Complement Inhibitor Eculizumab in Clinical Islet Transplantation (ICC)

October 3, 2018 updated by: Uppsala University

Induction With Complement Inhibitor Eculizumab in Clinical Islet Transplantation

This is a dual centre, single arm, exploratory study of the possibility to use eculizumab (Soliris) to prevent/reduce destruction of islets of Langerhans after portal infusion of the islets in patients with diabetics accepted for islet transplant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a dual centre, single arm, exploratory study of the possibility to use eculizumab (Soliris) to prevent/reduce destruction of islets of Langerhans after portal infusion of the islets in patients with diabetics accepted for islet transplant. Ten patients from 2 centres (Uppsala University Hospital and Karolinska University Hospital in Stockholm) will be transplanted. The purpose of the study is to investigate if selective complement inhibition by eculizumab combined with standard anticoagulation during and after transplantation can further reduce the extent of early tissue loss after portal infusion of islets.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Uppsala, Sweden, 752 37
        • Dept of Surgical Sciences, Section of Transplantation Surgery, University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients between 18 to 65 years of age
  • Patients able to provide written informed consent
  • Absent stimulated c-peptide (< 0.1 nmol/L). This includes also previously islet-transplanted patients with no detectable c-peptide.
  • Patients at fear of severe hypoglycemia
  • Female patients of child bearing potential must have a negative pregnancy test (s-β-HCG) and must be practicing an effective, reliable medical accepted contraceptive regimen while on eculizumab treatment and to study end at 75 days.
  • Patients vaccinated against Neisseria meningitides or patients accepting adequate antibiotic prophylaxis

Exclusion Criteria:

  • Body mass index > 30 kg/m2
  • Untreated proliferative diabetes retinopathy
  • Recipient of any other concomitant organ transplantation - Glomerular filtration rate < 50 mL/min before first islet transplantation
  • Positive T-cell cross-matching by Complement Depending Cytotoxicity (CDC)
  • Pregnancy or lactating
  • Active ongoing infection, bacterial or viral
  • Unresolved meningococcal disease
  • Known bleeding disorder
  • Known complement disorder
  • Have received any other investigational drug within 30 days before inclusion
  • History of drug or alcohol abuse within the last year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eculizumab
Intravenous infusion
Drug: Eculizumab
Intravenous infusion (1200 mg) over 35 minutes. Consecutive infusions (900 mg) on Days 1, 7 and 14.
Other Names:
  • Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Increased survival of ICC´s transplanted as measured by peak c-peptide
Time Frame: During and within two hours post infusion (day 0).
Determined by PET-scan of 2-deoxy-27fluoro-D-glucose (18F) (FDG)-labelled islets infused in the portal vein.
During and within two hours post infusion (day 0).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of eculizumab on instant blood mediated inflammatory reaction (IBMIR) as determined by complement activation.
Time Frame: At the end of infusion and 1 and 2 h post start of infusion (day 0).
Extent of early tissue loss
At the end of infusion and 1 and 2 h post start of infusion (day 0).
Monitoring of islet-function and survival.
Time Frame: 14, 30 and 75 days post-transplant.
Evaluation of insulin-independency, the extent of reduction of baseline insulin requirement, continuous glucose monitoring system (CGMS) performance, HbA1c, number of hypoglycemic events per week.
14, 30 and 75 days post-transplant.
Adverse events (AEs) and serious adverse events (SAEs)
Time Frame: From start of infusion until 75 days post-transplant.
Will be assigned Medical Drug Regulatory Activities (MedDRA) preferred terms and tabulated as incidence rate
From start of infusion until 75 days post-transplant.
Patient and graft survival at 75 days post treatment.
Time Frame: From start of infusion until 75 days post-transplant.
Graft survival is measured by measurable stimulated c-peptide (>0,1 nmol/L)
From start of infusion until 75 days post-transplant.
Estimated glomerular filtration rate (GFR) (Cystatin C)
Time Frame: At day 75
Cystatin C value
At day 75
Portal vein thrombosis
Time Frame: The day after infusion
Assessment by per protocol ultrasound
The day after infusion
Bleeding
Time Frame: From infusion until 2 hours post start of infusion
will be assessed by hemoglobin and thrombocyte monitoring (important while portal vein catheter is in place and withdrawn (within first week).
From infusion until 2 hours post start of infusion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of loss of radioactivity in the liver field.
Time Frame: Within the first two hours after start of islet infusion.
When logistically feasible. Determined by positron emission tomography (PET)-scan of 2-deoxy-27fluoro-D-glucose ((18F) (FDG)-labelled islets infused in the portal vein as assessed during treatment (only possible at the Uppsala site).
Within the first two hours after start of islet infusion.
Effect of eculizumab on IBMIR
Time Frame: Post infusion
Determined by coagulation activation (TAT)
Post infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Uppsala University

Investigators

  • Principal Investigator: Gunnar Tufveson, MD, PhD, Uppsala University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2016

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

June 1, 2018

Study Registration Dates

First Submitted

March 29, 2016

First Submitted That Met QC Criteria

March 29, 2016

First Posted (Estimate)

April 4, 2016

Study Record Updates

Last Update Posted (Actual)

October 4, 2018

Last Update Submitted That Met QC Criteria

October 3, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICC version 2
  • 2014-005421-12 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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