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

Study Overview
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Brief Summary
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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.

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

Conditions
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Atypical Hemolytic Uremic Syndrome

Intervention / Treatment
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* Other: Eculizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently receiving eculizumab treatment in the M11-001 aHUS Registry Two normal platelet counts at least 4 weeks apart Two normal lactate dehydrogenase levels at least 4 weeks apart Willing, committed, and able to return for all clinic visits and complete all study-related procedures 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: Any prior eculizumab treatment discontinuation On chronic dialysis (defined as ≥3 months on dialysis) Currently participating in another complement inhibitor trial Life expectancy of <6 months 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)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Eculizumab<br>The targeted population consists of pediatric and adult participants with aHUS who received eculizumab at the discretion of the treating physician. | Other: Eculizumab<br>* 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.<br>* Other names: Soliris®;|

What is the study measuring?
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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 |