Complement Inhibitor Eculizumab in Clinical Islet Transplantation

Uppsala University3 enrolled

Overview

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

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus

Interventions

EculizumabDRUG

Intravenous infusion (1200 mg) over 35 minutes. Consecutive infusions (900 mg) on Days 1, 7 and 14.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Dept of Surgical Sciences, Section of Transplantation Surgery, University Hospital

Uppsala, Sweden

Outcomes

Primary Outcomes

Increased survival of ICC´s transplanted as measured by peak c-peptide

Determined by PET-scan of 2-deoxy-27fluoro-D-glucose (18F) (FDG)-labelled islets infused in the portal vein.

Time frame: During and within two hours post infusion (day 0).

Secondary Outcomes

Effect of eculizumab on instant blood mediated inflammatory reaction (IBMIR) as determined by complement activation.

Extent of early tissue loss

Time frame: At the end of infusion and 1 and 2 h post start of infusion (day 0).

Monitoring of islet-function and survival.

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.

Time frame: 14, 30 and 75 days post-transplant.

Adverse events (AEs) and serious adverse events (SAEs)

Will be assigned Medical Drug Regulatory Activities (MedDRA) preferred terms and tabulated as incidence rate

Time frame: From start of infusion until 75 days post-transplant.

Patient and graft survival at 75 days post treatment.

Graft survival is measured by measurable stimulated c-peptide (\>0,1 nmol/L)

Time frame: From start of infusion until 75 days post-transplant.

Estimated glomerular filtration rate (GFR) (Cystatin C)

Cystatin C value

Time frame: At day 75

Portal vein thrombosis

Assessment by per protocol ultrasound

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.