Clinical Trials Register

Summary
EudraCT Number:	2022-001092-14
Sponsor's Protocol Code Number:	TIGEM5_USH
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:	2022-06-30
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

2022-001092-14

A.3

Full title of the trial

A phase I/II open label, dose escalation study of sub-retinal administration of a “mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A gene and the 3 ´- half sequence of the human MYO7A gene” in subjects with Usher syndrome type 1B (USH1B) retinitis pigmentosa.

Studio di fase I/II in aperto, con incremento di dose, sulla somministrazione sottoretinica di una miscela di due vettori virali adeno-associati di sierotipo 8 contenenti la metà al 5 ´ del gene umano MYO7A e la metà al 3 ´ del gene umano MYO7A rispettivamente, in soggetti con retinite pigmentosa da sindrome di Usher di tipo 1B (USH1B).

A.3.1

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

A phase I/II open label clinical trial, dose escalation study, involving a single injection under the retina of one eye of a mixture of two genetically modified viruses each containing one of the two halves of the human gene MYO7A, in subjects with Usher Syndrome type 1B retinitis pigmentosa.

Sperimentazione clinica di fase I/II in aperto, con aumento della dose di farmaco, che prevede una singola somministrazione sotto la retina di un solo occhio di un farmaco sperimentale composto da una miscela di due virus modificati geneticamente ciascuno contenente una delle due metà del gene umano MYO7A, in soggetti con retinite pigmentosa da Sindrome di Usher di tipo 1B.

A.3.2

Name or abbreviated title of the trial where available

TIGEM5_USH

A.4.1

Sponsor's protocol code number

TIGEM5_USH

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	FONDAZIONE TELETHON
B.1.3.4	Country	Italy
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	COMUNITÀ EUROPEA - GRANT AGREEMENT NUMBER — 754848 — UshTher
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FONDAZIONE TELETHON ETS
B.5.2	Functional name of contact point	SVILUPPO CLINICO
B.5.3	Address:
B.5.3.1	Street Address	VIA VARESE 16/B
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00185
B.5.3.4	Country	Italy
B.5.6	E-mail	szancan@telethon.it

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.2.1.2	Country which granted the Marketing Authorisation	Italy
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	PREDNISONE
D.3.2	Product code	[PREDNISONE]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PREDNISONE
D.3.9.2	Current sponsor code	PREDNISONE
D.3.9.4	EV Substance Code	H02AB
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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.IMP: 2
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/3/14/1282
D.3 Description of the IMP
D.3.1	Product name	Dual AAV8.MYO7A
D.3.2	Product code	[Dual AAV8.MYO7A]
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	Dual AAV8.MYO7A
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	457000000
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	MEDICINALE ORFANO EU/3/14/1282
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	Yes
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

Usher syndrome (USH) is characterized by the association of sensorineural hearing loss, Retinitis Pigmentosa (RP), and, in some cases, vestibular dysfunction. It is the most frequent cause of deaf-blindness. Retinal features in USH patients consist into a progressive photoreceptor degeneration, which leads to a loss of peripheral vision. This degeneration is predominantly attributable to rod dysfunction, although cones usually degenerate later in the course of the disease.

La sindrome di Usher (USH) è caratterizzata dall'associazione di ipoacusia neurosensoriale, retinite pigmentosa (RP) e, in alcuni casi, disfunzione vestibolare. È la causa più frequente di sordocecità. Le caratteristiche retiniche nei pazienti con USH consistono in una progressiva degenerazione dei fotorecettori, con perdita della visione periferica, principalmente attribuibile alla disfunzione del bastoncello, sebbene i coni di solito degenerino più tardi nel corso della malattia.

E.1.1.1

Medical condition in easily understood language

Usher syndrome type 1B is characterized by sensorineural hearing loss associated with retinitis pigmentosa, which causes progressive vision loss, and in some cases a balance disorder.

La sindrome di Usher di tipo 1B è caratterizzata da sordità neurosensoriale associata a retinite pigmentosa, che causa la perdita progressiva della vista, e in alcuni casi a disturbi dell'equilibrio.

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10063396
E.1.2	Term	Usher's syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10063396
E.1.2	Term	Usher's syndrome
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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

Primary (Safety): 1) To assess the safety and tolerability of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A coding sequence to deliver the full-lenght coding sequence for human MYO7A in subjects with USH1B retinitis pigmentosa
2) To determine the Maximum Tolerated Dose (MTD).

Obiettivi primari (Sicurezza):
1) Valutare la sicurezza e la tollerabilità della somministrazione sottoretinica della miscela di due vettori virali adeno-associati del sierotipo 8 contenenti metà della sequenza al 5 ´ del gene umano MYO7A e metà della sequenza al 3 ´ del gene umano MYO7A rispettivamente, in soggetti con retinite pigmentosa da USH1B.
2) Determinare la dose massima tollerata (MTD).

