Stopping Eculizumab Treatment Safely in atypical Haemolytic Uraemic Syndrome (SETS aHUS)

Conditions

Atypical Haemolytic Uraemic Syndrome (aHUS)

Neil Sheerin, Sally Johnson, Michal Malina, Emma Montgomery, Edwin Wong et al. (12 authors)

Nephrology Dialysis Transplantation2025-10-01

Eculizumab withdrawal and monitoring in atypical haemolytic uraemic syndrome (SETS aHUS): a multicentre, open label, prospective, single arm trial.

Bryant A, Lecouturier J, Orozco-Leal G, Brocklebank V, Carnell S, Chadwick T, Dunn S, Johnson S, Kavanagh D, Kennedy C, Malina M, Montgomery E, Muirhead C, Oluboyede Y, Vale L, Weetman C, Wong E, Sheerin NS, SETS aHUS Consortium.

2025-08-07

10.1016/j.lanepe.2025.101392

Interventions

Trade Name: Solaris Product Name: Solaris Pharmaceutical Form: Infusion INN or Proposed INN: Eculizumab CAS Number: 219685-50-4

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Age =2+ years of age • On Eculizumab treatment for at least 6 months • In remission with no evidence of ongoing microangiopathic haemolytic anaemia (MAHA) activity at screening defined by: - Platelet count > lower limit of normal as determined by local reference range - LDH =65 years) no F.1.3.1 Number of subjects for this age range 2

Exclusion criteria

Exclusion criteria: • Severe non-renal disease manifestations at initial presentation with aHUS, which in the opinion of the Chief Investigator and/or the clinical members of the TMG makes the risk of treatment withdrawal unacceptable. • Loss of a previous transplant kidney to recurrent aHUS • Transplant recipient with a pathogenic mutation in C3, CFH or CFB • Current or planned pregnancy • Unable to give informed consent or assent, or unable to obtain parent/guardian consent if under 16 years of age • Unable to comply with monitoring protocol • Current participation in another clinical trial • Haematuria rating of 3+ • Severe, uncontrolled hypertension (systolic blood pressure >160 mmHg) that is likely to induce at TMA. • Current participation in another clinical trial (not including participation in ahus registries)

Design outcomes

Primary

Measure	Time frame
Main Objective: The principle clinical research objective is to determine the safety of Eculizumab withdrawal in patients with aHUS. ; Secondary Objective: 1. Measure the effectiveness of a monitoring protocol to detect disease relapse following withdrawal of Eculizumab. 2. Describe the relapse rate after withdrawal of Eculizumab. 3. Estimate the proportion of patients, currently on long-term treatment with Eculizumab, who can be maintained off treatment. 4. Describe the period from withdrawal to relapse in those patients who restart treatment. 5. Measure the change in estimated GFR (calculated by the CKD-EPI or modified Schwartz equations) over the course of the study. 6. Identify important clinical and laboratory indicators of imminent relapse. Heath Economic Objectives 7. To assess the costs and health outcomes (measured in terms of adverse events and quality-adjusted life years (QALYs)) for patients on standard care (not withdrawing from Eculizumab treatment) over the two-year trial duration. 8. To assess the costs and health outcomes for patients fully, or partially, withdrawing from Eculizumab treatment, and on a policy of protoco ; Primary end point(s): Number of patients with a Thrombotic Microangiopathy (TMA) related Serious Adverse Event (SAE) defined as any of the following: • Irreversible (>3 months) reduction in estimated glomerular filtration rate (eGFR) by =20%, not attributable to another cause • An episode of AKI attributed to a TMA that requires renal replacement therapy • A non-renal manifestation of a TMA that require hospitalisation, cause irreversible organ damage or death. ;Timepoint(s) of evaluation of this end point: 24 months after the patient has their baseline visit.	—

