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

Terminated

Brief Summary: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Eculizumab	Eculizumab	The targeted population consists of pediatric and adult participants with aHUS who received eculizumab at the discretion of the treating physician.

Primary Outcome Measures

Name	Time	Method
Rate Of Thrombotic Microangiopathy (TMA) Manifestations During Eculizumab Treatment Compared To Off-Treatment	Baseline, 24 Months	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline To 24 Months In Estimated Glomerular Filtration Rate (eGFR)	Baseline, 24 Months	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.
Incidence Of Plasma Exchange And Plasma Infusion (PE/PI)	Baseline, 24 Months	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.