Clinical Trials Register

Summary
EudraCT Number:	2018-003501-25
Sponsor's Protocol Code Number:	PQ-110-003
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-01-21
Trial results	View 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

2018-003501-25

A.3

Full title of the trial

A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety, Tolerability and Systemic Exposure of QR-110 in Subjects with Leber's Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Studio randomizzato, in doppio cieco, controllato, multidose per valutare l’efficacia, la sicurezza, la tollerabilità e l’esposizione sistemica di QR-110 in soggetti affetti da amaurosi congenita di Leber (LCA) dovuta alla mutazione c.2991+1655A>G (p.Cys998X) nel gene CEP290

A.3.1

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

Study to evaluate the efficacy, safety, tolerability and the extent to which the study drug is distributed in the body of multiple doses of QR-110 in subjects with LCA10 compared to a sham procedure. The study will be double-masked, randomized and controlled which means that both patients and study staff will not know and cannot influence who receives which treatment (study drug of sham).

Studio per valutare l'efficacia, la sicurezza, la tollerabilità e la misura in cui il farmaco in studio è distribuito nel corpo di dosi multiple di QR-110 in soggetti con LCA10 rispetto a una procedura simulata. Lo studio sarà in doppio cieco, randomizzato e controllato, il che significa che sia i pazienti che il personale dello studio non sapranno e non potranno influenzare chi riceve quale trattamento (farmaco in studio o simulato).

A.3.2

Name or abbreviated title of the trial where available

Illuminate

A.4.1

Sponsor's protocol code number

PQ-110-003

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	PROQR THERAPEUTICS N.V.
B.1.3.4	Country	Netherlands
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	ProQR Therapeutics
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ProQR Therapeutics
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Zernikedreef 9
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CK
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+310620180945
B.5.5	Fax number	012345
B.5.6	E-mail	clinical@proqr.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/3/16/1641
D.3 Description of the IMP
D.3.1	Product name	QR-110
D.3.2	Product code	[QR-110]
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sepofarsen
D.3.9.1	CAS number	2227173-68-2
D.3.9.2	Current sponsor code	QR-110
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3200
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/3/16/1641
D.3 Description of the IMP
D.3.1	Product name	QR-110
D.3.2	Product code	[QR-110]
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sepofarsen
D.3.9.1	CAS number	2227173-68-2
D.3.9.2	Current sponsor code	QR-110
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	800
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: 3
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/3/16/1641
D.3 Description of the IMP
D.3.1	Product name	QR-110
D.3.2	Product code	[QR-110]
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sepofarsen
D.3.9.1	CAS number	2227173-68-2
D.3.9.2	Current sponsor code	QR-110
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1600
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: 4
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/3/16/1641
D.3 Description of the IMP
D.3.1	Product name	QR-110
D.3.2	Product code	[QR-110]
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sepofarsen
D.3.9.1	CAS number	2227173-68-2
D.3.9.2	Current sponsor code	QR-110
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	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.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

Leber's Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Amaurosi congenita di Leber (LCA) dovuta alla mutazione c.2991+1655A>G (p.Cys998X) nel gene CEP290

E.1.1.1

Medical condition in easily understood language

LCA due to the p.Cys998X mutation in the CEP290 gene (LCA10)

LCA dovuta alla mutazione p.Cys998X nel gene CEP290 (LCA 10)

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	10070667
E.1.2	Term	Leber's congenital amaurosis
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

The primary objective is to evaluate the efficacy of QR-110 administered by intravitreal (IVT) injection in subjects with LCA due to the CEP290 p.Cys998X mutation

Valutare l’efficacia di QR-110 somministrato mediante iniezione intravitreale (IVT) in soggetti affetti da LCA dovuta alla mutazione p.Cys998X del gene CEP290.

