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

Phase 2

• Conditions: Atypical hemolytic uremic syndrome; Urological and Genital Diseases; Haemolytic-uraemic syndrome

• Registration Number: ISRCTN17503205
• Lead Sponsor: The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Brief Summary

2022 Protocol article in https://pubmed.ncbi.nlm.nih.gov/36123058/ (added 20/09/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-20
• Last Update Posted: 9 January 2023
• Study Completion: 2023-11-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

All patients must fulfil the following criteria in order to be eligible for the trial:
1. Age =2+ years of age
2. On Eculizumab treatment for at least 6 months
3. In remission with no evidence of ongoing microangiopathic haemolytic anaemia (MAHA) activity at screening defined by:
3.1. Platelet count > lower limit of normal as determined by local reference range
3.2. Lactate Dehydrogenase (LDH) 4. Normal renal function or Chronic Kidney Disease (CKD) stages 1-3
5. Absence of decline of renal function confirmed by review of available assessments of renal function for the preceding 6 months by the Chief Investigator and clinical members of the Trial Management Group (TMG)
6. Willing to attend for safety monitoring assessments
7. Willing to travel only to countries that can supply Eculizumab (to be confirmed with co-ordinating centre prior to travel).

The following criteria must be met by those only wishing to be enrolled in the withdrawal component of the trial:
8. Able to perform or parent/guardian to perform and record self-monitoring urinalysis
9. Sexually active female patients must have a negative pregnancy test at screening and be using an effective contraception for the duration of the study (implant, injectable [combined hormone], intrauterine device, intrauterine system, male sterilisation,
injectable (single hormone), combined oral, progesterone only)
OR
10. Fulfil one of the following criteria:
10.1. Be postmenopausal
10.2. Have undergone surgical sterilisation

Exclusion Criteria

1. 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
2. Loss of a previous transplant kidney to recurrent aHUS
3. Transplant recipient with a pathogenic mutation in C3, CFH or CFB
4. Current or planned pregnancy
5. Unable to give informed consent or assent, or unable to obtain parent/guardian consent if under 16 years of age
6. Unable to comply with monitoring protocol
7. Current participation in another clinical trial
8. Haematuria rating of 3+
9. Severe, uncontrolled hypertension (systolic blood pressure > 160 mmHg) that is likely to induce at TMA

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Number of patients with a Thrombotic Microangiopathy (TMA) related Serious Adverse Event (SAE) defined as any of the following:<br> 1. Irreversible (>3 months) reduction in estimated glomerular filtration rate (eGFR) by =20%, not attributable to another cause<br> 2. An episode of AKI attributed to a TMA that requires renal replacement therapy<br> 3. A non-renal manifestation of a TMA that require hospitalisation, cause irreversible organ damage or death<br> Timepoint(s): Only if/when a patient relapses<br>