Complement Inhibitor Eculizumab in Clinical Islet Transplantation

Phase 2

Completed

• Conditions: Diabetes Mellitus
• Interventions: Drug: Eculizumab

• Registration Number: NCT02727608
• Lead Sponsor: Uppsala University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2016-03-29
• Study First Submitted QC: 2016-03-29
• Study First Posted: 2016-04-04
• Study Start: 2016-05-15
• Primary Completion: 2018-05
• Study Completion: 2018-06
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-03
• Last Update Posted: 2018-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eculizumab	Eculizumab	Intravenous infusion

Primary Outcome Measures

Name	Time	Method
Increased survival of ICC´s transplanted as measured by peak c-peptide	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.

Secondary Outcome Measures

Name	Time	Method
Effect of eculizumab on instant blood mediated inflammatory reaction (IBMIR) as determined by complement activation.	At the end of infusion and 1 and 2 h post start of infusion (day 0).	Extent of early tissue loss
Bleeding	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).
Estimated glomerular filtration rate (GFR) (Cystatin C)	At day 75	Cystatin C value
Adverse events (AEs) and serious adverse events (SAEs)	From start of infusion until 75 days post-transplant.	Will be assigned Medical Drug Regulatory Activities (MedDRA) preferred terms and tabulated as incidence rate
Patient and graft survival at 75 days post treatment.	From start of infusion until 75 days post-transplant.	Graft survival is measured by measurable stimulated c-peptide (\>0,1 nmol/L)
Monitoring of islet-function and survival.	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.
Portal vein thrombosis	The day after infusion	Assessment by per protocol ultrasound

Trial Locations

Locations (1)

Dept of Surgical Sciences, Section of Transplantation Surgery, University Hospital; 🇸🇪 Uppsala, Sweden