine efficacy with immunosuppression following organ transplantation. Efalizumab was administered subcutaneously on a weekly basis. Upon efalizumab being withdrawn from the US market, the protocol was amended to alter the immunosuppressive regimen to abatacept for the study participants.

Also known as: Raptiva

Efalizumab Followed by Abatacept Regimen

Abatacept DRUG

Abatacept is drug used to treat autoimmune diseases. Abatacept is administered intravenously, monthly, in weight-based doses and is given for as long as transplanted islets are functioning.

Also known as: Orencia

Abatacept Regimen; Efalizumab Followed by Abatacept Regimen

Belatacept DRUG

Belatacept is a medication to provide extended graft survival while limiting the toxicity generated by standard immune suppressing regimens. Belatacept is administered intravenously. The protocol for this study was amended to substitute belatacept for abatacept for all newly enrolling participants (current participants remained on abatacept).

Also known as: Nulojix

Belatacept Regimen

Eligibility Criteria

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

You may qualify if:

• Male and Female patients age 18 to 65 years of age
• 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.
• Body mass index less than or equal to 26
• to 65 years of age
• Absent stimulated C-peptide (\<0.3ng/ml) in response to a mixed meal tolerance test (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 90min after the end of consumption.
• Compliance with an optimized diabetic management plan as assessed by an Emory University endocrinologist
• Checking and recording blood sugars at least 3 times per day
• 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 endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the previous 12 months.
• At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person and which was associated with either a blood glucose level \<50 mg/dL \[2.8 mmol/L\] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration).
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more and a HYPO score greater than or equal to the 90th percentile (1047) within the last 6 months prior to randomization; OR 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 mM2/h/wk) within the last 6 months prior to randomization; OR A composite of a Clarke score of 4 or more and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than of equal to the 75th percentile (329) within the last 6 months prior to randomization.

You may not qualify if:

• Severe co-existing cardiac disease, characterized by any one of these conditions:
• Recent myocardial infarction (within past six months)
• Left Ventricular Ejection Fraction \< 30%
• Evidence of ischemia on a functional echocardiogram
• Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a positive skin test or clinical presentation, or under treatment for suspected TB. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection. Positive tests are otherwise not acceptable, even in the absence of any active infection at the time of evaluation
• Invasive aspergillus infection within one year prior to study entry.
• Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
• Administration of live vaccine within the past two months
• Measured glomerular filtration rate using iohexol \<70 mL/min/1.73 m2 for females and \<80 mL/min/1.73 m2 for males (or a 24 hr. creatinine clearance with participants allergic to iodine \<85mL/min/1.73m2).
• Macroalbuminuria (urinary protein excretion rate \>300 mg/24h)
• Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia (\<1,000/L), neutropenia (\<1,500/L), or thrombocytopenia (platelets \<100,000/ L).
• Hyperlipidemia (fasting LDL cholesterol \>130 mg/dL, treated or untreated; and/or fasting triglycerides \>300 mg/dL)
• Negative antibody test for Varicella zoster virus (subjects may be reconsidered if they receive the vaccination and convert to a positive antibody)
• History of malignancy (except squamous or basal cell skin carcinoma) within the previous 5 years
• Previous/concurrent organ transplantation

Sponsors & Collaborators

• Emory University: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

efalizumab; Abatacept

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

Limitations and Caveats

Enrollment in this study was limited by the removal of Efalizumab from the market in 2009 after patients (external to this study) being treated for plaque psoriasis were diagnosed with Progressive Multifocal Leukoencephalopathy (PML).

Results Point of Contact

• Title: Nicole Turgeon, MD
• Organization: Emory University

nturgeo@emory.edu

404-727-3257

Study Officials

• Christian P Larsen, MD, D.Phil

  Emory University

  PRINCIPAL INVESTIGATOR

• Thomas C Pearson, MD, D,Phil

  Emory University

  PRINCIPAL INVESTIGATOR

• Sallie C Carpentier, RN, BSN

  Emory University

  STUDY DIRECTOR

• Nicole Turgeon, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 12, 2006
• First Posted: January 13, 2006
• Study Start: December 1, 2005
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 27, 2016
• Results First Posted: July 27, 2016

Record last verified: 2016-06

Locations

US (1)