Clinical Trials Register

Summary
EudraCT Number:	2020-000535-45
Sponsor's Protocol Code Number:	PQ-110-005
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:	2021-08-17
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-000535-45

A.3

Full title of the trial

An Open-Label, Dose Escalation and Double-Masked, Randomized, Controlled Study to Evaluate the Safety and Tolerability of Sepofarsen in Pediatric Subjects <8 Years of Age with Leber Congenital Amaurosis Type 10 (LCA10) due to the c.2991 +1655A>G (p.Cys998X) mutation

Studio in aperto, controllato, randomizzato, con incremento della dose e in doppio cieco volto a valutare la sicurezza e la tollerabilità di sepofarsen in soggetti pediatrici di età <8 anni affetti da amaurosi congenita di Leber di tipo 10 (LCA10) dovuta alla mutazione c.2991+1655A>G (p.Cys998X)

A.3.1

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

Study to test the safety and tolerability of different doses (amounts) of sepofarsen (an RNA therapy) in children less than 8 years that have CEP290 mediated Leber Congenital Amaurosis 10 (LCA10) due to the c.2991+1655A>G mutation

Studio per testare la sicurezza e tollerabilitá di differenti dosi (quantitá) di sepofarsen (una terapia a RNA) in bambini di etá inferiore a 8 anni che hanno Amaurosi Congenita di Leber 10 (LCA10) mediata da CEP290 dovuta alla mutazione c.2991+1655A>G (p.Cys998X)

A.3.2

Name or abbreviated title of the trial where available

Brighten

A.4.1

Sponsor's protocol code number

PQ-110-005

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/129/2021

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	0031620180945
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	Sepofarsen
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.3.9.4	EV Substance Code	SUB199409
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.3.8 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.3.9.4	EV Substance Code	SUB199409
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.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 Congenital Amaurosis 10 (LCA10) due to c.2991+1655A>G mutation (p.Cys998X) in the CEP290 Gene

Amaurosi Congenita di Leber 10 (LCA10) dovura alla mutazione c.2991+1655A>G (p.Cys998X) nel gene CEP290

E.1.1.1

Medical condition in easily understood language

LCA10 due to a specific mutation in the CEP290 gene called c.2991+1655A>G or p.Cys998X

LCA10 dovuta ad una specifica mutazione nel gene CEP290 chiamata c.2991+1655A>G o p.Cys998X

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

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 of the study is to evaluate safety and tolerability of sepofarsen in pediatric subjects aged <8 years

L'obiettivo primario dello studio é la valutazione della sicurezza e tollerabilità di sepofarsen in soggetti pediatrici <8 anni di età.

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are to evaluate the effect of sepofarsen on structural and functional ophthalmic outcome measures.

Gli obiettivi secondari dello studio sono la valutazione dell’effetto di sepofarsen sulle misure di esito oftalmico strutturale e funzionale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female child, <8 years of age at Screening
2. A clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in the CEP290 gene, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are acceptable with Sponsor approval.
3. Best corrected visual acuity (BCVA) equal to or better than Light Perception, and equal to or worse than approximate Snellen equivalent 20/50 in the treatment eye.
4. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as determined by the Investigator

1. Bambini di sesso maschile o femminile, di età <8 anni allo Screening
2. Una diagnosi clinica di LCA e una diagnosi molecolare di omozigosi o eterozigosi composta per la mutazione c.2991+1655A>G nel gene CEP290, in base all’analisi di genotipizzazione allo Screening. Con l’approvazione dello Sponsor, un referto anamnestico di genotipizzazione di un laboratorio certificato è considerato accettabile.
3. Migliore acuità visiva corretta (BCVA) uguale o superiore alla percezione della luce, e uguale o peggiore rispetto all'equivalente di Snellen approssimativo 20/50 nell’occhio di trattamento.
4. Mezzi diottrici trasparenti e dilatazione pupillare adeguata per consentire un imaging retinico di buona qualità, come determinato dallo Sperimentatore.

