NCT02727608

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_2 diabetes-mellitus

Timeline
Completed

Started May 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 29, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 4, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

May 15, 2016

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2018

Completed
Last Updated

October 4, 2018

Status Verified

October 1, 2018

Enrollment Period

2 years

First QC Date

March 29, 2016

Last Update Submit

October 3, 2018

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

  • 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.

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

Secondary Outcomes (7)

  • 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).

  • Monitoring of islet-function and survival.

    14, 30 and 75 days post-transplant.

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

    From start of infusion until 75 days post-transplant.

  • Patient and graft survival at 75 days post treatment.

    From start of infusion until 75 days post-transplant.

  • Estimated glomerular filtration rate (GFR) (Cystatin C)

    At day 75

  • +2 more secondary outcomes

Other Outcomes (2)

  • The percentage of loss of radioactivity in the liver field.

    Within the first two hours after start of islet infusion.

  • Effect of eculizumab on IBMIR

    Post infusion

Study Arms (1)

Eculizumab

EXPERIMENTAL

Intravenous infusion

Drug: Eculizumab

Interventions

EculizumabDRUG

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

Also known as: Soliris
Eculizumab

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • History of drug or alcohol abuse within the last year

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Uppsala, 752 37, Sweden

Location

Related Publications (8)

  • Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060.

    PMID: 15983207BACKGROUND

  • Eich T, Eriksson O, Lundgren T; Nordic Network for Clinical Islet Transplantation. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med. 2007 Jun 28;356(26):2754-5. doi: 10.1056/NEJMc070201. No abstract available.

    PMID: 17596618BACKGROUND

  • Eich T, Eriksson O, Sundin A, Estrada S, Brandhorst D, Brandhorst H, Langstrom B, Nilsson B, Korsgren O, Lundgren T. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Transplantation. 2007 Oct 15;84(7):893-8. doi: 10.1097/01.tp.0000284730.86567.9f.

    PMID: 17984843BACKGROUND

  • Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R, Ostraat O, Salmela K, Tibell A, Tufveson G, Elgue G, Nilsson Ekdahl K, Korsgren O, Nilsson B. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002 Dec 21-28;360(9350):2039-45. doi: 10.1016/s0140-6736(02)12020-4.

    PMID: 12504401BACKGROUND

  • Bennet W, Sundberg B, Groth CG, Brendel MD, Brandhorst D, Brandhorst H, Bretzel RG, Elgue G, Larsson R, Nilsson B, Korsgren O. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes. 1999 Oct;48(10):1907-14. doi: 10.2337/diabetes.48.10.1907.

    PMID: 10512353BACKGROUND

  • Koh A, Senior P, Salam A, Kin T, Imes S, Dinyari P, Malcolm A, Toso C, Nilsson B, Korsgren O, Shapiro AM. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation. 2010 Feb 27;89(4):465-71. doi: 10.1097/TP.0b013e3181c478fd.

    PMID: 20177350BACKGROUND

  • Eriksson O, Eich T, Sundin A, Tibell A, Tufveson G, Andersson H, Felldin M, Foss A, Kyllonen L, Langstrom B, Nilsson B, Korsgren O, Lundgren T. Positron emission tomography in clinical islet transplantation. Am J Transplant. 2009 Dec;9(12):2816-24. doi: 10.1111/j.1600-6143.2009.02844.x. Epub 2009 Oct 21.

    PMID: 19845588BACKGROUND

  • Friberg AS, Brandhorst H, Buchwald P, Goto M, Ricordi C, Brandhorst D, Korsgren O. Quantification of the islet product: presentation of a standardized current good manufacturing practices compliant system with minimal variability. Transplantation. 2011 Mar 27;91(6):677-83. doi: 10.1097/TP.0b013e31820ae48e.

    PMID: 21248660BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Gunnar Tufveson, MD, PhD

    Uppsala University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 29, 2016

First Posted

April 4, 2016

Study Start

May 15, 2016

Primary Completion

May 1, 2018

Study Completion

June 1, 2018

Last Updated

October 4, 2018

Record last verified: 2018-10

Data Sharing

IPD Sharing
Will not share

Locations

SE(1)