MGA031, Sirolimus and Tacrolimus in Islet Transplantation

NCT00265473 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 0407M62505
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is designed to extend the observations made in our pilot clinical trial (IND 8971, Study #1) on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune destruction of deceased donor pancreatic islet transplants in type 1 diabetic recipients.

Conditions

Type 1 Diabetes Mellitus; Hypoglycemia

Outcome Measures

Primary Outcomes (2)

• Subjects With Full Islet Function.

  Proportion of subjects with full islet function (i.e. insulin independent) at one year after initial islet transplant.

  At one year after initial transplant.

• Serious Adverse Events Related to Immunosuppressive Therapy.

  Number of serious adverse events related to immunosuppressive therapy.

  Day 0 - Day 365

Secondary Outcomes (3)

• Subjects With Partial Islet Function and no Episodes of Severe Hypoglycemia;

  At one year after initial transplant

• Insulin Independent Single-donor Subjects.

  At 75 days after transplant

• Insulin Independent Multiple-donor Subjects.

  At one year after final transplant

Study Arms (1)

Allogeneic Islets of Langerhans

EXPERIMENTAL

Islet infusion

Biological: Allogeneic Islets of Langerhans

Interventions

Allogeneic Islets of Langerhans BIOLOGICAL

Intraportal infusion of islets of Langerhans

Allogeneic Islets of Langerhans

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study.
• 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.
• Absent stimulated C-peptide (\<0.3ng/ml) in response to a mixed meal tolerance test.
• 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 or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration).
• Reduced awareness of hypoglycemia.

You may not qualify if:

• Any previous transplant.
• BMI \>27 kg/m2 or patient weight ≤ 50kg.
• Insulin requirement of \> 0.8 IU/kg/day or 50 IU/day.
• HbA1c \>10%.
• Untreated proliferative diabetic retinopathy.
• Uncontrolled Hypertension.
• Estimated glomerular filtration rate \<70 ml/min/1.73 m2 for females and \<80 ml/min/1.73 m2 for males
• Presence or history of macroalbuminuria (\>300mg/d).
• Presence or history of panel-reactive anti-HLA antibodies \>20% by flow cytometry.
• Females: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. Males: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception.
• Active infection.
• Negative screen for Epstein-Barr Virus (EBV).
• Invasive aspergillus infection within one year prior to study entry.
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• Active alcohol, tobacco or substance abuse.

Sponsors & Collaborators

• University of Minnesota: lead
• National Institutes of Health (NIH): collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Melena D. Bellin, MD
• Organization: Schulze Diabetes Institute, University of Minnesota

bell0130@umn.edu

612-625-4686

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: December 12, 2005
• First Posted: December 14, 2005
• Study Start: November 1, 2005
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: March 9, 2017
• Results First Posted: September 21, 2011

Record last verified: 2017-01

Locations

US (1)