Clinical Trials Register

Summary
EudraCT Number:	2020-003413-35
Sponsor's Protocol Code Number:	WN42349
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-003413-35

A.3

Full title of the trial

A MULTICENTER, SINGLE ARM, OPEN-LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY AND EFFICACY OF SATRALIZUMAB IN PATIENTS WITH NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD)

STUDIO MULTICENTRICO, A SINGOLO BRACCIO, IN APERTO PER VALUTARE LA SICUREZZA E L’EFFICACIA A LUNGO TERMINE DI SATRALIZUMAB IN PAZIENTI CON DISTURBO DELLO SPETTRO DELLA NEUROMIELITE OTTICA (NMOSD)

A.3.1

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

A MULTICENTER, SINGLE ARM, OPEN-LABEL STUDY TO EVALUATE THE LONG-TERM SAFETY AND EFFICACY OF SATRALIZUMAB IN PATIENTS WITH NEUROMYELITIS OPTICA SPECTRUM DISORDER (NMOSD)

STUDIO MULTICENTRICO, A SINGOLO BRACCIO, IN APERTO PER VALUTARE LA SICUREZZA E L’EFFICACIA A LUNGO TERMINE DI SATRALIZUMAB IN PAZIENTI CON DISTURBO DELLO SPETTRO DELLA NEUROMIELITE OTTICA (NMOSD)

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

WN42349

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	F. HOFFMANN - LA ROCHE LTD.
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
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	F. Hoffman-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	000000
B.5.5	Fax number	000000
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Yes
D.2.1.1.1	Trade name	Enspryng
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.3.1	Product name	Satralizumab
D.3.2	Product code	[RO5333787]
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SATRALIZUMAB
D.3.9.1	CAS number	1535963-91-7
D.3.9.2	Current sponsor code	RO5333787
D.3.9.4	EV Substance Code	SUB195082
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	120
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Neuromyelitis Optic Spectrum Disorder

Disturbo dello spettro della neuromielite ottica

E.1.1.1

Medical condition in easily understood language

Neuromyelitis Optic Spectrum Disorder

Disturbo dello spettro della neuromielite ottica

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10077875
E.1.2	Term	Neuromyelitis optica spectrum disorder
E.1.2	System Organ Class	10029205 - Nervous system disorders

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

Safety Objective
- To evaluate the long-term safety of satralizumab in patients with NMOSD.
Efficacy Objective
The efficacy objective for this study is to evaluate long-term efficacy of satralizumab on the basis of the following endpoints:
- Time to first relapse (TFR) and proportion of patients who are relapsefree
- Annualized relapse rate (ARR)
- Change in Expanded Disability Status Scale (EDSS) score
- Time to EDSS worsening and proportion of patients without EDSS worsening
-Change in visual acuity

Obiettivo di sicurezza
- Valutare la sicurezza a lungo termine di satralizumab in pazienti con NMOSD.
Obiettivo di efficacia
L’obiettivo di efficacia di questo studio è valutare l’efficacia a lungo termine di satralizumab sulla base dei seguenti endpoint:
- Tempo alla prima ricaduta (TFR) e percentuale di pazienti senza ricadute
- Tasso annualizzato di ricadute (ARR)
- Modifica del punteggio EDSS (Expanded Disability Status Scale)
- Tempo al peggioramento dell’EDSS e percentuale di pazienti senza peggioramento dell’EDSS
- Alterazione dell’acuità visiva

E.2.2

Secondary objectives of the trial

To further evaluate the risks of serious infections and hepatotoxicity in patients with NMOSD who are treated with satralizumab

Valutare ulteriormente i rischi di infezioni gravi ed epatotossicità in pazienti con NMOSD trattati con satralizumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet the following criteria for study entry:
- Participated in Study BN40898 or Study BN40900 with satralizumab in NMOSD, are on ongoing satralizumab treatment and were AQP4-IgG seropositive at screening in these studies. Patients with NMOSD who were AQP4-IgG seronegative at screening in Study BN40898 or Study BN40900 can be enrolled if the investigator considers the continued treatment with satralizumab to be beneficial for the patient.
- Signed Informed Consent Form (ICF).
- Ability to comply with the study protocol
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 3 months after the final dose of satralizumab.
A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (=12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
The following are examples of adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormonereleasing intrauterine devices; copper intrauterine devices; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local ICF.

