Clinical Trials Register

Summary
EudraCT Number:	2017-001746-10
Sponsor's Protocol Code Number:	CSEG101A2301
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:	2019-07-05
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

2017-001746-10

A.3

Full title of the trial

A phase III, Multicenter, Randomized, Double-blind Study to Assess Efficacy and Safety of Two Doses of
Crizanlizumab versus placebo, with or without Hydroxyurea/ Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients with Vaso-Occlusive Crises (STAND)

Estudio de fase III, multicéntrico, aleatorizado y doble ciego para evaluar la eficacia y seguridad de dos dosis de crizanlizumab frente a placebo, con o sin hidroxiurea/hidroxicarbamida, en pacientes adolescentes y adultos con enfermedad de células falciformes con crisis vaso-oclusivas (STAND).

A.3.1

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

Study of two doses of crizanlizumab versus placebo in adolescent and adult sickle cell disease patients

Estudio de dos dosis de crizanlizumab frente a placebo en pacientes adolescentes y adultos con enfermedad de células falciformes.

A.3.2

Name or abbreviated title of the trial where available

STAND

A.4.1

Sponsor's protocol code number

CSEG101A2301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03814746

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	Novartis Farmacéutica, S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Farmacéutica, S.A.
B.5.2	Functional name of contact point	Trial Monitoring Organization (TMo)
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía de les Corts Catalanes, 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	34 90 0353036
B.5.5	Fax number	34 93 2479903
B.5.6	E-mail	eecc.novartis@novartis.com

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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/12/1034
D.3 Description of the IMP
D.3.1	Product name	crizanlizumab
D.3.2	Product code	SEG101
D.3.4	Pharmaceutical form	Concentrate for 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	CRIZANLIZUMAB
D.3.9.2	Current sponsor code	SEG101
D.3.9.4	EV Substance Code	SUB188615
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Concentrate for solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sickle Cell Disease with vaso-occlusive crisis

Enfermedad de células falciformes con crisis vaso-oclusivas

E.1.1.1

Medical condition in easily understood language

Sickle Cell Disease

Enfermedad de células falciformes

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10040644
E.1.2	Term	Sickle cell disease
E.1.2	System Organ Class	100000004850

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	10002077
E.1.2	Term	Anaemia sickle cell
E.1.2	System Organ Class	100000004850

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 compare the efficacy of 7.5 mg/kg of
crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care
- To compare the efficacy of 5.0 mg/kg of
crizanlizumab versus placebo on the annualized rate of VOC leading to healthcare visit, in addition to standard of care

-Comparar la eficacia de 7,5 mg/kg de crizanlizumab frente a placebo, además del tratamiento de referencia, en la tasa anual de CVO que deriven en visita clínica.
-Comparar la eficacia de 5 mg/kg de crizanlizumab frente a placebo, además del tratamiento de referencia, en la tasa anual de CVO que deriven en visita clínica

E.2.2

Secondary objectives of the trial

Key secondary:
- To compare the efficacy of 7.5 mg/kg vs placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit)
- To compare the efficacy of 5.0 mg/kg vs placebo on the annualized rate of all VOC (managed at home + leading to healthcare visit)

- To assess the time to first and second VOC leading to healthcare visit in each group
- To assess the number of days with VOC leading to healthcare visit in each group
- To assess rate of subjects free from VOC leading to healthcare visit in each group
- Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) in each group vs placebo
- To assess SCD-related renal damage in each group
- To characterize PK profile of crizanlizumab at 5.0 and 7.5 mg/kg
- To characterize PD (P-selectin inhibition) of
crizanlizumab at 5.0 and 7.5 mg/kg
- To assess efficacy, safety and immunogenicity of crizanlizumab over the study period (treatment of 5 y + 105 d follow-up)