E.2.2

Secondary objectives of the trial

The secondary objectives are to evaluate:
- The safety and tolerability of QR-110 administered via IVT injection in subjects with LCA due to the CEP290 p.Cys998X mutation
- Changes in quality of life in subjects with LCA due to the CEP290 p.Cys998X mutation treated with QR-110
- The systemic exposure of QR-110 administered by IVT injection in subjects with LCA due to the CEP290 p.Cys998X mutation

Gli obiettivi secondari sono per valutare:
-La sicurezza e la tollerabilità di QR-110 somministrato mediante iniezione IVT in soggetti affetti da LCA dovuta alla mutazione p.Cys998X del gene CEP290.
- I cambiamenti nella qualità della vita nei soggetti affetti da LCA dovuta alla mutazione p.Cys998X del gene CEP290 trattati con QR-110.
-L'’esposizione sistemica a QR-110 somministrato mediante iniezione intravitreale (IVT) in soggetti affetti da LCA dovuta alla mutazione p.Cys998X del gene CEP290.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Relating to Study Initiation : The subject is eligible for the study and thus eligible to receive QR-110 or sham-procedure in the treatment eye (ie, the first eye to be treated) if all the following inclusion criteria apply at Screening/Day 1:
1. An adult ( = 18 years) willing and able to provide informed consent for participation -OR- a minor (8 to < 18 years) with a parent or legal guardian willing and able to provide written permission for the subject's participation prior to performing any study related procedures and pediatric subjects able to provide age appropriate assent for study participation.
2. Male or female, > 8 years of age at screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are acceptable with Sponsor approval.
3. BCVA better or equal to Logarithm of the Minimum Angle of Resolution (logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate Snellen equivalent 20/50) in the treatment eye, using the best BCVA reading at Screening and based on the Early Treatment Diabetic Retinopathy Study (ETDRS) or the Berkeley Rudimentary Vision Test (BRVT).
4. Detectable outer nuclear layer (ONL) in the area of the macula as determined by the Investigator at Screening.
5. An electroretinogram (ERG) result consistent with LCA, as determined by the Investigator. A historic ERG result may be acceptable for eligibility.
6. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.
7. Non-pregnant and non-breastfeeding subjects.

Relating to Treatment Initiation Contralateral Eye:
1. BCVA better or equal to Logarithm of the Minimum Angle of Resolution (logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate Snellen equivalent 20/50) in the contralateral eye, using the best BCVA reading at Month 12 (see Section 8.1) and based on the Early Treatment Diabetic Retinopathy Study (ETDRS) or the Berkeley Rudimentary Vision Test (BRVT).
2. Detectable outer nuclear layer (ONL) in the area of the macula of the contralateral eye as determined by the Investigator.
3. Clear ocular media and adequate pupillary dilation to permit goodquality retinal imaging in the contralateral eye, as assessed by the Investigator.
4. Non-pregnant and non-breastfeeding subjects.

Relativo all'avvio dello studio: il soggetto è idoneo allo studio e quindi idoneo a ricevere QR-110 o procedura sham nell'occhio del trattamento (ovvero il primo occhio da trattare) se tutti i seguenti criteri di inclusione si applicano allo Screening/Giorno 1 :
1. Un adulto ( = 18 anni) disposto e in grado di fornire il consenso informato per la partecipazione -OPPURE- un minorenne (da 8 a <18 anni) con un genitore o tutore legale disposto e in grado di fornire l'autorizzazione scritta per la partecipazione del soggetto prima di eseguire qualsiasi procedura correlata allo studio e soggetti pediatrici in grado di fornire un assenso adeguato all'età per la partecipazione allo studio.
2. Maschio o femmina, > 8 anni allo screening con una diagnosi clinica di LCA e una diagnosi molecolare di omozigosi o eterozigosi composta per la mutazione CEP290 p.Cys998X, basata sull'analisi di genotipizzazione allo Screening. I risultati storici di genotipizzazione di un laboratorio certificato sono accettabili con l'approvazione dello sponsor.
3. BCVA migliore o uguale al logaritmo dell'angolo minimo di risoluzione (logMAR) +3.0 (movimento della mano), e uguale o peggiore di logMAR + 0,4 (equivalente di Snellen approssimativo 20/50) nell'occhio del trattamento, utilizzando la migliore lettura BCVA allo screening e basato sullo studio sulla retinopatia diabetica per trattamento precoce (ETDRS) o sul test di visione rudimentale di Berkeley (BRVT).
4. Rilevamento dello strato nucleare esterno (ONL) nell'area della macula, come determinato dallo sperimentatore allo screening.
5. Un risultato elettroretinogramma (ERG) coerente con LCA, come determinato dall'Investigatore. Un risultato ERG storico può essere accettabile per l'idoneità.
6. Chiari mezzi oculari e adeguata dilatazione pupillare per consentire immagini retiniche di buona qualità, come valutato dallo sperimentatore.
7. Soggetti non in gravidanza e non in allattamento.

