- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00285194
hOKT3γ1 (Ala-Ala) Combined With Sirolimus and Delayed Tacrolimus in Type 1 Diabetic Islet Allograft Recipients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is an open-label, one-year follow-up study of type 1 diabetic islet allograft recipients who receive FcR non-binding OKT3 antibody hOKT3γ1 (Ala-Ala) plus sirolimus induction immunotherapy combined with sirolimus and delayed tacrolimus maintenance immunosuppression. Six subjects were transplanted.
The premise behind the proposal is that hOKT3γ1(Ala-Ala) corrects the imbalance between autoreactive and regulatory T cells and consequently prevents autoimmune destruction of transplanted islets. To prevent allorejection, hOKT3γ1(Ala-Ala)was combined with sirolimus and delayed tacrolimus. Additionally, the safety and efficacy of the maintenance immunosuppressive regimen of sirolimus combined with tacrolimus was monitored.
Study Type
Enrollment
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Universtiy of Minnesota
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Primary islet allotransplant
Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:
- Metabolic lability/instability;
- Reduced awareness of 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.
- Age 18 and older
- Able to give written informed consent
Exclusion Criteria:
- Age less than 18 years
- Body weight greater than75 kg.
- BMI greater than 26 kg/m2 for male and females
- Waist-to-hip ratio 0.80 (female) and 0.95 (male)
- First degree relative with type 2 diabetes
- Insulin requirement of greater than 0.7 IU/kg/day
- HbA1C greater than 12%
- Positive C-peptide response to intravenous arginine stimulation
- Untreated proliferative retinopathy
- Macroalbuminuria (urinary albumin excretion greater than 300 mg/24hrs)
- Creatinine clearance greater than 85 ml/min/1.73 m2 in females, greater than 95 ml/min/1.73 m2 in males
- Serum creatinine greater than 1.2 mg/dl
- Previous pancreas or islet transplant
- Previous OKT3 antibody therapy
- Presence of history of panel-reactive anti-HLA antibodies greater than 10%
- Abnormal T4 and TSH despite thyroid replacement therapy
- Positive pregnancy test, or presently breast-feeding
- Active infection
- Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
- Invasive aspergillus infection within year prior to study entry
- Any history of malignancy
- Active alcohol or substance abuse
- History of non-adherence to prescribed regimens
- Psychiatric disorder making the subject not a suitable candidate for transplantation
- Karnofsky performance score greater than 70
- Baseline Hgb greater than 11.7 g/dl; lymphopenia (greater than 1,000/L), or leukopenia (greater than 4,000 total leukocytes/L), or an absolute CD4+ count <500/L
- Thrombocytopenia greater than 150 x 109/L
- Use of warfarin or other anticoagulant therapy (except aspirin) or patient with PT-INR greater than 1.5
- Severe co-existing cardiac disease
- Baseline liver function tests outside of normal range
- Presence of gallstones on baseline ultrasound exam
- Active peptic ulcer disease
- Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- Celiac disease
- Hyperlipidemia (fasting LDL cholesterol greater than 130 mg/dl, treated or untreated; and/or fasting triglycerides greater than 200 mg/dl)
- Addison's disease.
- Under treatment for a medical condition requiring chronic use of systemic steroids
- Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Safety, tolerability, immune activity, and pharmacokinetics of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of allogeneic islet transplants as measured by:
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-Physical examination
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-Vital signs
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-Body weight
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-Adverse events
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-Laboratory and diagnostic safety assessments included complete blood counts with differential and platelets, circulating T cell phenotypes, and serum chemistry.
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-Immune activity and pharmacokinetic assessments included hOKT3γ1 (Ala-Ala) level and half-life, monoclonal antibody coating and modulation of CD3 on peripheral blood T cells, and anti-hOKT3γ1 (Ala-Ala) antibody responses.
|
Secondary Outcome Measures
Outcome Measure |
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Efficacy of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of islet transplants as defined by:
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-Proportion of subjects with full islet graft function (insulin independence and HbA1c <7%);
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-Proportion of subjects with partial islet graft function (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/ml and HbA1c <7%);
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-Proportion of subjects with slet graft loss will be defined as a return to insulin therapy for >30 days, absence of basal and arginine-stimulated C-peptide, re-transplantation, or patient death;
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Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0003M44181
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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