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

Personalized Spacing of Eculizumab Infusions Based on Therapeutic Pharmacological Monitoring: Prospective Health-economic Evaluation in Patients in Remission With Atypical Hemolytic Uraemic Syndrome Requiring Long-term Treatment.

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.

Study Overview

• Status: Completed
• Conditions: Hemolytic-Uremic Syndrome, Atypical
• Intervention / Treatment: Drug: Spacing of Eculizumab infusions

Detailed Description

Eculizumab is a very expensive drug (450 000 euros per year per patient). According to the usual administration scheme, the eculizumab is administrated by intravenous infusion, every 14 or 21 days in hospital. Studies have shown the possibility of extending the administration intervals in patients with a high concentration of eculizumab.

A personalized spacing of eculizumab infusions, based on a therapeutic drug monitoring, is expected to improve the patient's quality of life and lead to substantial savings.

For these reasons, the objective of this study is to explore the efficiency of a personalized spacing of eculizumab infusions compared to the usual administration scheme (without personalization) from the French health Insurance perspective. The efficiency will be assessed by estimating the incremental cost per QALY (Quality-Adjusted Life Year) gained at 18 months (duration of follow-up in the clinical trial) and at 5 years thanks to a Markov model.

The total duration of the study is 24 months (6 months of enrolment and 18 months of follow-up).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • APHP Tenon, France
    • Hôpital Tenon
  • Amiens, France
    • CHU Amiens Picardie
  • Angers, France
    • CHU d'Angers
  • Besançon, France
    • CHU Besançon
  • Caen, France
    • Hôpital de la Côte de Nacre
  • Chartres, France
    • Hopital Louis Pasteur
  • Clermont-Ferrand, France
    • Hopital Gabriel Montpied
  • Lyon, France
    • Hospices Civils de Lyon
  • Marseille, France
    • Hôpital de la Conception
  • Nancy, France
    • Hopitaux de Brabois
  • Nantes, France
    • Hotel Dieu
  • Necker, France
    • Hopital Necker
  • Nice, France
    • Hopital Pasteur 2
  • Poitiers, France
    • Hopital de la Milétrie
  • Reims, France
    • Hopital Maison Blanche
  • Rennes, France
    • Hôpital Pontchaillou
  • Rouen, France
    • Hôpital de Bois-Guillaume
  • Strasbourg, France
    • Nouvel Hôpital Civil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. 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)
3. Atypical Hemolytic and Uremic Syndrome in remission
4. Patients who give informed consent.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapeutic drug monitoring; Tailored dosing schedule for eculizumab based on therapeutic drug monitoring	Drug: Spacing of Eculizumab infusions; 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.
No Intervention: Control; Initial eculizumab schedule is continued (real-life arm). No eculizumab dosages are performed in this arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	A Markov model will represent the patient's clinical progression across different health states over a 5-year period. Markov modelling will use the within-trial data to estimate the transition probabilities, the state cost and utility values.	5 years
Financial impact per year and over a 5-year period of a personalized spacing of eculizumab infusions	The financial impact of spreading the strategy of personalized spacing of eculizumab infusions, in patients in remission with atypical hemolytic uraemic syndrome requiring long-term treatment, will be estimated per year and over a 5-year period, from the French Health Insurance (using a budget impact model).	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	KDQoL-SF (Kidney Disease and Quality of Life™ Short Form) survey is a kidney-disease-specific quality of life instrument that assesses four domains : health, kidney disease, effects of kidney disease on daily life, satisfaction with care. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. RTQ-V2 (ReTransQoL-Version 2) survey is a specific quality of life instrument for renal transplant recipients. It comprises of 32 items describing five domains: Physical Health, Social Functioning, Medical Care, Treatment and Fear of Losing Graft. Scores for each dimension are reported within the range 0-100, higher scores indicating better health- related quality of life. KDQoL-SF survey will be used for all patients, and RTQ-V2 survey for kidney transplant patients only. The quality of life will be measured every three months.	at baseline, 3, 6, 9, 12, 15 and 18 months.
Determining the factors of intra- and inter- individual variability of eculizumab concentrations.	A study will be performed to determine whether biological and genetic (complement genetic variants reported as cause of HUS) parameters influence trough concentrations of eculizumab	5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Actual): June 16, 2022
• Study Completion (Actual): December 28, 2023

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Therapeutic drug monitoring; Kidney Diseases; Hemolytic-Uremic Syndrome; Thrombotic Microangiopathies; Eculizumab tailoring; Cost-utility analysis; Markov model
• Additional Relevant MeSH Terms: Urogenital Diseases; Cytopenia; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease; Hematologic Diseases; Anemia, Hemolytic; Anemia; Blood Platelet Disorders; Thrombotic Microangiopathies; Thrombocytopenia; Uremia; Syndrome; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Azotemia; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: DR200088-EspacECU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No