- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01653899
Caspase Inhibition in Islet Transplantation
Improving Engraftment, Islet Survival and Metabolic Reserve in Clinical Islet Transplantation Using Caspase Inhibitor - IDN-6556
This is an Investigator Initiated, Phase I/II study, where Type 1 diabetic participants will receive a 14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following their first islet transplant. Two pilot studies are proposed to establish the optimal safety and efficacy dose of IDN-6556 (25 mg twice daily (Pilot 1) or a loading dose of 100 mg two hours prior to transplantation, then two 50 mg doses following transplant (Day 0) (Pilot 2). This will be followed by 50 mg three times daily). Participants of both pilot studies will receive islet cell transplants under the University of Alberta's standard-of-care therapy.
Secondary objectives include:
- To determine the proportion of subjects treated with IDN-6556 who achieve and maintain insulin independence after the first or subsequent islet transplant.
- To obtain preliminary data on the efficacy of IDN-6556 to maintain adequate immunological protection against both allo- and autoimmunity of islet transplant recipients.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Alberta
-
Edmonton, Alberta, Canada
- University of Alberta
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
To be eligible the participant must have had T1DM for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
- Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥ 4, HYPO score ≥ 1,000, lability index (LI) ≥ 400 or combined Hypo/LI > 400/300
- Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
Exclusion Criteria:
- Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent myocardial infarction (within past 6 months); (b) left ventricular ejection fraction < 30%; or (c) evidence of ischemia on functional cardiac exam.
- Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to transplant).
- Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
- History of non-adherence to prescribed regimens.
- Active infection including Hepatitis C, Hepatitis B, HIV, TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
- Any history of or current malignancies except squamous or basal skin cancer.
- BMI > 35 kg/m2 at screening visit.
- Age less than 18 or greater than 68 years.
- Measured glomerular filtration rate (GFR) < 60 mL/min/1.73 m2.
- Presence or history of macroalbuminuria (> 300 mg/g creatinine).
- Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
- Baseline Hb < 105g/L (< 10.5 g/dL) in women, or < 120 g/L (< 12 g/dL) in men.
- Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values > 1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
- Untreated proliferative retinopathy.
- Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding.
- Previous transplant or evidence of significant sensitization on PRA (at the discretion of the investigator).
- Insulin requirement > 1.0 U/kg/day
- HbA1C > 12%.
- Uncontrolled hyperlipidemia [fasting LDL cholesterol > 3.4 mmol/L (133 mg/dL), treated or untreated; and/or fasting triglycerides > 2.3 mmol/L (90 mg/dL)].
- Under treatment for a medical condition requiring chronic use of steroids.
- Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5.
- Untreated Celiac disease.
- Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IDN-6556
Drug
|
14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following first islet transplant at 50mg twice daily.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the safety of the IDN-6556 caspase inhibitor in adult Type 1 diabetic participants receiving their first islet transplant
Time Frame: 3 years post-initial transplant
|
The primary objective of this protocol is to assess the safety of the IDN-6556 caspase inhibitor in adult Type 1 diabetic participants receiving their first islet transplant.
A tracking log will document adverse events and unexpected complications associated with IDN-6556 using a grading classification as per protocol.
|
3 years post-initial transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1. To determine the proportion of subjects treated with IDN-6556 who achieve and maintain insulin independence after the first or subsequent islet transplant.
Time Frame: 3 years post-initial transplant
|
The proportion of study participants achieving and maintaining insulin independence (c-peptide, HbA1c level) with good glycemic control (blood sugar measurement) at Day 90 and 1, 2, 3 years post-initial islet transplant.
|
3 years post-initial transplant
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2. To obtain preliminary data on the efficacy of IDN-6556 to maintain adequate immunological protection against both allo- and autoimmunity of islet transplant recipients.
Time Frame: 3 years post-initial transplant
|
Immune monitoring for HLA and panel reactive antibody will be performed using serum samples
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3 years post-initial transplant
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: A.M. James Shapiro, MD PhD, University of Alberta
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 (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- Pro00024049
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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