Atypical Hemolytic Uremic Syndrome
Conditions
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.
Interventions
OTHEREculizumab
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.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Germany, United Kingdom, United States
Participant flow
Pre-assignment details
Sixty-seven participants were enrolled in this study (15 pediatric and 52 adults). Treatment information was missing for 1 adult participant.
Participants by arm
| Arm | Count |
|---|---|
| Pediatric Participants with aHUS who were less than 18 years at baseline and who initiated treatment with eculizumab prior to study entry. Dosing regimen changed solely at the discretion of the treating physician. | 15 |
| Adult Participants with aHUS who were 18 years or older at baseline and who initiated treatment with eculizumab prior to study entry. Dosing regimen changed solely at the discretion of the treating physician. | 52 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Missing | 0 | 1 |
| Overall Study | Other-Additional Information Unavailable | 0 | 11 |
| Overall Study | Participated until study termination | 10 | 26 |
| Overall Study | Physician Decision | 1 | 8 |
| Overall Study | Study Terminated by Sponsor | 3 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Adult | Pediatric | Total |
|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 17.26 | 7.9 years STANDARD_DEVIATION 3.46 | 35.4 years STANDARD_DEVIATION 21.33 |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Caucasian | 44 Participants | 12 Participants | 56 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 34 Participants | 6 Participants | 40 Participants |
| Sex: Female, Male Male | 18 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 52 |
| other Total, other adverse events | 6 / 15 | 31 / 52 |
| serious Total, serious adverse events | 1 / 15 | 14 / 52 |
Outcome results
Primary
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
Population: All enrolled participants. The study was terminated with only 20% of the planned enrollment; because the program lost funding, samples collected 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
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
Population: All enrolled participants. The study was terminated with only 20% of the planned enrollment; because the program lost funding, samples collected 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
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
Population: All enrolled participants. The study was terminated with only 20% of the planned enrollment; because the program lost funding, samples collected 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.