E.2.2

Secondary objectives of the trial

Secondary (Efficacy): To investigate the objective clinical ophthalmological measures of efficacy of subretinal administration of the mixture of two adeno-associated viral vectors of serotype 8 containing the 5 ´- half sequence of the human MYO7A coding sequence and the 3 ´- half sequence of the human MYO7A gene to deliver the full-lenght coding sequence for human MYO7A to subjects with USH1B retinitis pigmentosa.

Obiettivo secondario (Efficacia):
1) Studiare le misure cliniche oggettive oftalmologiche di efficacia della somministrazione sottoretinica della miscela di due vettori virali adeno-associati di sierotipo 8 contenenti metà della sequenza al 5 ´ del gene umano MYO7A e metà della sequenza al 3 ´ del gene umano MYO7A rispettivamente, in soggetti con retinite pigmentosa da USH1B.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part A:
1. Willingness to adhere to the protocol as evidenced by written informed consent.
2. Male and female adults diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eighteen years old or older at the time of
administration.
5. 20/400 = Visual acuity = 20/80 and/or 5° < visual field <
20° in the eye to be injected.
6. Female subjects of childbearing potential have to use a
double method of contraception for 1 year after treatment. Male subjects who are partner of childbearing potential individual must use condom for 1 year after treatment.
Part B Cohort 1:
1. Willingness to adhere to the protocol as evidenced by written informed consent.
2. Male and female adults diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eighteen years old or older at the time of
administration.
5. 20/200 = Visual acuity = 20/40 and/or 20° < visual field <
40° in the eye to be injected.
6. Female subjects of childbearing potential have to use a double method of contraception for the duration of 1 year. after treatment. Male subjects who are partner of childbearing potential individual must use a condom during intercourse for 1 year after treatment.
Part B Cohort 2:
1. Willingness to adhere to protocol as evidenced by written informed consent or parental informed consent and subject assent.
2. Male and female adults and children diagnosed with USH1.
3. Molecular diagnosis of USH1B due to MYO7A mutations
(homozygotes or compound heterozygotes).
4. Age eight years old or older at the time of administration.
5. 20/200 = Visual acuity = 20/40 and/or 20° < visual field <
40° in the eye to be injected.
6. Female subjects of childbearing potential have to use a double method of contraception for the duration of 1 year. after treatment. Male subjects who are partner of childbearing potential individual must use a condom during intercourse for 1 year after treatment.

Parte A:
1) Disponibilità ad aderire al protocollo come evidenziato dalla firma del consenso informato.
2) Adulti di sesso maschile e femminile con diagnosi di USH1.
3) Diagnosi molecolare di USH1B con mutazioni nel gene MYO7A (omozigoti o eterozigoti composti).
4) Età maggiore di diciotto anni al momento della somministrazione.
5) 20/400 = Acuità visiva = 20/80 e/o 5° < campo visivo < 20° nell'occhio da iniettare.
6) I soggetti di sesso femminile in età fertile devono utilizzare un doppio metodo contraccettivo per 1 anno dopo il trattamento. I soggetti di sesso maschile che sono partner di una persona potenzialmente fertile devono usare il preservativo per 1 anno dopo il trattamento.

Parte B Coorte 1:
1) Disponibilità ad aderire al protocollo come evidenziato dalla firma del consenso informato.
2) Adulti di sesso maschile e femminile con diagnosi di USH1.
3) Diagnosi molecolare di USH1B con mutazioni nel gene MYO7A (omozigoti o eterozigoti composti).
4) Età maggiore di diciotto anni al momento della somministrazione.
5) 20/200 = Acuità visiva = 20/40 e/o 20° < campo visivo < 40° nell'occhio da iniettare.
6) I soggetti di sesso femminile in età fertile devono utilizzare un doppio metodo contraccettivo per la durata di 1 anno. dopo il trattamento. I soggetti di sesso maschile che sono partner di un potenziale individuo fertile devono usare un preservativo durante il rapporto sessuale per 1 anno dopo il trattamento.

Parte B Coorte 2:
1) Disponibilità ad aderire al protocollo come evidenziato dalla firma del consenso informato o del consenso informato dei genitori e dell’assenso del soggetto minore.
2) Adulti e bambini di sesso maschile e femminile con diagnosi di USH1.
3) Diagnosi molecolare di USH1B con mutazioni nel gene MYO7A (omozigoti o eterozigoti composti).
4) Età di otto anni o più al momento della somministrazione.
5) 20/200 = Acuità visiva = 20/40 e/o 20° < campo visivo < 40° nell'occhio da iniettare.
6) I soggetti di sesso femminile in età fertile devono utilizzare un doppio metodo contraccettivo per 1 anno dopo il trattamento. I soggetti di sesso maschile che sono partner di un potenziale individuo fertile devono usare un preservativo durante il rapporto sessuale per 1 anno dopo il trattamento.

