OPTIMIZATION OF MAINTENANCE DOSE WITH ECULIZUMAB ACCORDING TO WEIGHT IN PATIENTS WITH ATYPIC HAEMOLITHIC URINE MUSCLE SYNDROME

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2019-001619-21-ES
• Date of registration: 11/06/2019
• Prospective Registration: Yes
• Primary sponsor: HOSPITAL UNIVERSITARI DE BELLVITGE- IDIBELL
• Public title: OPTIMIZATION OF MAINTENANCE DOSE WITH ECULIZUMAB ACCORDING TO WEIGHT IN PATIENTS WITH ATYPIC HAEMOLITHIC URINE MUSCLE SYNDROME
• Scientific title: PILOT STUDY FOR THE OPTIMITZATION OF THE MAINTENANCE DOSE OF ECULIZUMAB ACCORDING TO THE WEIGHT IN ADULT PATIENTS WITH ATYPIC HEMOLYTIC UREMIC SYNDROME - OPTIMAB
• Date of first enrolment: 07/10/2019
• Target sample size: 10
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001619-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Spain

Contacts

• Name: CAROLINA POLO
• Affiliation: HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL

• Name: CAROLINA POLO
• Affiliation: HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects must be 18 years of age or older and may be of both sexes and of any race.
2. Subjects must have a diagnosis of aHUS documented in their clinical history, be receiving treatment with Eculizumab and be in remission of the disease for at least 12 months.
3. The subjects must present a glomerular filtration according to CKD EPI greater than 30 ml / min at the time of inclusion.
4. Subjects must be willing to give written informed consent for the trial and be able to do so. If a subject can not give their informed consent in writing independently, their legal representative can do so instead.
5. Women of childbearing age (WOCBP) must perform a pregnancy test at the time of inclusion and accept the use of a medically acceptable method of contraception during the selection period and while receiving the medication specified in the protocol. Any woman who is physiologically capable of becoming pregnant, from menarche to postmenopausal, unless she is permanently sterile, is considered a woman of childbearing age. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal condition is defined as the absence of menstruation for 12 months without an alternative medical cause. A high level of follicle stimulating hormone (FSH) in the postmenopausal range can be used to confirm a postmenopausal state in women who do not use hormonal contraceptives or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single measurement of FSH is insufficient.
Only women of childbearing age who sign the contraceptive methods recommended by the Clinical Trial Facilitation Group (CTFG) can participate as highly effective contraceptive methods, that is, with a failure rate of less than 1% per year when used consistently and correct:
• Combined hormonal contraception (containing estrogen and progestogen) associated with the inhibition of ovulation (oral, intravaginal or transdermal).
• Progestin-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable)
• Intrauterine device (IUD)
• Intrauterine hormonal release system (SIU)
• Bilateral tubal occlusion
• Vasectomized partner (provided that the partner is the only sexual partner of the participant in the WOCBP trial and that the vasectomized partner has received a medical evaluation of the surgical success)
• Sexual abstinence (defined as abstaining from sex during the entire period of risk associated with study treatments)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Subjects presenting a glomerular filtration according to CKD EPI less than 30 ml / min.
2. Body weight greater than 120Kg.
3. Pregnant women.
4. Women in breastfeeding period.
5. Institutionalized patients.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ATYPICAL HEMOLYTIC UREMIC SYNDROME
MedDRA version: 20.1 Level: LLT Classification code 10079841 Term: Atypical hemolytic uremic syndrome System Organ Class: 100000004851

Therapeutic area: Not possible to specify

Intervention(s)

Trade Name: SOLIRIS
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1200-

Primary Outcome(s)

Secondary Objective: Analyze the estimated glomerular filtration variation.
Study pharmacokinetic and pharmacodynamic parameters before and after treatment modification.
Study changes in the quality of life of patients.

Primary end point(s): Recurrence rate of the underlying disease (aHUS) due to lack of efficacy of the treatment with Eculizumab.

Main Objective: To explore the safety of dose adjustment of Eculizumab according to body weight in patients with aHUS in remission and in the maintenance phase.

Timepoint(s) of evaluation of this end point: At each study visit (every 15 days during the first 3 months and subsequently quarterly until 12 months from the start of the Study)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At 90, 180 and 360 days of follow-up.

Secondary end point(s): - Safety variables:
• Renal function (serum creatinine and glomerular filtration rate estimated by the CKD-EPI formula), complete blood count and biochemistry with liver profile, 24h urine profile to assess the presence of proteinuria, urinary sediment and fundamental electrolytes (every 15 days the first 3 months and then quarterly).
• Proportion of patients discontinuing treatment with Eculizumab due to adverse effects associated with the drug.

- Pharmacokinetic variables: percentage of patients achieving a Cmin of Eculizumab between 35 and 50 mcg / dL and time until reaching this value of Cmin (by determining the concentration of free Eculizumab in serum).
- Pharmacodynamic variables:
• levels of complement activation (complement activity and membrane attack complex). At baseline and at 90, 180 and 360 days of follow-up.
• Complement system blockade (complement activity, hemolytic capacity CH50 and serum depleted C5). At baseline and at 90, 180 and 360 days of follow-up.

- Quality of Life of the Patient through the questionnaires SF36 and EQ-5D at baseline, at 180 days and at 360 days of follow-up.

Secondary ID(s)

OPTIMAB

Source(s) of Monetary Support

HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL

Ethics review

Status: Approved
Approval date:
Contact: