Clinical Trials Register

Summary
EudraCT Number:	2019-001619-21
Sponsor's Protocol Code Number:	OPTIMAB
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-06-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2019-001619-21

A.3

Full title of the trial

PILOT STUDY FOR THE OPTIMITZATION OF THE MAINTENANCE DOSE OF ECULIZUMAB ACCORDING TO THE WEIGHT IN ADULT PATIENTS WITH ATYPIC HEMOLYTIC UREMIC SYNDROME

ESTUDIO PILOTO PARA LA OPTIMITZACIÓN DE LA DOSIS DE MANTENIMIENTO DE ECULIZUMAB SEGÚN EL PESO EN PACIENTES ADULTOS CON SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

OPTIMIZACIÓN DE LA DOSIS DE MANTENIMIENTO CON ECULIZUMAB SEGÚN EL PESO EN PACIENTES CON SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO

A.3.2

Name or abbreviated title of the trial where available

OPTIMAB

A.4.1

Sponsor's protocol code number

OPTIMAB

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	HOSPITAL UNIVERSITARI DE BELLVITGE- IDIBELL
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL
B.5.2	Functional name of contact point	CAROLINA POLO
B.5.3	Address:
B.5.3.1	Street Address	FEIXA LLARGA, S/N
B.5.3.2	Town/ city	L'HOSPITALET DE LLOBREGAT, BARCELONA
B.5.3.3	Post code	08907
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34932607385
B.5.6	E-mail	cpolo@idibell.cat

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	SOLIRIS
D.2.1.1.2	Name of the Marketing Authorisation holder	Alexion Europe SAS
D.2.1.2	Country which granted the Marketing Authorisation	Spain
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ECULIZUMAB
D.3.9.1	CAS number	219685-50-4
D.3.9.4	EV Substance Code	SUB25187
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ATYPICAL HEMOLYTIC UREMIC SYNDROME

SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO

E.1.1.1

Medical condition in easily understood language

ATYPICAL HEMOLYTIC UREMIC SYNDROME

SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10079841
E.1.2	Term	Atypical hemolytic uremic syndrome
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

Explorar la seguridad del ajuste de dosis de Eculizumab según peso corporal en pacientes con SHUa en remisión y en fase de mantenimiento.

E.2.2

Secondary objectives of the trial

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.

Analizar la variación del filtrado glomerular estimado.
Estudiar parámetros farmacocinéticos y farmacodinámicos antes y después de la modificación del tratamiento.
Estudiar los cambios en la calidad de vida de los pacientes.

E.2.3

Trial contains a sub-study

E.3

Principal 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)

1. Los sujetos deberán tener 18 años o más y podrán ser de ambos sexos y de cualquier raza.
2. Los sujetos deberán tener un diagnóstico de SHUa documentado en su historia clínica, estar recibiendo tratamiento con Eculizumab y estar en remisión de la enfermedad desde al menos 12 meses.
3. Los sujetos deberán presentar un Filtrado glomerular según CKD EPI superior a 30 ml/min en el momento de la inclusión.
4. Los sujetos deberán estar dispuestos a otorgar su consentimiento informado por escrito para el ensayo y ser capaces de hacerlo. Si un sujeto no puede otorgar su consentimiento informado por escrito de forma independiente, podrá hacerlo su representante legal en su lugar.
5. Las mujeres en edad fértil (WOCBP) deberán realizar un test de embarazo en el momento de la inclusión y aceptar el uso de un método anticonceptivo médicamente aceptable durante el periodo de selección y mientras reciban la medicación especificada en el protocolo. Se considera mujer en edad fértil toda aquella mujer fisiológicamente capaz de quedarse embarazada, desde la menarquia hasta convertirse en posmenopáusica, a menos que sea permanente estéril. Los métodos de esterilización permanentes incluyen histerectomía, salpingectomía bilateral y ooforectomía bilateral. Un estado posmenopáusico se define como ausencia de menstruación durante 12 meses sin una causa médica alternativa. Un nivel alto de hormona estimulante del folículo (FSH) en el rango posmenopáusico puede ser utilizado para confirmar un estado postmenopáusico en mujeres que no usan anticonceptivos hormonales o terapia de reemplazo hormonal. Sin embargo, en ausencia de 12 meses de amenorrea, una sola medición de FSH es insuficiente.
Sólo podrán participar mujeres en edad fértil que signa los métodos anticonceptivos recomendados por el Clinical Trial Facilitation Group (CTFG) como métodos anticonceptivos altamente efectivos, es decir, con una tasa de fracaso de menos del 1% por año cuando se usa de manera consistente y correcta:
• Anticoncepción hormonal combinada (que contiene estrógeno y progestágeno) asociada a la inhibición de la ovulación (oral, intravaginal o transdérmica).
• Anticoncepción hormonal de progestágeno solo asociada con la inhibición de la ovulación (oral, inyectable o implantable)
• Dispositivo intrauterino (DIU)
• Sistema de liberación hormonal intrauterino (SIU)
• Oclusión tubárica bilateral
• Pareja vasectomizada (siempre que la pareja sea la única pareja sexual del participante en el ensayo WOCBP y que la pareja vasectomizada ha recibido una evaluación médica del éxito quirúrgico)
• Abstinencia sexual (definida como abstenerse de tener relaciones sexuales durante todo el periodo de riesgo asociado a los tratamientos de estudio)

E.4

Principal 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.

1. Sujetos que presenten un Filtrado glomerular según CKD EPI inferior a 30 ml/min.
2. Peso corporal superior a 120Kg.
3. Mujeres embarazadas.
4. Mujeres en periodo de lactancia.
5. Pacientes institucionalizados.

E.5 End points

E.5.1

Primary end point(s)

Recurrence rate of the underlying disease (aHUS) due to lack of efficacy of the treatment with Eculizumab.

Tasa de recurrencia de la enfermedad de base (SHUa) por falta de eficacia del tratamiento con Eculizumab.

E.5.1.1

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)

En cada visita del estudio (cada 15 días durante los 3 primeros meses y posteriormente trimestrales hasta los 12 meses desde el inicio del Estudio)

E.5.2

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.

- Variables de seguridad:
• Función renal (creatinina sérica y filtrado glomerular estimado por fórmula de CKD-EPI), hemograma completo y bioquímica con perfil hepático, perfil de orina de 24h para valorar la presencia de proteinuria, sedimento urinario y electrolitos fundamentales (cada 15 días los 3 primeros meses y posteriormente de forma trimestral).
• Proporción de pacientes que discontinúan el tratamiento con Eculizumab debido a efectos adversos asociados al fármaco.

- Variables farmacocinéticas: porcentaje de pacientes que alcanzan una Cmin de Eculizumab entre 35 y 50 mcg/dL y tiempo hasta alcanzar este valor de Cmin (mediante la determinación de la concentración de Eculizumab libre en suero).
- Variables Farmacodiámicas:
• niveles de activación del complemento (actividad del complemento y del complejo de ataque de la membrana). En el punto basal y a los 90, 180 y 360 días de seguimiento.
• bloqueo del sistema de complemento (actividad del complemento, capacidad hemolítica CH50 y suero deplecionado C5). En el punto basal y a los 90, 180 y 360 días de seguimiento.

- Calidad de Vida del Paciente mediante los cuestionarios SF36 y EQ-5D en el punto basal, a los 180 días y a los 360 días de seguimiento.

E.5.2.1

Timepoint(s) of evaluation of this end point

At 90, 180 and 360 days of follow-up.

A los 90, 180 y 360 días de seguimiento.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

NONE

NINGUNO

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-26

P. End of Trial
P.	End of Trial Status	Ongoing

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