In relazione all'occhio controlaterale di inizio del trattamento:
1. BCVA migliore o uguale al logaritmo dell'angolo minimo di risoluzione (logMAR) +3.0 (movimento della mano), e uguale o peggiore di logMAR + 0,4 (equivalente di Snellen approssimativo 20/50) nell'occhio controlaterale, utilizzando la migliore lettura BCVA al Mese 12 (vedere Sezione 8.1) e basato sullo Studio sulla retinopatia diabetica per trattamento precoce (ETDRS) o sul Test di visione rudimentale di Berkeley (BRVT).
2. Strato nucleare esterno rilevabile (ONL) nell'area della macula dell'occhio controlaterale determinato dall'Investigatore.
3. Chiari mezzi oculari e adeguata dilatazione pupillare per consentire una buona imaging della retina nell'occhio controlaterale, come valutato dallo sperimentatore.
4. Soggetti non in gravidanza e non in allattamento.

E.4

Principal exclusion criteria

Relating to Study Initiation : The subject is ineligible for the study if any of the following criteria apply at Screening/Day 1:
1. Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study.
2. Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the study period.
3. Any prior receipt of genetic or stem-cell therapy for ocular or non ocular disease.
4. Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the study.
5. Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
6. Pregnant and breastfeeding subjects.
Relating to Treatment Initiation Contralateral Eye:
1. Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study. This includes but is not limited a subject who: 1) is not an appropriate candidate for antisense oligonucleotide treatment, 2) has concurrent cystoid macular edema (CME) in the contralateral eye.
2. A planned IVT injection or intraocular or periocular surgery/procedure (including refractive surgery) in the contralateral eye during the course of the study.
3. Plans to participate in another study of a drug or device during the study period.
4. Pregnant and breastfeeding subjects.

Relativo all'avvio dello studio: il soggetto non è elegibile per lo studio se uno dei seguenti criteri si applica allo screening/giorno 1:
1. Presenza di qualsiasi patologia / disturbo oculare o non oculare significativo (comprese le anomalie dei farmaci e dei test di laboratorio) che, secondo l'opinione del medico e con il consenso del Medical Monitor, possono mettere a rischio il soggetto a causa della partecipazione allo studio, può influenzare i risultati dello studio o la capacità del soggetto di partecipare allo studio.
2. L'uso di qualsiasi farmaco o dispositivo sperimentale entro 90 giorni o 5 emivite al giorno 1, a seconda di quale sia il periodo più lungo, o preveda di partecipare a un altro studio di un farmaco o dispositivo durante il periodo di studio.
3. Qualsiasi precedente ricevimento di terapia genetica o di cellule staminali per malattia oculare o non oculare.
4. ha ricevuto entro 3 mesi prima dello screening qualsiasi intervento chirurgico intraoculare o perioculare (inclusa la chirurgia refrattiva), o di un'iniezione di IVT o di un intervento chirurgico o di una procedura intraoculare pianificata nel corso dello studio.
5. Ipersensibilità nota agli oligonucleotidi antisenso o ad eventuali componenti dell'iniezione.
6. Soggetti in gravidanza e in allattamento.
In relazione all'occhio controlaterale di inizio del trattamento:
1. Presenza di qualsiasi patologia / disturbo oculare o non oculare significativo (comprese le anomalie dei farmaci e dei test di laboratorio) che, secondo l'opinione del medico e con il consenso del Medical Monitor, possono mettere a rischio il soggetto a causa della partecipazione al studio, può influenzare i risultati dello studio o la capacità del soggetto di partecipare allo studio. Ciò include ma non è limitato un soggetto che: 1) non è un candidato appropriato per il trattamento con oligonucleotidi antisenso, 2) ha concomitante edema maculare cistoide (CME) nell'occhio controlaterale.
2. Iniezione IVT pianificata o chirurgia / procedura intraoculare o perioculare (compresa la chirurgia refrattiva) nell'occhio controlaterale durante il corso dello studio.
3. Prevede di partecipare a un altro studio su un farmaco o dispositivo durante il periodo di studio.
4. Soggetti in gravidanza e in allattamento.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is mean change from baseline in BCVA (based on ETDRS and/or BRVT) at 12 months of treatment versus sham