Measure

Time frame

Main Objective: The principle clinical research objective is to determine the safety of Eculizumab withdrawal in patients with aHUS. ; Secondary Objective: 1. Measure the effectiveness of a monitoring protocol to detect disease relapse following withdrawal of Eculizumab. 2. Describe the relapse rate after withdrawal of Eculizumab. 3. Estimate the proportion of patients, currently on long-term treatment with Eculizumab, who can be maintained off treatment. 4. Describe the period from withdrawal to relapse in those patients who restart treatment. 5. Measure the change in estimated GFR (calculated by the CKD-EPI or modified Schwartz equations) over the course of the study. 6. Identify important clinical and laboratory indicators of imminent relapse. Heath Economic Objectives 7. To assess the costs and health outcomes (measured in terms of adverse events and quality-adjusted life years (QALYs)) for patients on standard care (not withdrawing from Eculizumab treatment) over the two-year trial duration. 8. To assess the costs and health outcomes for patients fully, or partially, withdrawing from Eculizumab treatment, and on a policy of protoco ; Primary end point(s): Number of patients with a Thrombotic Microangiopathy (TMA) related Serious Adverse Event (SAE) defined as any of the following: • Irreversible (>3 months) reduction in estimated glomerular filtration rate (eGFR) by =20%, not attributable to another cause • An episode of AKI attributed to a TMA that requires renal replacement therapy • A non-renal manifestation of a TMA that require hospitalisation, cause irreversible organ damage or death. ;Timepoint(s) of evaluation of this end point: 24 months after the patient has their baseline visit.

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: 24 months after the patient has their baseline visit. ; Secondary end point(s): 1. The effectiveness of a monitoring protocol to detect disease relapse following withdrawal of Eculizumab assessed by: i. The proportion of patients who relapse and restart Eculizumab without the development of a TMA-related SAE (section 3.3). ii. The time from the first clinical feature (symptom, positive urinalysis or laboratory result) of a relapse of TMA and the re-introduction of Eculizumab treatment. 2. The relapse rate after withdrawal of Eculizumab as determined by the proportion of patients who relapse after Eculizumab is withdrawn. 3. Estimate of the proportion of patients, currently on long-term treatment with Eculizumab, who can be maintained off treatment. 4. Description of the period from withdrawal to relapse in those patients who restart treatment measured from baseline (day 0) to day of re-introduction of treatment or end of the study. 5. The change in estimated GFR as calculated by the CKD-EPI or modified Schwartz equations over the course of the study from baseline (day 0) to end of the study. 6. Identification of important clinical and laboratory indicators of imminent relapse by review of reported symptoms, physical signs, urinalysis and laboratory results prior to the diagnosis of a relapse. Heath Economic Outcome Measures 7. Cumulative costs to the NHS and participants, and determinants of costs, over the 24-month follow-up period. 8. QALYs estimated from responses to the EQ-5D-5L, and SF-36, completed at pre-determined time points, and determinants of QALYs/utilities, over the 24-month follow-up period. 9. Model-based estimate of the costs and health consequences, with results presented in terms of cost per QALY gai	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: 24 months after the patient has their baseline visit. ; Secondary end point(s): 1. The effectiveness of a monitoring protocol to detect disease relapse following withdrawal of Eculizumab assessed by: i. The proportion of patients who relapse and restart Eculizumab without the development of a TMA-related SAE (section 3.3). ii. The time from the first clinical feature (symptom, positive urinalysis or laboratory result) of a relapse of TMA and the re-introduction of Eculizumab treatment. 2. The relapse rate after withdrawal of Eculizumab as determined by the proportion of patients who relapse after Eculizumab is withdrawn. 3. Estimate of the proportion of patients, currently on long-term treatment with Eculizumab, who can be maintained off treatment. 4. Description of the period from withdrawal to relapse in those patients who restart treatment measured from baseline (day 0) to day of re-introduction of treatment or end of the study. 5. The change in estimated GFR as calculated by the CKD-EPI or modified Schwartz equations over the course of the study from baseline (day 0) to end of the study. 6. Identification of important clinical and laboratory indicators of imminent relapse by review of reported symptoms, physical signs, urinalysis and laboratory results prior to the diagnosis of a relapse. Heath Economic Outcome Measures 7. Cumulative costs to the NHS and participants, and determinants of costs, over the 24-month follow-up period. 8. QALYs estimated from responses to the EQ-5D-5L, and SF-36, completed at pre-determined time points, and determinants of QALYs/utilities, over the 24-month follow-up period. 9. Model-based estimate of the costs and health consequences, with results presented in terms of cost per QALY gai

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Countries

United Kingdom

Contacts

Public ContactSarah Dunn

Newcastle Clinical Trial Unit

sarah.dunn2@ncl.ac.uk01912082521

Outcome results

None listed