I pazienti devono soddisfare i seguenti criteri per l’ammissione allo studio:
- Partecipazione allo studio BN40898 o allo studio BN40900 con satralizumab sul NMOSD, trattamento in corso con satralizumab e sieropositività ad AQP4-IgG allo screening in questi studi. I pazienti con NMOSD risultati sieronegativi ad AQP4-IgG allo screening nello studio BN40898 o nello studio BN40900 possono essere arruolati qualora lo sperimentatore ritenga la prosecuzione del trattamento con satralizumab di beneficio per il paziente.
- Modulo di consenso informato (ICF) firmato.
- Capacità di rispettare il protocollo di studio
- Per le donne in età fertile: consenso all’astinenza (astenersi da rapporti eterosessuali) o all’utilizzo di misure contraccettive adeguate durante il periodo di trattamento e per 3 mesi dopo la dose finale di satralizumab.
Una donna si considera in età fertile quando si trova in età postmenarca e prima di raggiungere uno stato postmenopausale (=12 mesi continui di amenorrea senza causa identificata diversa dalla menopausa), a esclusione di una condizione di sterilità permanente a seguito di un intervento chirurgico (ovvero, rimozione di ovaie, tube di Falloppio e/o utero) o in ragione di un’altra causa secondo quanto determinato dallo sperimentatore (per es., agenesia mülleriana). La definizione
di “in età fertile” può essere adattata in modo da allinearsi con le linee guida o le normative locali.
Di seguito sono riportati alcuni esempi di metodi contraccettivi adeguati: legatura delle tube bilaterale; sterilizzazione maschile; contraccettivi ormonali; dispositivi intrauterini a rilascio di ormoni; dispositivi intrauterini in rame; profilattico maschile o femminile con o senza spermicida; cappuccio, diaframma o spugna con spermicida. L’affidabilità dell’astinenza sessuale dovrebbe essere valutata in rapporto alla durata della sperimentazione clinica e allo stile di vita preferito e abituale della paziente. Astinenza periodica (per es., metodo Ogino-Knaus, metodo dell’ovulazione Billings, metodo sintotermico o metodo post-ovulatorio) e coito interrotto non sono metodi adeguati di contraccezione. Se richiesto dalle linee guida o dalle normative locali, l’ICF locale includerà una descrizione dei metodi contraccettivi localmente riconosciuti come adeguati e informazioni in merito all’affidabilità dell’astinenza.

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from study entry:
- Use of prohibited medication
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of study drug. Women of childbearing potential must have a negative urine pregnancy test result on the baseline visit prior to initiation of study drug.
- Evidence of any serious uncontrolled concomitant diseases that may preclude patient participation, such as: other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency.
- Known active infection that requires delaying the next satralizumab dose at the time of enrollment a a In case of an active infection, the patient should remain in the parent study, as governed by that protocol, and may enroll in this study once the active infection is controlled.
- NMOSD relapse at the time of enrollment .In case of a relapse, the patient should remain in the parent study, as governed by that protocol, and may enroll in this study once the patient is stable.
- Laboratory abnormalities at the last assessment in Study BN40898 or Study BN40900 that preclude re-treatment with satralizumab . If a patient does not meet the criteria to restart treatment with satralizumab based on laboratory assessments, the patient should remain in the parent study and the baseline visit should be delayed. The last assessment before enrollment must meet the re-treatment criteria.

I pazienti che soddisfano uno qualsiasi dei seguenti criteri verranno esclusi dalla partecipazione allo studio:
- Uso di farmaci non consentiti
- Gravidanza o allattamento, o intenzione di rimanere incinta durante lo studio o entro 3 mesi dall’ultima dose del farmaco in studio. Le donne in età fertile devono sottoporsi a un test di gravidanza sulle urine che deve risultare negativo alla visita basale prima dell’inizio del trattamento con il farmaco in studio.
- Evidenza di qualsiasi malattia concomitante grave non controllata che possa precludere la partecipazione del paziente, come ad esempio: altre malattie del sistema nervoso, malattie cardiovascolari, malattie ematologiche/emopoiesi, malattie respiratorie, malattie muscolari, malattie endocrine, malattie renali/urologiche, malattie del sistema digerente, immunodeficienza grave congenita o acquisita.
- Infezione attiva nota che richiede la posticipazione della successiva dose di satralizumab al momento dell’arruolamento. In caso di infezione attiva, il paziente deve rimanere nello studio originario, come disciplinato dal relativo protocollo, con la possibilità di arruolarsi in questo studio una volta che l’infezione attiva sarà stata controllata.
- Ricaduta del NMOSD al momento dell’arruolamento. In caso di ricaduta, il paziente deve rimanere nello studio originario, come disciplinato dal relativo protocollo, con la possibilità di arruolarsi in questo studio una volta che il paziente risulterà stabile.
- Anomalie di laboratorio all’ultima valutazione nell’ambito dello studio BN40898 o dello studio BN40900 che precludono la ripresa del trattamento con satralizumab . Se un paziente non soddisfa i criteri per la ripresa del trattamento con
satralizumab sulla base di valutazioni di laboratorio, dovrà rimanere nello studio originario e la visita basale dovrà essere posticipata. L’ultima valutazione prima dell’arruolamento deve soddisfare i criteri di ripresa del trattamento.

