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

Alexion Pharmaceuticals, Inc.67 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

EculizumabOTHER

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.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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)

Locations (24)

Clinical Trial Site

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

Clinical Trial Site

Atlanta, Georgia, United States

Clinical Trial Site

Chicago, Illinois, United States

Clinical Trial Site

Boston, Massachusetts, United States

Clinical Trial Site

Hackensack, New Jersey, United States

Clinical Trial Site

Charlotte, North Carolina, United States

Clinical Trial Site

Columbus, Ohio, United States

Clinical Trial Site

Houston, Texas, United States

Clinical Trial Site

Adelaide, Australia

Clinical Trial Site

Clayton, Australia

...and 14 more locations

Outcomes

Primary Outcomes

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.

Time frame: Baseline, 24 Months

Secondary Outcomes

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.

Time frame: 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.

Time frame: Baseline, 24 Months