Prevention of Delayed Graft Function Using Eculizumab Therapy (PROTECT Study)

NCT02145182 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ECU-DGF-2012013-004650-25
• Study Type: interventional
• Target: 288
• Locations: 9 countries
• Sites: 78

Brief Summary

The purpose of this study was to determine if eculizumab is safe and could be used to prevent delayed graft function (DGF) following kidney transplantation.

Conditions

Delayed Graft Function

Keywords

DGF; Dialysis; Kidney; Kidney Transplantation; eGFR; Complement; Eculizumab

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants With Delayed Graft Function (DGF) In The First Seven Days Post-transplant

  Results are reported for the DGF composite endpoint, defined as the occurrence of DGF (dialysis for any reason in the first 7 days post transplantation), graft loss, death, or loss to follow-up (including discontinuation) in the first 7 days post transplantation and for each item of the composite endpoint. Loss to follow-up included withdrawal due to any reason other than death. The sum of the counts in the events that make up the DGF composite may be greater than the composite count, because a participant who experienced multiple events was only counted once in the composite.

  First 7 days post transplantation

Secondary Outcomes (4)

• Percentage Of Participants With DGF, Functional DGF, And Immediate Graft Function

  First 7 days post transplantation

• Percentage Of Participants Who Required Dialysis Post Transplantation

  First 30 days post transplantation

• Estimated Glomerular Filtration Rate (eGFR)

  Day 28 post transplantation

• Percentage Of Participants With Rejection-free Graft Survival

  Week 26 and 52 post transplantation

Study Arms (2)

Active

EXPERIMENTAL

Eculizumab was administered by intravenous (IV) infusion over 25-45 minutes (min) for 2 doses (on the day of transplant then 18-24 hours \[h\] later).

Drug: Eculizumab

Placebo

PLACEBO COMPARATOR

Placebo was administered by IV infusion over 25-45 min for 2 doses (on the day of transplant then 18-24 h later).

Drug: Placebo

Interventions

Eculizumab DRUG

Eculizumab is a complement component 5 inhibitor.

Also known as: Soliris

Active

Placebo DRUG

0.9% sodium chloride

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, 18 years or older
• Has dialysis-dependent renal failure (initiated more than 2 months prior to transplant)
• Participant is to receive a first kidney transplant from a standard criteria donor or expanded criteria donor deceased donor with a DGF risk score using the Irish scale of ≥25% (to be determined prior to surgery and before randomization)
• Able to provide written informed consent
• Willing and able to comply with the requirements of the study protocol
• Female participants of child-bearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) and must be practicing an effective, reliable, and medically approved contraceptive regimen at the time of consent and for up to 5 months following discontinuation of treatment

You may not qualify if:

• Participant to receive a multi-organ transplant
• Participant to receive kidney(s) from donors \<6 years of age
• Participant to receive a dual kidney transplant (from same donor, including en bloc)
• Participant to receive a living donor kidney
• Participant is highly sensitized (high risk to develop acute antibody-mediated rejection) to the donor (as determined by local center practice). Testing to determine high risk may include but is not limited to flow cytometric cross match, single antigen bead testing and/or complement dependent cytotoxicity
• Participant has received a previous transplant
• Participant is participating in another investigational study
• Participant has a body mass index \>40 kilograms/square meter at screening
• Participant will be the recipient of an A, B, O Blood Glycoproteins (ABO) (blood type) incompatible kidney (A2 donors to B and O recipients will be allowed if the site has the ability to confirm A2 subtype)
• Participant will receive a kidney from a donation after cardiac death donor
• Participant has a predicted Irish model risk of DGF \<25%
• Female participants who are pregnant or breast feeding
• Female participants of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception
• Participants with a history of human immunodeficiency virus, or active hepatitis C virus or hepatitis B virus infection
• Participants with active bacterial or other infection which is clinically significant in the opinion of the Investigator

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (78)

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Birmingham, Alabama, 35294, United States

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Phoenix, Arizona, 85054, United States

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Los Angeles, California, 90024, United States

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Palo Alto, California, 94304, United States

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San Francisco, California, 94115, United States

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San Francisco, California, 94143, United States

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Aurora, Colorado, 80045, United States

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New Haven, Connecticut, 06520, United States

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Washington D.C., District of Columbia, 20007, United States

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Tampa, Florida, 33606, United States

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Augusta, Georgia, 30912, United States

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Chicago, Illinois, 60612, United States

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Lexington, Kentucky, 40536, United States

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New Orleans, Louisiana, 70121, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02215, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55455, United States

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St Louis, Missouri, 63110, United States

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Livingston, New Jersey, 07039, United States

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New York, New York, 10032, United States

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New York, New York, 10065, United States

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The Bronx, New York, 10467, United States

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Chapel Hill, North Carolina, 27599, United States

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Winston-Salem, North Carolina, 27157, United States

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Charleston, South Carolina, 29425, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77030, United States

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Charlottesville, Virginia, 22903, United States

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Richmond, Virginia, 23298, United States

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Seattle, Washington, 98195, United States

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Camperdown, New South Wales, Australia

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Westmead, New South Wales, Australia

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Adelaide, South Australia, Australia

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Clayton, Victoria, 3168, Australia

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Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, 05403-000, Brazil

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Prague, 14000, Czechia

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Bordeaux, 33076, France

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Créteil, 94010, France

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Le Kremlin-Bicêtre, 94270, France

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Lyon, 69003, France

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Nantes, 44093, France

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Paris, 75010, France

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Paris, 75743, France

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Strasbourg, 67091, France

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Suresnes, 92150, France

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Toulouse, 31059, France

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Tours, 37044, France

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Berlin, 13353, Germany

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Dresden, 01307, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Hamburg, 20246, Germany

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Hannoversch Münden, 34346, Germany

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Hanover, 30625, Germany

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Kiel, 24105, Germany

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Bari, 70124, Italy

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Brescia, 25123, Italy

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Milan, 20162, Italy

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Padua, 35128, Italy

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Torino, 10126, Italy

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Verona, 37126, Italy

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Badalona, 08916, Spain

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Barcelona, 08003, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Barcelona, 08907, Spain

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Madrid, 28041, Spain

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Santander, 39008, Spain

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Seville, 41013, Spain

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Valencia, 46017, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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MeSH Terms

Conditions

Delayed Graft Function

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Because the study failed to demonstrate a treatment effect and the program subsequently lost funding, all collected data could not be analyzed to generate summary level data.

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 22, 2014
• Study Start: August 21, 2014
• Primary Completion: November 22, 2016
• Study Completion: November 22, 2016
• Last Updated: December 17, 2018
• Results First Posted: December 17, 2018

Record last verified: 2018-12

Locations

CZ (1); AU (4); DE (8); US (32); FR (11); CA (4); IT (6); ES (11); BR (1)