E.4

Principal exclusion criteria

1.Presence of additional homozygous or compound heterozygous pathogenic mutations (other than the c.2991+1655A>G mutation in the CEP290 gene) in genes associated with other recessive inherited retinal degenerative diseases or syndromes (eg, Usher syndrome) based on genetic analysis.
2.Presence of (likely) pathogenic mutations in genes associated with dominant or X-linked inherited retinal degenerative diseases or syndromes (eg. autosomal dominant retinitis pigmentosa, X-linked Retinoschisis) based on genetic analysis.
3.Presence of any significant ocular or non-ocular disease/disorder (including lab/medication 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 trial, may influence the results of the trial, or the subject’s ability to participate in the trial. 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 treatment eye.
4.History or presence of ocular herpetic diseases (including herpes simplex virus, varicella zoster or cytomegalovirus) in the treatment eye.
5.Presence of any active ocular infection in either eye.
6.Presence of any of the following lens opacities in the treatment eye: cortical opacity = +2, posterior subcapsular opacity = +2, or a nuclear sclerosis = +2, and which: 1) is clinically significant in the opinion of the Investigator, or 2) would adequately prevent clinical and photographic evaluation of the retina.
7.Receipt within 1 month 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 trial. Subjects who received an intraocular or periocular surgery between 1 to 3 months prior Screening, may only be considered for inclusion (at the discretion of the Investigator) if there are no clinically significant complications of surgery present.
8.Current treatment or treatment within the past 12 months with therapies known to influence the immune system (including but not limited to cytostatics, interferons, TNF-binding proteins, drugs acting on immunophilins, or antibodies with known impact on the immune system). Subjects that have been treated with systemic steroids within the past 12 months or that require intermittent use of topical steroids may be considered for inclusion based on Investigator judgement, dependent on the status of the underlying disease.
9.Current treatment or treatment within the past 3 months or planned treatment with drugs known to be toxic to the lens, retina, or the optic nerve including, but not limited to, systemic/intraocular steroids, amiodarone, desferrioxamine/desferoxamine, chloroquine/hydroxychloroquine sulfate (Plaquenil), tamoxifen, ethambutol, phenothiazine derivatives including chlorpromazine, fluphenazine (decanoate), levomepromazine, and thioridazine.
10.A history of glaucoma in the treatment eye or raised intraocular pressure in the treatment eye that is not controlled with medication at the time of Screening.
11.Use of any investigational drug or device within 3 months or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the trial period.
12.Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.