-Comparar la eficacia de 7,5 mg/kg frente a placebo en la tasa anual de todas las CVO (tratadas en el domicilio + que deriven en visita clínica).
-Comparar la eficacia de 5 mg/kg frente a placebo en la tasa anual de todas las CVO (tratadas en el domicilio + que deriven en visita clínica).
-Evaluar el tiempo hasta la primera y segunda CVO que deriven en visita clínica en cada grupo.
-Evaluar la tasa de sujetos sin CVO que deriven en visita clínica en cada grupo.
-Evaluar el número de días con CVO que deriven en visita clínica en cada grupo.
-Uso de recursos sanitarios (visitas al centro, urgencias [URG.] y hospitalizaciones) en cada grupo.
-Evaluar el daño renal relacionado con ECF en cada grupo.
-Caracterizar el PK de crizanlizumab en dosis de 5 y 7,5 mg/kg.
-Caracterizar la PD (inhibición de la P-selectina) de crizanlizumab en dosis de 5 y 7,5 mg/kg.
Para más objetivos ver protocolo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained prior
to any screening procedures
2. Male or female patients aged 12 years and older
on the day of signing informed consent. Adolescent
include patients aged 12 to 17 years old and adults ≥
18 years and older
3. Confirmed diagnosis of SCD by hemoglobin
electrophoresis or high performance liquid
chromatography (HPLC) [performed locally]. All SCD
genotypes are eligible, genotyping is not required for study entry
4. Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must include:
a. Pain crisis defined as an acute onset of pain for
which there is no other medically determined
explanation other than vaso- occlusion -
b. a visit to a medical facility and/or healthcare
professional,
c. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesia
As well as other complicated crises, such as acute
chest syndrome, priapism, and hepatic or splenic
sequestration
5. If receiving HU/HC or erythropoietin stimulating
agent or L-glutamine, must have been receiving the
drug for at least 6 months prior to Screening visit and plan to continue taking at the same dose and schedule until the subject has reached one year of study treatment
6. Patients must meet the following central
laboratory values at the screening visit:
• Absolute Neutrophil Count ≥1.0 x 109/L
• Platelet count ≥75 x 109/L
• Hemoglobin: for adults (Hb) ≥4.0 g/dL and for
adolescents (Hb) ≥5.5 g/dL
• Glomerular filtration rate ≥ 45 mL/min/1.73 m2
using CKD-EPI formula in adults, and Shwartz formula in adolescents
• Direct (conjugated) bilirubin < 2.0 x ULN
• Alanine transaminase (ALT) < 3.0 x ULN
7. ECOG performance status ≤2.0 for adults and
Karnofsky ≥ 50% for adolescents

1. Se debe obtener un consentimiento informado por escrito antes de realizar cualquier procedimiento de selección.
2. Pacientes de ambos sexos a partir de 12 años de edad el día de la firma del consentimiento informado. Pacientes adolescentes entre 12 y 17 años y adultos >/=18 años.
3. Diagnóstico de ECF confirmado por electroforesis de Hb o cromatografía líquida de alta resolución (HPLC) (realizada de manera local). Todos los genotipos de ECF son elegibles, no es necesario realizar un genotipado para entrar en el estudio.
4. Haber experimentado al menos dos CVO que deriven en visita clínica durante los 12 meses anteriores a la visita de selección, determinado por la historia clínica. Las CVO previas que deriven en visita clínica deben incluir:
a. Crisis de dolor definida como una aparición de dolor agudo cuya única explicación médica puede ser la vaso-oclusión.
b. Una visita a un centro médico o a un profesional sanitario.
c. Y una receta de analgésicos: opioides orales/parenterales o fármacos antinflamatorios no esteroideos (AINE) parenterales.
Así como otras crisis complicadas, como síndrome torácico agudo, priapismo y secuestro esplénico o hepático.
5. Si está recibiendo HU/HC, eritropoyetina recombinante o L-glutamina, debe haber estado recibiendo el fármaco durante al menos 6 meses antes de la visita de selección y tener previsto continuar tomando la misma dosis con la misma pauta hasta que el sujeto haya completado un año del tratamiento del estudio.
6. Los pacientes deben cumplir los siguientes valores del laboratorio central en la visita de selección:
 Recuento absoluto de neutrófilos >/= 1 x 109/l.
 Recuento de plaquetas >/=75 x 109/l.
 Hemoglobina: para adultos (Hb) >/=4 g/dl y para adolescentes (Hb) >/=5,5 g/dl.
 Tasa de filtración glomerular >/=45 ml/min/1,73 m2 mediante la fórmula CKD-EPI en adultos y la fórmula Schwartz en adolescentes.
 Bilirrubina directa (conjugada) <2 x LSN.
 Alanina aminotransferasa (ALT) <3 × LSN.
7. Estado funcional ECOG </=2 para adultos y Karnofsky >/=50 % para adolescentes.