E.4

Principal exclusion criteria

1. Unable or unwilling to meet requirements of the study.
2. Unable to communicate with suitable verbal/auditory and/or
tactile sign language (in the opinion of the investigator).
3. Participation in a clinical study with an investigational drug in
the past six months.
4. Pre-existing eye conditions that would preclude the planned
surgery or interfere with the interpretation of study endpoints (for example, glaucoma, corneal or significant lenticular opacities, cystoid macular oedema, macular hole, uveitis).
5. Lack of sufficient viable retinal cells as determined by non- invasive means, such as OCT. Specifically, if indirect ophthalmoscopy reveals less than 1 disc area of retina which is not involved by complete retinal degeneration (indicated by geographic atrophy, thinning with tapetal sheen, or confluent intraretinal pigment migration), these eyes will be excluded. In addition, in eyes where OCT scans of sufficient quality can be obtained, areas of retina with thickness measurements less than 100 µm, or absence of neural retina, will not be targeted for delivery of dual AAV8 vector.
6. Complicating systemic diseases or clinically significant abnormal baseline laboratory values. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example, radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Also excluded would be subjects with immuno- compromising diseases, as there could be susceptibility to opportunistic infection (such as CMV retinitis). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Subjects with juvenile rheumatoid arthritis could be excluded due to increased infection risk after surgery due to poor wound healing. Subjects who are positive for hepatitis B, C, and HIV will be excluded.
7. Prior ocular surgery within six months.
8. Known sensitivity to medications planned for use in the peri-
operative period.
9. Individuals who are pregnant or nursing
10. Any other condition that would not allow the potential subject
to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.

1) Impossibilità o non volontà di soddisfare i requisiti dello studio;
2) Impossibilità di comunicare con un linguaggio dei segni verbale/uditivo e/o tattile adeguato (a giudizio dello Sperimentatore);
3) Partecipazione ad uno studio clinico con un farmaco sperimentale negli ultimi sei mesi;
4) Condizioni oculari preesistenti che precluderebbero l'intervento chirurgico pianificato o interferirebbero con l'interpretazione degli endpoint dello studio (ad esempio, glaucoma, opacità corneali o lenticolari significative, edema maculare cistoide, foro maculare, uveite);
5) Mancanza di cellule retiniche vitali sufficienti, determinata con mezzi non invasivi, come l'OCT. In particolare, se l'oftalmoscopia indiretta rivela meno di 1 area del disco della retina che non è coinvolta dalla degenerazione retinica completa (indicata da atrofia geografica, assottigliamento con riflesso tapetale o iperpigmentazione dell'epitelio pigmentato retinico), questi occhi saranno esclusi. Inoltre, negli occhi in cui è possibile ottenere scansioni OCT di qualità sufficiente, le aree della retina con misurazioni dello spessore inferiori a 100 µm, o con assenza di retina neurale, non saranno utilizzati come bersaglio per la consegna del vettore duale AAV8;
6) Malattie sistemiche con complicanze o valori di laboratorio al basale anormali clinicamente significativi. Le malattie sistemiche con complicanze includerebbero quelle in cui la malattia stessa, o il trattamento per la malattia, può alterare la funzione oculare. Esempi sono le neoplasie il cui trattamento potrebbe influenzare la funzione del sistema nervoso centrale (ad esempio, radioterapia dell'orbita; leucemia con coinvolgimento del sistema nervoso centrale/nervo ottico). Saranno esclusi anche i soggetti con malattie immuno-compromettenti, in quanto potrebbero esserci suscettibilità alle infezioni opportunistiche (come la retinite da CMV). I soggetti con diabete o anemia falciforme sarebbero esclusi se presentassero manifestazioni di retinopatia avanzata (es. edema maculare o alterazioni proliferative). I soggetti con artrite reumatoide giovanile potrebbero essere esclusi a causa dell'aumento del rischio di infezione dopo l'intervento chirurgico a causa della scarsa guarigione delle ferite. Saranno esclusi i soggetti positivi all'epatite B, C e HIV;
7) Precedente intervento chirurgico oculare entro sei mesi;
8) Nota sensibilità ai farmaci previsti per l'uso nel periodo peri-operatorio;
9) Donne in gravidanza o allattamento;
10) Qualsiasi altra condizione che non consenta al potenziale soggetto di completare gli esami di follow-up nel corso dello studio e, a giudizio dello Sperimentatore, renda il potenziale soggetto inadatto allo studio.