E.5 End points

E.5.1

Primary end point(s)

- Incidence and severity of adverse events (AE), adverse events of special interest (AESI), serious AEs (SAE), and selected AEs
- Vital signs (temperature, blood pressure, and pulse rate), clinical laboratory tests (hematology, chemistry, and urinalysis), 12-lead
electrocardiograms (ECG), and suicidality (Columbia-Suicide Severity Rating Scale [C-SSRS])

- Incidenza e gravità di eventi avversi (EA), eventi avversi di interesse speciale (AESI), eventi avversi gravi (SAE) ed eventi avversi selezionati
- Segni vitali (temperatura, pressione sanguigna e frequenza cardiaca), test clinici di laboratorio (ematologia, ematochimica e analisi delle urine), elettrocardiogramma a 12 derivazioni (ECG) e propensione al suicidio (Columbia-Suicide Severity Rating Scale [C-SSRS])

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

All efficacy analyses will be based on the ITT population and the ALLSA population. For both populations, data from Study WN42349 will be combined with data from the Studies BN40898 and BN40900. The definitions are in line with Studies BN408989 and BN40900 to investigate long-term efficacy by summarizing the data of the parental studies and this Study WN42349.

Tutte le analisi di efficacia saranno basate sulla popolazione ITT e sulla popolazione ALLSA. Per entrambe le popolazioni, i dati dello studio WN42349 saranno combinati con i dati degli studi BN40898 e BN40900. Le definizioni sono in linea con gli studi BN408989 e BN40900 al fine di indagare l’efficacia a lungo termine mediante riepilogo dei dati degli studi originali e del presente studio WN42349.

E.5.2.1

Timepoint(s) of evaluation of this end point

The time to first relapse (TFR) efficacy endpoint is based on several endpoint definitions to accommodate different estimand strategies. The most important intercurrent event is the use of therapy for the treatment of an acute NMOSD relapse (rescue therapy). For the treatment policy strategy, the use of rescue therapy is ignored. Therefore, in the analysis for the treatment policy estimand the TFR is defined as the time from randomization in ITT or first dose of satralizumab in ALLSA to the first protocol-defined relapse as assessed by the investigator (iPDR).

L’endpoint di efficacia del tempo alla prima ricaduta (TFR) si basa su diverse definizioni dell’endpoint per coerenza con diverse strategie di estimand. Il più importante evento intercorrente è l’uso della terapia per il trattamento di una ricaduta di NMOSD acuta (terapia di salvataggio). Per la strategia basata sulla politica di trattamento, l’uso della terapia di salvataggio viene ignorato. Pertanto, nell’analisi per l’estimand della politica di trattamento e il TFR è definito come il tempo dalla randomizzazione in ITT o dalla prima dose di satralizumab in ALLSA alla prima ricaduta definita dal protocollo secondo quanto valutato dallo sperimentatore (iPDR).

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

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

in aperto

open label

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.8.2.4

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

Information not present in EudraCT

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

Canada

Georgia

Japan

Korea, Republic of

Malaysia

Taiwan

Turkey

Ukraine

United States

Bulgaria

Croatia

Hungary

Italy

Poland

Romania

Spain

United Kingdom

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

The end of this study is defined as the date when the last patient, last visit (LPLV), occurs. The treatment period ends 3 years after the date
the first patient enrolls in the study.

Il termine di questo studio è definito come la data dell’ultima visita dell’ultimo paziente (LPLV). Il periodo di trattamento termina 3 anni dopo la data di arruolamento del primo paziente nello studio.

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.1.1.1

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:

116

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

127

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)

The Sponsor will offer continued access to Roche IMP satralizumab free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.
The Roche Global Policy on Continued Access to Investigational Medicinal Product is available at the following Website:
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

Lo sponsor offrirà un accesso continuato e gratuito al medicinale sperimentale satralizumab di Roche per i pazienti idonei in conformità alla Politica globale di Roche sull’accesso continuato al medicinale sperimentale.
La Politica globale di Roche sull’accesso continuato al farmaco sperimentale è disponibile sul seguente sito Web:
http://www.roche.com/policy_continued_access_to_investigational_medicine.pdf

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

2021-01-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-10

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

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