Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring (EspacECU)

NCT04859608 | Completed Phase 3 DMC

• 1 other identifier: DR200088-EspacECU
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 18

Brief Summary

Eculizumab is an anti-C5 monoclonal antibody approved for rare diseases including atypical haemolytic-uraemic syndrome. The maintenance phase dosing regimen is identical for all adult patients but several studies have shown a high interindividual kinetics variability. A tailored administration of eculizumab based on therapeutic drug monitoring will be compared with real-life administration in adults suffering from an atypical haemolytic uraemic syndrome. The objective is to improve efficiency of eculizumab administration.

Conditions

Hemolytic-Uremic Syndrome, Atypical

Keywords

Hemolytic-Uremic Syndrome; Kidney Diseases; Thrombotic Microangiopathies; Therapeutic drug monitoring; Eculizumab tailoring; Cost-utility analysis; Markov model

Outcome Measures

Primary Outcomes (1)

• Incremental Cost-Utility Ratio (ICUR) at 18 months of a personalized spacing of eculizumab infusions compared to the usual administration scheme without personalization, from the French health insurance perspective.

  The ICUR will express the incremental cost per QALY (Quality-adjusted Life Years) gained over a 18-month time horizon. QALYs will be estimated from patient responses to the EQ-5D-5L instrument (EuroQol group - 5 Dimensions - 5 levels). Costs related to hospital care resources (medicalized information system program), transports (patient diary), eculizumab concentration dosing (cost estimation) will be estimated from the French Health Insurance perspective. Cost and QALY estimates will be used to estimate the within-trial ICUR.

  18 months

Secondary Outcomes (4)

• Incremental Cost-Utility Ratio at 5 years (incremental cost per QALY gained) of a personalized spacing of the eculizumab infusions compared to the usual administration scheme without personalization, estimated from a Markov model.

  5 years

• Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions

  per year and over a 5-year period

• Quality of life measured over a 18-month period using different specific scales (KDQoL-SF, ReTransQoL-Version 2) dedicated to patients with renal disease

  at baseline, 3, 6, 9, 12, 15 and 18 months.

• Determining the factors of intra- and inter- individual variability of eculizumab concentrations.

  5 years

Study Arms (2)

Therapeutic drug monitoring

EXPERIMENTAL

Tailored dosing schedule for eculizumab based on therapeutic drug monitoring

Drug: Spacing of Eculizumab infusions

Control

NO INTERVENTION

Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm.

Interventions

Spacing of Eculizumab infusions DRUG

Personalized spacing of eculizumab infusions using a pharmacokinetic population model to estimate eculizumab concentration ( a one-week spacing of eculizumab infusion will be decide if predicted eculizumab concentration in the event of spacing is \> 150 mg/L). Spacing of infusion can be decided every 3 months.

Therapeutic drug monitoring

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with an atypical Hemolytic and Uremic Syndrome defined by at least 2 of the following parameters:
• Thrombopenia (platelet count \< 150 G/L)
• Mechanical lytic anemia (Hb \< 10 g/L, Lactate dehydrogenase \> upper limit of normal, undetectable haptoglobin, presence of schistocytes on blood smear)
• Acute renal failure
• Eculizumab treatment
• Without project of withdrawal in the next 18 months
• Started since at least 6 months
• Administrated with an unchanged administration schedule since at least 3 months (initial episode or relapse)
• Atypical Hemolytic and Uremic Syndrome in remission
• Patients who give informed consent.

You may not qualify if:

• Patients on dialysis.
• Women treated starting or planning a pregnancy.
• Patients suffering from a typical or secondary microangiopathic hemolytic anemia (drugs, malignancies, autoimmune disease...)
• Patients under protection of a judicial authority

Sponsors & Collaborators

• University Hospital, Tours: lead
• Centre Hospitalier Universitaire, Amiens: collaborator
• University Hospital, Angers: collaborator
• Centre Hospitalier Universitaire de Besancon: collaborator
• University Hospital, Caen: collaborator
• Centre Hospitalier of Chartres: collaborator
• Nantes University Hospital: collaborator
• University of Nancy: collaborator
• Poitiers University Hospital: collaborator
• Rennes University Hospital: collaborator
• University Hospital, Rouen: collaborator
• University Hospital, Strasbourg, France: collaborator
• Centre Hospitalier Universitaire de Nice: collaborator
• Hôpital Necker-Enfants Malades: collaborator
• Tenon Hospital, Paris: collaborator
• University Hospital, Lille: collaborator
• Reims University hospital: collaborator
• University Hospital, Clermont-Ferrand: collaborator
• Assistance Publique Hopitaux De Marseille: collaborator
• Hospices Civils de Lyon: collaborator

Study Sites (18)

CHU Amiens Picardie

Amiens, France

Location

CHU d'Angers

Angers, France

Location

Hôpital Tenon

APHP Tenon, France

Location

CHU Besançon

Besançon, France

Location

Hôpital de la Côte de Nacre

Caen, France

Location

Hôpital Louis Pasteur

Chartres, France

Location

Hôpital Gabriel Montpied

Clermont-Ferrand, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Hopital de la conception

Marseille, France

Location

Hôpitaux de Brabois

Nancy, France

Location

Hotel Dieu

Nantes, France

Location

Hopital Necker

Necker, France

Location

Hopital Pasteur 2

Nice, France

Location

Hôpital de la Milétrie

Poitiers, France

Location

Hôpital Maison Blanche

Reims, France

Location

Hôpital Pontchaillou

Rennes, France

Location

Hôpital de Bois-Guillaume

Rouen, France

Location

Nouvel Hôpital Civil

Strasbourg, France

Location

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome; Hemolytic-Uremic Syndrome; Kidney Diseases; Thrombotic Microangiopathies

Condition Hierarchy (Ancestors)

Uremia; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized (2:1) controlled study, open-label, with Markov modeling.

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: April 26, 2021
• Study Start: October 20, 2021
• Primary Completion: June 16, 2022
• Study Completion: December 28, 2023
• Last Updated: March 25, 2025

Record last verified: 2025-03

Locations

FR (18)