E.5 End points

E.5.1

Primary end point(s)

1) The incidence and severity of adverse events (AEs) including serious adverse events (SAEs).
2) The number and proportion of dose-limiting toxicities (DLTs) at each dose level.

1) L'incidenza e la gravità degli eventi avversi (AE) inclusi gli eventi avversi seri (SAE).
2) Il numero e la proporzione delle tossicità dose-limitanti (DLT) a ciascun livello di dose.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary safety endpoints will be monitored in the days immediately following the administration of the drug and during the following the weeks, months and years, ie at visits: Visit 1 - Day 0 (day of injection); Visit 2 - Day 2; Visit 3 - Day 3; Visit 4 - Day 7; Visit 5 - Day 14; Visit 6 - Day 45; Visit 7 - Day 90; Visit 8 - Day 180; Visit 9 - Day 270; Visit 10 - 1 year after the injection; and in subsequent visits up to 3 years after the injection, as per the clinical protocol study design.

Gli endpoints primari di sicurezza saranno monitorati nei giorni immediatamente successivi alla somministrazione dell'IMP e nelle settimane, mesi e anni successivi, ovvero alle seguenti visite: Visita 1 - Giorno 0 (giorno dell'iniezione); Visita 2 - Giorno 2; Visita 3 - Giorno 3; Visita 4 - Giorno 7; Visita 5 - Giorno 14; Visita 6 - Giorno 45; Visita 7 - Giorno 90; Visita 8 - Giorno 180; Visita 9 - Giorno 270; Visita 10 - 1 anno dopo l'iniezione e nelle successive visite fino a 3 anni dopo l'iniezione, come previsto dal disegno dello studio del protocollo clinico.

E.5.2

Secondary end point(s)

To assess the evolution in the retinal degeneration following subretinal injection of the Investigational Medicinal Product (IMP) in Part B of the study, the following clinical investigations will be conducted and evaluation at 6 months post IMP administration will be compared to baseline values as described below:
• The main efficacy endpoint is an improvement in light sensitivity threshold measured with the full-field sensitivity threshold test.
Other efficacy endpoints include:
• Improvement in maximum constriction, as assessed by chromatic pupillometry test;
• Enlargement of visual field, as assessed by semiautomic kinetic visual field;
• Improvement of macular sensitivity, as assessed by microperimetry;
• Finally, for patients older than 16 years, change in quality of life assessments will be evaluated.

Per valutare l'evoluzione della degenerazione retinica dopo l'iniezione sottoretinica del farmaco sperimentale nella Parte B dello studio, saranno condotte le seguenti indagini cliniche e la valutazione a 6 mesi dopo la somministrazione dell'IMP sarà confrontata con i valori basali come descritto di seguito:
• Il principale endpoint di efficacia consiste in un miglioramento della soglia di sensibilità alla luce misurata con il test della soglia di sensibilità alla luce.
Altri endpoint di efficacia includono:
• Miglioramento della massima costrizione, misurata attraverso il test di pupillometria cromatica;
• Allargamento del campo visivo, valutato attraverso l’esame del campo visivo cinetico semiautomatico;
• Miglioramento della sensibilità maculare, valutata mediante microperimetria;
• Infine, per i pazienti di età superiore ai 16 anni, sarà valutato il cambiamento nella valutazione della qualità della vita.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary efficacy endpoints will be assessed prior to the administration of the IMP (at baseline) and post IMP injection at the following visits: Visit 6 - Day 45; Visit 8 - Day 180; Visit 10 - 1 year after the injection; Visit 12 - 2 years after the injection; Visit 14 - 3 years after injection, as per the clinical protocol study design.

Gli endpoint secondari di efficacia saranno valutati prima della somministrazione dell'IMP (al basale) e successivamente alle seguenti visite: Visita 6 - Giorno 45; Visita 8 - Giorno 180; Visita 10 - 1 anno dopo l'iniezione; Visita 12 - 2 anni dopo l'iniezione; Visita 14 - 3 anni dopo l'iniezione, come previsto dal disegno dello studio del protocollo clinico.

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

E.6.7

Pharmacodynamic

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)

Yes

E.7.1.1

First administration to humans

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

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:

F.1.3

Elderly (>=65 years)

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

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)

Dopo il completamento dello studio di 3 anni, ai soggetti dello studio verrà chiesto di entrare in uno studio separato di 5 anni di follow-up a lungo termine (LTFU) per continuare a monitorare la sicurezza e l'efficacia fino a 8 anni dopo la somministrazione dell'IMP.

After having completed of the 3-year study,, the study subjects will be asked to enter in a separate 5-years Long Term Follow-Up (LTFU) study to keep on monitoring safety and efficacy until 8 years post IMP administration.

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

2023-06-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-10-12

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

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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