E.4

Principal exclusion criteria

1. History of stem cell transplant.
2. Participating in a chronic transfusion program
(pre-planned series of transfusions for prophylactic
purposes) and/or planning on undergoing an
exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.
3. Contraindication or hypersensitivity to any drug or
metabolites from similar class as study drug or to any excipients of the study drug formulation. History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
4. Received active treatment on another
investigational trial within 30 days (or 5 half-lives of
that agent, whichever is greater) prior to Screening
visit or plans to participate in another investigational
drug trial.
5. Women of child-bearing potential, defined as all
women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment.
6. Concurrent severe and/or uncontrolled medical
conditions which, in the opinion of the Investigator,
could cause unacceptable safety risks or compromise participation in the study.
7. History or current diagnosis of ECG abnormalities
indicating significant risk of safety such as:
• Resting QTcF ≥470 msec at pretreatment
(baseline) for both male and female or inestability to
determine QTc
• Concomitant clinically significant cardiac
arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker
• History of familial long QT syndrome or know
family history of Torsades de Pointes
8. Not able to understand and to comply with study
intructions and requirements.

1. Antecedente de trasplante de células madre.
2. La participación en un programa de transfusión crónica (series de transfusiones previstas con fines profilácticos) o previsión de una exanguinotransfusión durante el estudio; se permite la transfusión episódica en caso de anemia empeorada o CVO.
3. Contraindicación o hipersensibilidad a algún fármaco o metabolitos de clase similar al fármaco del estudio o a cualquier excipiente de la formulación del fármaco del estudio. Antecedentes de reacción grave de hipersensibilidad a otros anticuerpos monoclonales, que según la opinión del investigador pueda suponer un mayor riesgo de reacción grave a la perfusión.
4. Haber recibido tratamiento activo en otro ensayo de investigación durante los 30 días (o 5 semividas de ese fármaco, aquel periodo que sea mayor) anteriores a la visita de selección o tener previsto participar en otro ensayo con fármacos en investigación.
5. Mujeres en edad fértil, definidas como toda mujer fisiológicamente capaz de quedarse embarazada, salvo que esté utilizando métodos anticonceptivos altamente eficaces durante la administración de la dosis y durante las 15 semanas posteriores a la finalización del tratamiento.
6. Enfermedades concurrentes, incontroladas o graves que, según el criterio del investigador, podrían causar riesgos de seguridad inaceptables o comprometer la participación en el estudio.
7. Antecedentes o diagnóstico actual de anomalías en el ECG que indiquen un riesgo significativo en la seguridad como:
 -QTcF en reposo >/=470 ms en el pretratamiento (basal) para ambos sexos o inestabilidad para determinar el QTc.
 -Arritmias cardíacas concomitantes clínicamente significativas (p. ej., taquicardia ventricular) y bloqueo AV de segundo o tercer grado sin marcapasos clínicamente significativo.
 -Antecedentes familiares de síndrome de QT largo o antecedentes familiares de Torsades de Pointes.
8. Incapaz de comprender y cumplir las instrucciones y requisitos del estudio

E.5 End points

E.5.1

Primary end point(s)

Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post-randomization

Tasa anual de CVO que deriven en visita clínica durante el primer año después de la aleatorización

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year

1 año

E.5.2

Secondary end point(s)

for key secondary:
- Annualized rate of all VOCs leading to healthcare
visit and treated at home (based on documentation by health care provider following contact with subject) over the first year post randomization

