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

Regional University Hospital Center (CHRU)

Status and phase: Completed; Phase 3

Conditions: Hemolytic-Uremic Syndrome, Atypical

Treatments: Drug: Spacing of Eculizumab infusions

Study type: Interventional

Funder types: Other

Identifiers

NCT04859608

DR200088-EspacECU

Details and patient eligibility

About

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.

Full 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).

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Therapeutic drug monitoring

Experimental group

Description:

Tailored dosing schedule for eculizumab based on therapeutic drug monitoring

Treatment:

Drug: Spacing of Eculizumab infusions

Control

No Intervention group

Description:

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