1. Presenza di ulteriori mutazioni patogene omozigoti o eterozigoti composte (diverse dalla mutazione c.2991+1655A>G nel gene CEP290) in geni associati ad altre malattie o sindromi degenerative retiniche ereditarie recessive (ad es. sindrome di Usher) in base all’analisi genetica.
2. Presenza di (probabili) mutazioni patogene in geni associati a malattie o sindromi degenerative retiniche ereditarie dominanti o legate all’X (ad es. retinite pigmentosa autosomica dominante, retinoschisi legata all’X) in base all’analisi genetica.
3. Presenza di qualsiasi malattia/disturbo oculare o non oculare significativi (incluse anomalie di laboratorio/farmaci) che, a giudizio dello Sperimentatore e Medical Monitor, potrebbe mettere il soggetto a rischio a causa della partecipazione alla sperimentazione, potrebbe influenzare i risultati della sperimentazione o la capacità del soggetto di partecipare alla sperimentazione. Ciò include, a titolo esemplificativo ma non esaustivo, un soggetto che: 1) non è un candidato idoneo per il trattamento con oligonucleotidi antisenso, 2) presenta edema maculare cistoide (EMC) concomitante nell’occhio di trattamento.
4. Anamnesi o presenza di malattie erpetiche oculari (tra cui virus herpes simplex, varicella zoster o citomegalovirus) nell’occhio di trattamento.
5. Presenza di qualsiasi infezione oculare attiva in entrambi gli occhi.
6. Presenza di una qualsiasi delle seguenti opacità del cristallino nell’occhio di trattamento: opacità corticale = +2, opacità sottocapsulare posteriore = +2, o sclerosi nucleare = +2, e che: 1) sia clinicamente significativa secondo il parere dello Sperimentatore, o 2) impedirebbe sufficientemente la valutazione clinica e fotografica della retina.
7. Essersi sottoposti entro 1 mese prima dello Screening a qualsiasi intervento chirurgico intraoculare o perioculare (compresa la chirurgia refrattiva) o un’iniezione IVT o un intervento chirurgico o una procedura intraoculari programmati nel corso della sperimentazione. I soggetti che hanno ricevuto un intervento chirurgico intraoculare o perioculare tra 1 e 3 mesi prima dello Screening possono essere presi in considerazione per l’inclusione (a discrezione dello Sperimentatore) solo se non sono presenti complicanze clinicamente significative dell’intervento chirurgico.
8. Trattamento attuale o negli ultimi 12 mesi con terapie che è noto influenzino il sistema immunitario (tra cui, a titolo esemplificativo ma non esaustivo, citostatici, interferoni, proteine leganti il TNF, farmaci che agiscono su immunofiline o anticorpi con impatto noto sul sistema immunitario). I soggetti che sono stati trattati con steroidi sistemici negli ultimi 12 mesi o che richiedono l’uso intermittente di steroidi topici possono essere presi in considerazione per l’inclusione in base al giudizio dello Sperimentatore, a seconda dello stato della malattia sottostante.
9. Trattamento attuale o negli ultimi 3 mesi o trattamento programmato con farmaci la cui tossicità per il cristallino, la retina o il nervo ottico è nota, inclusi, a titolo esemplificativo ma non esaustivo, steroidi sistemici/intraoculari, amiodarone, desferrioxamina/desferoxamina, clorochina/idrossiclorochina solfato (Plaquenil), tamoxifene, etambutolo, fenotiazinici tra cui clorpromazina, flufenazina (decanoato), levomepromazina e tioridazina.
10. Anamnesi di glaucoma nell’occhio di trattamento o aumento della pressione intraoculare nell’occhio di trattamento non controllato con farmaci al momento dello Screening.
11. Uso di qualsiasi farmaco o dispositivo sperimentale entro 3 mesi o 5 emivite del Giorno 1, a seconda di quale periodo sia più lungo, o l’intenzione di partecipare a un altro studio su un farmaco o un dispositivo durante il periodo della sperimentazione.
12. Qualsiasi precedente trattamento con terapia genetica o con cellule staminali per malattia oculare o non oculare.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoints are:
• Incidence and severity of ocular AEs
• Incidence and severity of non-ocular AEs

Gli endpoint primari sono:
• Incidenza e gravità degli eventi avversi (EA) oculari
• Incidenza e gravità degli EA non oculari.

E.5.1.1

Timepoint(s) of evaluation of this end point

Until 24 months after IVT injection

Fino a 24 mesi dopo l'iniezione IVT

E.5.2

Secondary end point(s)

Secondary endpoints are:
• Best-corrected visual acuity (BCVA)
• Retinal sensitivity measured by Full-field stimulus threshold testing (FST) (white, red, and blue)

Gli endopoint secondari sono:
• BCVA
• Sensibilità retinica misurata mediante FST (bianco, rosso e blu)

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months
Change from baseline values for these endpoints will also be assessed at other time points.

12 mesi
La modifica dai valori al baseline per questi endopint saranno anche valutati ad altri time point.

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

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

Tollerabilitá

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

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

European Union

United Kingdom

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

LSLV

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)

F.1.2

Adults (18-64 years)

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

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. Sará richiesto consenso dei genitori/tutore legale.

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 comlpetano lo studio e traggono beneficio terapeutico, lo Sponsor prevede l'accesso continuato al farmaco di studio fino a registrazione del farmaco, finché il rapporto rischio/beneficio continui ad essere 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

2021-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-06-09

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials