Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment (EVIDENCE)

Evidence - Evaluation of Potential Predictors of Disease Progression in Patients With aHUS, Including Genetics, Biomarkers and Treatment

This was a prospective, open-label study with no participant randomization. Treatment for aHUS was observational and at the discretion of the treating physician. The purpose of this study was to assess disease manifestations of complement-mediated thrombotic microangiopathy (TMA) and evaluate potential clinical predictors of disease manifestations and progression in participants with aHUS with or without eculizumab treatment in the clinical setting.

Study Overview

• Status: Terminated
• Conditions: Atypical Hemolytic Uremic Syndrome
• Intervention / Treatment: Other: Eculizumab

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Clinical Trial Site
  • Clayton, Australia, 3168
    • Clinical Trial Site
  • Heidelberg, Australia, 3084
    • Clinical Trial Site
  • Kingswood, Australia, 2747
    • Clinical Trial Site
  • Liverpool, Australia, 2170
    • Clinical Trial Site
  • Nedlands, Australia, 6109
    • Clinical Trial Site
  • Parkville, Australia, 3052
    • Clinical Trial Site
  • Parkville, Australia, 3050
    • Clinical Trial Site
  • Perth, Australia, 6008
    • Clinical Trial Site
  • Westmead, Australia, 2145
    • Clinical Trial Site
  • Woolloongabba, Australia, 4102
    • Clinical Trial Site
• Germany
  • Hannover, Germany, 30625
    • Clinical Trial Site
  • Hannöver, Germany, 30625
    • Clinical Trial Site
  • Kiel, Germany, 24105
    • Clinical Trial Site
  • Luebeck, Germany, 23538
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom, NW3 2PF
    • Clinical Trial Site
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Clinical Trial Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Clinical Trial Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Clinical Trial Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Clinical Trial Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Clinical Trial Site
  • Texas
    • Houston, Texas, United States, 77030
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants with aHUS enrolled in the M11-001 aHUS Registry and currently receiving eculizumab with no prior intentional eculizumab discontinuations at any time (for example, not occasional, unplanned, or temporary missed doses of eculizumab, but intended long-term discontinuation).

Description

Inclusion Criteria:

1. Currently receiving eculizumab treatment in the M11-001 aHUS Registry
2. Two normal platelet counts at least 4 weeks apart
3. Two normal lactate dehydrogenase levels at least 4 weeks apart
4. Willing, committed, and able to return for all clinic visits and complete all study-related procedures
5. Participant or participant's parent/legal guardian must have been willing and able to give written informed consent. Participant (if minor) must have been willing to give written informed assent (if applicable as determined by the central Institutional Review Boards/Independent Ethics Committees)

Exclusion Criteria:

1. Any prior eculizumab treatment discontinuation
2. On chronic dialysis (defined as ≥3 months on dialysis)
3. Currently participating in another complement inhibitor trial
4. Life expectancy of <6 months
5. Participant or participant's parent/legal guardian was unable to give written informed consent. Participant (if minor) was unable to give written informed assent (if applicable as determined by the central Institutional Review Boards/Independent Ethics Committees)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Eculizumab; The targeted population consists of pediatric and adult participants with aHUS who received eculizumab at the discretion of the treating physician.	Other: Eculizumab; This study was an observational study. Therefore, the study drug was not provided as part of this study, and the dosing regimen was based solely at the discretion of the treating physician.; Other Names: Soliris®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate Of Thrombotic Microangiopathy (TMA) Manifestations During Eculizumab Treatment Compared To Off-Treatment	A TMA manifestation was defined as one of following: Hematologic or renal events due to aHUS; extra-renal clinical signs and symptoms of aHUS; tissue (for example, kidney transplant) biopsy demonstrating TMA due to aHUS. The study was terminated with only 20% of the planned enrollment and due to the subsequent loss of funding for the program, the samples collected for outcome measure assessment could not be analyzed to generate summary-level data. All participants enrolled in ECU-aHUS-403 were concurrently enrolled in protocol M11-001, and their data will be included in the analyses for M11-001.	Baseline, 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline To 24 Months In Estimated Glomerular Filtration Rate (eGFR)	Change in estimated eGFR over time using the chronic kidney disease-epidemiology (CKD-EPI) formula. The study was terminated with only 20% of the planned enrollment and due to the subsequent loss of funding for the program, the samples collected for outcome measure assessment could not be analyzed to generate summary-level data. All participants enrolled in ECU-aHUS-403 were concurrently enrolled in protocol M11-001, and their data will be included in the analyses for M11-001.	Baseline, 24 Months
Incidence Of Plasma Exchange And Plasma Infusion (PE/PI)	The number of occurrences of PE/PI per participant-years was calculated and summarized by treatment status. The study was terminated with only 20% of the planned enrollment and due to the subsequent loss of funding for the program, the samples collected for outcome measure assessment could not be analyzed to generate summary-level data. All participants enrolled in ECU-aHUS-403 were concurrently enrolled in protocol M11-001, and their data will be included in the analyses for M11-001.	Baseline, 24 Months

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2015
• Primary Completion (Actual): October 5, 2017
• Study Completion (Actual): October 5, 2017

Study Registration Dates

• First Submitted: November 24, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 12, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Disease; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Thrombotic Microangiopathies; Uremia; Disease Progression; Syndrome; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: ECU-aHUS-403; 2015-003135-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No