Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation

NCT01327573 | Completed Phase 1 Results

• 1 other identifier: 100700716
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney. The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.

Conditions

Kidney; Complications, Allograft

Keywords

chronic kidney allograft injury; complement protein; eculizumab; Kidney transplantation

Outcome Measures

Primary Outcomes (3)

• Baseline eGFR (Estimated Glomerular Filtration Rate)

  Baseline

• Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6

  Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.

  Months 2,3,4,5,6

• Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR)

  These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".

  6 months

Study Arms (2)

Eculizumab

EXPERIMENTAL

eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone)

Drug: eculizumab

no additional therapy

NO INTERVENTION

patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy

Interventions

eculizumab DRUG

* Eculizumab Induction 600mg IV every 7 days for 4 doses * Eculizumab 900mg IV 7 days later * Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks

Also known as: h5G1.1-mAb, Soliris

Eculizumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Kidney transplant recipients greater than 6 months from the date of transplant
• Must be on standard immunosuppression: tacrolimus, mycophenolate mofetil, prednisone and have stable tacrolimus trough levels over past 3 months
• Deteriorating renal function, as defined by 20% reduction in GFR (MDRD calculation)
• Presence of DSA, as defined as MFI \> 1100
• Renal biopsy demonstrating no diffuse, irreversible end-stage organ injury (i.e. stage IV Fibrosis)
• Renal biopsy demonstrating C4d deposition (stratum 1) or no C4d deposition (stratum 2)

You may not qualify if:

• History of CMV, BK, HSV or other viral infections
• History of chronic, recurrent bacterial infections
• Evidence of tubulitis on renal biopsy or other morphological features of acute cellular rejection or acute humoral rejection
• Renal biopsy demonstrating diffuse, irreversible end-stage organ injury
• Absolute GFR \< 25 (MDRD calculation)
• Inability to provide informed consent
• History of poor vascular access
• Refusal to use double barrier contraception during study participation
• Patients actively enrolled in other clinical trials

Sponsors & Collaborators

• Sanjay Kulkarni: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

Related Publications (5)

• Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004 Mar;4(3):438-43. doi: 10.1111/j.1600-6143.2004.00360.x.

  PMID: 14961999 BACKGROUND

• Worthington JE, McEwen A, McWilliam LJ, Picton ML, Martin S. Association between C4d staining in renal transplant biopsies, production of donor-specific HLA antibodies, and graft outcome. Transplantation. 2007 Feb 27;83(4):398-403. doi: 10.1097/01.tp.0000251430.11723.b6.

  PMID: 17318071 BACKGROUND

• Al-Lamki RS, Bradley JR, Pober JS. Endothelial cells in allograft rejection. Transplantation. 2008 Nov 27;86(10):1340-8. doi: 10.1097/TP.0b013e3181891d8b.

  PMID: 19034000 BACKGROUND

• Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30.

  PMID: 18055865 BACKGROUND

• Davin JC, Gracchi V, Bouts A, Groothoff J, Strain L, Goodship T. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation. Am J Kidney Dis. 2010 Apr;55(4):708-11. doi: 10.1053/j.ajkd.2009.08.011. Epub 2009 Oct 25.

  PMID: 19854549 BACKGROUND

MeSH Terms

Interventions

eculizumab

Results Point of Contact

• Title: Dr. Sanjay Kulkarni
• Organization: Yale University

sanjay.kulkarni@yale.edu

203-785-6501

Study Officials

• Sanjay Kulkarni, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 1, 2011
• Study Start: March 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: August 12, 2019
• Results First Posted: August 12, 2019

Record last verified: 2019-07

Locations

US (1)