Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS

Phase 4

Completed

• Conditions: Atypical Hemolytic Uremic Syndrome
• Interventions: Drug: eculizumab

• Registration Number: NCT02574403
• Lead Sponsor: Nantes University Hospital

Brief Summary

Atypical hemolytic syndrome (aHUS) is a severe renal disease affecting children and adults. It is characterized by the occlusion of intrarenal vessels due to the presence of platelet/fibrin thrombi, and leads to end-stage renal disease in up to 2/3 of patients. The discovery of complement alternative pathway as a major risk factor for aHUS has led to the design of a disease-specific treatment, the anti-C5 monoclonal antibody, eculizumab. Complement inhibition using eculizumab has clearly improved the renal outcome of aHUS patients with a dramatic decrease in the risk of end-stage renal disease. However, the optimal duration of eculizumab therapy is still debated. The present study aims to assess the feasibility and safety of the discontinuation of eculizumab treatment in children and adults with aHUS.

Detailed Description

A visit (physical examination; blood pressure measurement) will be performed every month for 3 months, and every 3 months for 21 months.

Blood (serum creatinine, platelet count, hemoglobin, LDH, haptoglobin) and urine (proteinuria/creatininuria ratio and microscopic hematuria) tests will be performed every 2 weeks from inclusion to M6 and subsequently every month starting M7 Urine dipstick (for albuminuria and microscopic hematuria) will be performed by the patients at home at least twice a week.

Markers of complement activation and biomarkers of endothelial cells activation and immune cells activation will be assessed at baseline, M1, M3, M6, M9, M12, M18 and M24.

Study Timeline

• Study First Submitted: 2015-10-05
• Study First Submitted QC: 2015-10-09
• Study First Posted: 2015-10-12
• Study Start: 2015-11
• Status Verified: 2019-12
• Primary Completion: 2019-12-03
• Study Completion: 2019-12-03
• Last Update Submitted: 2019-12-05
• Last Update Posted: 2019-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

1. Children and adults under eculizumab treatment for aHUS (initial episode or relapse) defined by at least two of the following: thrombocytopenia (platelet count < 150 G/L), mechanical hemolytical anaemia (Hb < 10 g:dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schizocytes on blood smear), acute kidney injury (serum creatinine and/or proteinuria/creatininuria > upper limit of normal for age or an increase > 15% compared to baseline levels )
2. Patients not requiring dialysis.
3. Adults: HUS remission and normal or stabilized renal function under eculizumab treatment since at least 6 months (3 months in patients with MCP mutations)
4. Children: age > 3 years at eculizumab withdrawal; HUS remission and normal renal function under eculizumab treatment since at least 3 months in children with isolated MCP mutation, at least 6 months in children with complement mutation other than MCP.

Exclusion Criteria

1. Patients on dialysis.
2. Women treated with eculizumab starting or planning a pregnancy. Pregnancy including the post-partum period is high-risk periods for the occurrence of aHUS.
3. Patients who did not give informed consent.
4. Patients under protection of a judicial authority

Patients can be enrolled in the study within ten weeks after Eculizumab stop.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
without eculizumab	eculizumab	-

Primary Outcome Measures

Name	Time	Method
The incidence of aHUS relapse during 2 years of follow-up after eculizumab discontinuation	24 months	aHUS relapse will be defined by the coexistence of at least two of the following: * thrombocytopenia (platelet count \< 150 G/L),; * mechanical hemolytical anaemia (Hb \< 10 g/dl, LDH \> upper limit of normal, undetectable haptoglobin, presence of schizocytes on blood smear),; * acute kidney injury (serum creatinine and/or proteinuria/creatininuria \> upper limit of normal for age or an increase \> 15% compared to baseline levels ),; * features of thrombotic microangiopathy (glomerular and/or arteriolar thrombi, doubles contours, endothelial cells detachment) in a kidney biopsy, if performed.

Trial Locations

Locations (22)

CHU Amiens; 🇫🇷 Amiens, France

CHU Caen; 🇫🇷 Caen, France

CHU Bordeaux; 🇫🇷 Bordeaux, France

CH Dijon; 🇫🇷 Dijon, France

CHRU Lille; 🇫🇷 Lille, France

AP-HM; 🇫🇷 Marseille, France

CHU lyon; 🇫🇷 Lyon, France

CH Metz Thionville; 🇫🇷 Metz, France

CHU Nantes; 🇫🇷 Nantes, France

CHU Montpellier; 🇫🇷 Montpellier, France

CHU Nice; 🇫🇷 NIce, France

Hopital Tenon; 🇫🇷 Paris, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

Hopital Necker; 🇫🇷 Paris, France

CHU Rouen; 🇫🇷 Rouen, France

CH Alpes Léman; 🇫🇷 Sallanches, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

Hopital FOCH; 🇫🇷 Suresnes, France

CHU toulouse; 🇫🇷 Toulouse, France

CH métropole Savoie; 🇫🇷 Chambéry, France

Ch Le Mans; 🇫🇷 Le Mans, France

BICHAT; 🇫🇷 Paris, France