- The time to first and second VOC calculated
respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year post randomization
- Number of days with VOC leading to healthcare
visit over the first year post randomization
- Number and percentage of subjects free from
VOCs leading to healthcare visit in each group
over the first year post randomization
- Annualized rate of visits to clinic, Emergency room
(ER) and hospitalizations, both overall and VOCrelated over the first year post randomization
- Evolution of albuminuria and ACR over the first
year post randomization
- PK parameters after the first and fifth dose (e.g.,
AUC, Cmax, Tmax, half-life)
- PD parameter (P-selectin inhibition) after the first
and fifth dose
- Annualized rate of VOCs leading to healthcare
visit
Annualized rate of VOCs managed at home
Number, seriousness, severity, and causality
assessments of treatment-emergent adverse
events, including infections (serious, non-serious
and opportunistic infections) and other safety data
as considered appropriate
Absolute change from baseline in hemoglobin
Growth and sexual maturity assessment in
adolescents (Tanner stage)
Immunogenicity: measurement of anti-drug
antibodies (ADA) to crizanlizumab

Para la variable secundaria principal:
-Tasa anual de todas las CVO que deriven en visita clínica y las tratadas en el domicilio (según la documentación del profesional sanitario que sigue el contacto con el sujeto) durante el primer año después de la aleatorización.
-Tiempo hasta la primera y segunda CVO calculado respectivamente como el tiempo desde la fecha de aleatorización hasta la primera y segunda CVO que deriven en visita clínica durante el primer año después de la aleatorización.
-Número de días con CVO que deriven en visita clínica durante el primer año después de la aleatorización.
-Número y porcentaje de sujetos sin CVO que deriven en visita clínica en cada grupo durante el primer año después de la aleatorización.
-Tasa anual de las visitas al centro, urgencias (URG.) y hospitalizaciones, generales y relacionadas con CVO durante el primer año después de la aleatorización.
-Evolución de albuminuria y CAC durante el primer año después de la aleatorización.
-Parámetros PK después de la dosis inicial y de la quinta dosis (p. ej., AUC, Cmax, Tmax y semivida).
-Parámetro PD (inhibición de la P-selectina) después de la dosis inicial y de la quinta dosis.
-Tasa anual de CVO que deriven en visita clínica.
Tasa anual de CVO tratadas en el domicilio.
Evaluaciones de número, gravedad, intensidad y causalidad de los acontecimientos adversos que aparecieron con el tratamiento, incluyendo infecciones (graves, no graves y oportunistas) y otros datos de seguridad si se considera apropiado.
Cambio absoluto respecto a la basal en la hemoglobina.
Evaluación de crecimiento y madurez sexual (estadio de Tanner).
Inmunogenicidad: medición de anticuerpos contra el fármaco (ADA) crizanlizumab.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year

- 1 year
- 5 years
- 5 years
- 5 years
- 5 years
- 5 years
- 5 years
- 5 years

1 año

-1 año
-5 años
-5 años
-5 años
-5 años
-5 años
-5 años
-5 años

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

Yes

E.6.13.1

Other scope of the trial description

healthcare resource utilization

Uso de recursos sanitarios

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Brazil

Canada

Colombia

Egypt

Finland

France

Germany

Ghana

Greece

India

Italy

Kenya

Lebanon

Netherlands

Oman

Panama

Saudi Arabia

South Africa

Spain

Turkey

United Arab Emirates

United Kingdom

United States

Jordan

E.8.7

Trial has a data monitoring committee

Yes

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

Último paciente última visita

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

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:

190

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

240

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)

Novartis will provide crizanlizumab to subjects who benefit from continued treatment as
per the Investigator's opinion after study completion until the earliest occurrence :
- Crizanlizumab is commercially available and reimbursed in the subject's country for this population, and subjects are eligible to be prescribed the commercial drug
- Another clinical study becomes available that can continue to provide crizanlizumab in
this population 
- Subject is no longer deriving benefit

Novartis proporcionará crizanlizumab a sujetos que se benefician de un tto continuado según el investigador una vez finalizado el estudio y hasta el caso que ocurra primero de los siguientes: -Crizanlizumab está comercializado y se reembolsa en el país del sujeto para esta población y los sujetos son elegibles para que se les prescriba el fármaco comercial. -Se dispone de otro estudio clínico que puede continuar proporcionando crizanlizumab a esta población. -El sujeto ya no obtiene beneficio.

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

2019-10-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-13

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

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IMP with orphan designation in the indication
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