Variazione media dal valore basale della BCVA (sulla base di ETDRS e/o BRVT) a 12 mesi di trattamento rispetto alla procedura simulata

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 mesi

E.5.2

Secondary end point(s)

Key secondary : Change from baseline in mobility course score at 12
months of treatment versus sham, as assessed by a masked central
reader
Secondary endpoints :
• Change from baseline in BCVA:
o By = 3 lines (or = 0.3 logMAR change) in subjects with BCVA equal to
or better than 1.7 logMAR at baseline
o By a clinically meaningful improvement in subjects with BCVA worse
than 1.7 logMAR at baseline
• Change from baseline in mobility course score
• Change from baseline in BCVA based on Freiburg Visual Acuity Test
(FrACT)
• Change from baseline in light sensitivity to FST (white, red, and blue)
• Change from baseline in ellipsoid zone (EZ) width/area assessed by
spectral domain optical coherence tomography SD-OCT
• Change from baseline in low luminance visual acuity (LLVA)
• Change from baseline in oculomotor instability
• Change from baseline as determined by fundus autofluorescence (FAF)
imaging
• Change from baseline as determined by microperimetry
• Change from baseline in PRO measures, as measured by:
o The Visual Function Questionnaire-25 (VFQ-25) score (adult subjects)
o The Cardiff Visual Ability Questionnaire for Children (CVAQC) (pediatric
subjects)
o the Patient Global Impressions of Severity (PGI S)
o the Patient Global Impressions of Change (PGI C)
• Systemic exposure to QR-110
• Ocular and non-ocular AEs

Secondari principali: variazione rispetto al basale del punteggio del mobility course a 12 mesi di trattamento contro sham, come valutato da una lettore centrale masked
Endpoint secondari:
• Modifica rispetto al basale in BCVA:
o Di = 3 righe (o = 0,3 logMAR change) in soggetti con BCVA uguale a
o migliore di 1,7 logMAR al basale
o Con un miglioramento clinicamente significativo nei soggetti con BCVA peggiore di 1,7 logMAR al basale
• Modifica rispetto al basale del punteggio del mobility course
• Modifica rispetto al basale in BCVA in base al test dell'acuità visiva di Friburgo (Fract)
• Passaggio dalla linea di base della sensibilità alla luce a FST (bianco, rosso e blu)
• Variazione rispetto alla base della larghezza / area della zona dell'ellissoide (EZ) valutata da tomografia a coerenza ottica a dominio spettrale SD-OCT
• Variazione dalla linea di base nell'acuità visiva a bassa luminanza (LLVA)
• Variazione rispetto all'instabilità dell'instabilità oculomotoria
• Variazione rispetto al basale determinata dall'autofluorescenza del fondo oculare (FAF)
• Variazione rispetto al basale determinata dalla microperimetria
• Variazione rispetto al basale delle misure PRO, misurata da:
o Il punteggio Visual Function Questionnaire-25 (VFQ-25) (soggetti adulti) o Il Cardiff Visual Ability Questionnaire for Children (CVAQC) (soggetti pediatrici)
o the Patient Global Impressions of Severity (IGP S)
o the Patient Global Impressions of Change (IGP C)
• Esposizione sistemica a QR-110
• eventi avversi oculari e non oculari

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

24 mesi

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

Tolerability

Tollerabilità

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)

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Comparatore 1: dose dell'IMP livello 2; Comparatore 2: iniezione IVT simulata (no somministrazione I

Comparator 1: dose level 2 IMP; Comparator 2: Sham IVT injection (no IMP administration)

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

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

Brazil

Canada

United States

European Union

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minors. Parental/legal guardian consent will be requested.

Minori. Il consenso dei genitori/tutore legale sarà richiesto

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)

For subjects completing the study and deriving therapeutic benefit, the Sponsor plans on providing continued access to the study drug until drug registration, as long as the benefit/risk continues to be positive.

Per i soggetti che completano lo studio e ne traggono beneficio terapeutico, lo Sponsor intende continuare a fornire il farmaco dello studio fino alla registrazione, fintanto che il rischio/beneficio continui a rimanere positivo.

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

2020-09-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-09-09

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