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

Sponsor

University Hospital, Tours (Other)

Overall Status

Recruiting

CT.gov ID

NCT04859608

Collaborator

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

Enrollment

Locations

Arms

Anticipated Duration (Months)

4.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hemolytic-Uremic Syndrome, Atypical	Drug: Spacing of Eculizumab infusions	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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. [18 months]
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.

Secondary Outcome Measures

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]
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.
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]
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).
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.]
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.
Determining the factors of intra- and inter- individual variability of eculizumab concentrations. [5 years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country
1	CHU Amiens Picardie	Amiens	France
2	CHU d'Angers	Angers	France
3	Hôpital Tenon	APHP Tenon	France
4	CHU Besançon	Besançon	France
5	Hôpital de la Côte de Nacre	Caen	France
6	Hôpital Louis Pasteur	Chartres	France
7	Hôpital Gabriel Montpied	Clermont-Ferrand	France
8	Hospices Civils de Lyon	Lyon	France
9	Hopital de la conception	Marseille	France
10	Hôpitaux de Brabois	Nancy	France
11	Hotel Dieu	Nantes	France
12	Hopital Necker	Necker	France
13	Hopital Pasteur 2	Nice	France
14	Hôpital de la Milétrie	Poitiers	France
15	Hôpital Maison Blanche	Reims	France
16	Hôpital Pontchaillou	Rennes	France
17	Hôpital de Bois-Guillaume	Rouen	France
18	Nouvel Hôpital Civil	Strasbourg	France