Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes

NCT00672204 | Terminated Phase 1 Results DMC

• 1 other identifier: 0612M98726
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this protocol is to test the safety and efficacy of a treatment regimen consisting of maintenance therapy with efalizumab and sirolimus for 1 year followed by withdrawal of efalizumab and maintenance therapy with sirolimus, for the prevention of the destruction and rejection of islet transplants in type 1 diabetic recipients. Genentech, the manufacturer of efalizumab voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects have been transitioned to alternative immunosuppressives and no new subjects will be transplanted under this protocol.

Conditions

Type 1 Diabetes Mellitus; Hypoglycemia

Keywords

Islet transplant; Diabetes Mellitus; Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• The Proportion of Insulin-independent Subjects With Full Islet Graft Function

  Islet transplant recipients will be considered insulin-independent with full islet graft function if they are able to titrate off insulin therapy for at least 1 week and all of the following criteria are met: * HbA1c \< 7.0% or a ≥2.5% decrease from baseline; * fasting capillary glucose level should not exceed 140 mg/dL (7.8 mmol/L) more than three times in the past week (based on measuring capillary glucose levels a minimum of 7 times in a seven day period); * 2-hour post-prandial capillary glucose should not exceed 180 mg/dl (10.0 mmol/L) more than three times in the past week (based on measuring capillary glucose levels a minimum of 21 times in a seven day period); * fasting serum glucose level ≤126 mg/dL (7.0 mmol/L); if the fasting serum glucose level is \>126 mg/dL (7.0 mmol/L), it must be confirmed in an additional one out of two measurements; * evidence of endogenous insulin production defined as fasting or stimulated C-peptide levels ≥0.5 ng/mL (0.16 nmol/L).

  1 year following the first islet transplant

Study Arms (1)

1

EXPERIMENTAL

Allogeneic islets of Langerhans

Biological: Allogeneic islets of Langerhans transplant; Drug: Raptiva; Drug: Sirolimus; Drug: anti-thymocyte globulin

Interventions

Allogeneic islets of Langerhans transplant BIOLOGICAL

Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. Each infusion to contain at least 5,000 islet equivalents/kg body weight.

Also known as: Islets

1

Raptiva DRUG

Treatment Day -1 pretransplant to Treatment Day 90 after tx.: 1.0 mg/kg/wk SQ; Treatment Day 91 to Treatment Day 365: 0.5 mg/kg/wk SQ;

Also known as: Efalizumab

1

Sirolimus DRUG

Initial dose 0.1 mg/kg PO on day -2, followed by 0.05 mg/kg daily, whole blood 24-hour trough adjusted to target 3-15 ng/ml as tolerated

Also known as: Rapamune

1

anti-thymocyte globulin DRUG

2.0 mg/kg on days -2, and -1 IV

Also known as: ATG, Thymoglobulin

1

Eligibility Criteria

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

You may qualify if:

• Primary islet allotransplant
• Type I diabetes mellitus for a minimum of 5 years
• One of the following signs or symptoms despite intensive efforts made in close cooperation with their diabetic care team:
• Metabolic lability/instability characterized by hypoglycemia or ketoacidosis (\>2 hospital admissions in the previous year), erratic glucose profiles (MAGE\>120 mg/dL), or disruption in lifestyle of danger to life, self or others
• Reduced awareness of hypoglycemia or \>1 episode in the last 1.5 years of severe hypoglycemia
• Persistently poor glucose control (as defined by HgbA1c\>10% at the end of six months of intensive management efforts with the diabetes care team)
• Progressive secondary complications as defined by (i) a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically significant macular edema or therapy with photocoagulation during the last year; or (ii) urinary albumin excretion rate \>300 mg/day but proteinuria \<3g/day; or (iii) symptomatic autonomic neuropathy (as defined by postural hypotension in the setting of euvolemia, gastroparesis or diarrhea attributed to diabetic neuropathy, or neuropathic bladder as diagnosed by an urologist)
• Age 18 to 65 years of age.

You may not qualify if:

• Current use of immunosuppressive agents
• Lymphopenia (\<1000/µL) or leukopenia (\<3000 total leukocytes/µL)
• Presence of panel-reactive anti-HLA antibody \>20%
• Positive lymphocytotoxic cross-match using donor lymphocytes and serum
• Evidence of acute EBV infection (IgM\>IgG) OR negative screen for EBV by IgG determination
• Calculated or measured GFR \< 60 ml/min/m2
• Portal hypertension or history of significant liver disease
• History of malignancy within 10 years (except for adequately treated basal or squamous cell CA of the skin)
• Active peptic ulcer disease
• Severe unremitting diarrhea or other GI disorders potentially interfering with the ability to absorb oral medications
• Untreated proliferative retinopathy
• Pregnancy or breastfeeding
• Female subjects not post-menopausal or surgically sterile, or not using an acceptable method of contraception
• Active infections
• Serologic evidence of infection with HIV, or HbsAg or HCV Ab positive

Sponsors & Collaborators

• University of Minnesota: lead
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

Universtiy of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Diabetes Mellitus

Interventions

efalizumab; Sirolimus; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Limitations and Caveats

Early termination due to Raptiva being withdrawn from market

Results Point of Contact

• Title: Bernhard J. Hering, M.D.
• Organization: University of Minnesota

bhering@umn.edu

612-626-5735

Study Officials

• Bernhard J. Hering, M.D.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2008
• First Posted: May 6, 2008
• Study Start: November 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: August 1, 2012
• Last Updated: October 25, 2017
• Results First Posted: March 27, 2013

Record last verified: 2017-09

Locations

US (1)