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    Summary
    EudraCT Number:2021-002729-74
    Sponsor's Protocol Code Number:PQ-421a-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:2022-01-17
    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.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2021-002729-74
    A.3Full title of the trial
    A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety and Tolerability of QR-421a in Subjects with Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene with Advanced Vision Loss
    Uno studio in doppio cieco, randomizzato, controllato, a dose multipla, per valutare l’efficacia, la sicurezza e la tollerabilità di QR-421a in soggetti con retinite pigmentosa (RP) dovuta a mutazioni nell’esone 13 del gene USH2A con perdita di visione avanzata
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2/3 study to evaluate efficacy, safety, and tolerability of QR-421a in subjects with advanced vision loss
    Uno studio di fase 2/3 per valutare l’efficacia, la sicurezza e la tollerabilità di QR-421a in soggetti con perdita di visione avanzata
    A.3.2Name or abbreviated title of the trial where available
    Sirius
    Sirius
    A.4.1Sponsor's protocol code numberPQ-421a-003
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05158296
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPROQR THERAPEUTICS N.V.
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportProQR Therapeutics
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationProQR Therapeutics IV B.V.
    B.5.2Functional name of contact pointClinical Trial Manager
    B.5.3 Address:
    B.5.3.1Street AddressZernikedreef 9
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333CK
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031881667000
    B.5.6E-mailinfo@proqr.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/1973
    D.3 Description of the IMP
    D.3.1Product nameQR-421a
    D.3.2Product code [QR-421a]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravitreal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeQR-421a
    D.3.9.3Other descriptive nameQR-421a is a single stranded, synthetic, chemically modified, antisense oligonucleotide consisting of 2'-O-(2-methoxyethyl) ribonucleosides with a phosphorothioate backbone
    D.3.9.4EV Substance CodeSUB193950
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/1973
    D.3 Description of the IMP
    D.3.1Product nameQR-421a
    D.3.2Product code [QR-421a]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravitreal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeQR-421a
    D.3.9.3Other descriptive nameQR-421a is a single stranded, synthetic, chemically modified, antisense oligonucleotide consisting of 2'-O-(2-methoxyethyl) ribonucleosides with a phosphorothioate backbone
    D.3.9.4EV Substance CodeSUB193950
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another 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.1.1Medical condition(s) being investigated
    Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene
    Retinite Pigmentosa (RP) dovuta a mutazioni nell'Esone 13 del Gene USH2A
    E.1.1.1Medical condition in easily understood language
    RP due to Mutations in Exon 13 of the USH2A Gene
    RP dovuta a mutazioni nell'Esone 13 del Gene USH2A
    E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10038914
    E.1.2Term Retinitis pigmentosa
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10038914
    E.1.2Term Retinitis pigmentosa
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of QR-421a
    Valutare l'efficacia di QR-421a
    E.2.2Secondary objectives of the trial
    To further evaluate efficacy
    To evaluate the safety and tolerability of QR-421a
    To evaluate changes in Patient-Reported Outcome (PRO) measures in subjects treated with QR-421a
    To evaluate systemic exposure of QR-421a
    Valutare ulteriormente l’efficacia
    Valutare la sicurezza e la tollerabilità di QR-421a
    Valutare le variazioni nelle misure degli esitiriferiti dai pazienti (PRO) nei soggetti trattati con QR-421a
    Valutare l’esposizione sistemica a QR-421a
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - An adult (= 18 years) willing and able to provide informed consent for participation prior to performing any study related procedure. OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions, and attend study visits with the subject as required.
    - Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
    - A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis at screening.
    - Reliable BCVA, perimetry, and other measurements in both eyes.
    -Un adulto (=18 anni) disposto a e in grado di fornire il consenso informato alla partecipazione prima dell’esecuzione di qualsiasi procedura correlata allo studio. OPPURE
    Un minore (12 - <18 anni) disposto a e in grado di completare tutte le valutazioni dello studio e di rispettare il protocollo, con un genitore o tutore disposto e in grado di seguire le istruzioni dello studio e di presentarsi alle visite dello studio con il soggetto come richiesto.
    - Presentazione clinica compatibile con la RP con sindrome di Usher di tipo 2 o forma non sindromica di RP (NSRP) in base alle valutazioni oftalmiche, audiologiche e vestibolari.
    - Una diagnosi molecolare di omozigosità o eterozigosità composta di 1 o più mutazioni patogene dell’esone 13 nel gene USH2A in base all’analisigenetica allo screening.
    -BCVA, perimetria e altre valutazioni attendibili in entrambi gli occhi
    E.4Principal exclusion criteria
    - Presence of any significant ocular or non-ocular disease/disorder (or medication and/or 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.
    - Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
    -La presenza di malattia/disturbo oculare o non oculare significativo (o farmaci e/o anomalie nei test di laboratorio) che, secondo il parere dello sperimentatore e in accordo con il responsabile Medico, può porre il soggetto a rischio a causa della partecipazione allo studio, influenzare i risultati dello studio o la capacità del soggetto di partecipare allo studio.
    - Nota Ipersensibilità agli oligonucleotidi antisenso o ai componenti dell’iniezione.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in best corrected visual acuity (BCVA) (based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart) at 18 months of treatment versus sham-procedure
    Variazione rispetto al basale della migliore acuità visiva corretta (BCVA) [in base alla tavola Early Treatment Diabetic Retinopathy Study (ETDRS)] a 18 mesi dal trattamento rispetto alla procedura simulata (di controllo)
    E.5.1.1Timepoint(s) of evaluation of this end point
    At multiple timepoints up to 18 months
    A diversi timepoints, fino a 18 mesi
    E.5.2Secondary end point(s)
    Key Secondary endpoints:

    - Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters (ETDRS)

    Other Secondary endpoints:
    - Change from baseline in the following outcome measures:
    Other measures of BCVA
    Spectral domain optical coherence tomography (SD-OCT)
    Low Luminance Visual Acuity (LLVA)
    Microperimetry
    Static perimetry
    Full-field Stimulus Threshold (FST)
    -Change from baseline in PRO measures, as assessed by:
    Veteran Administration Low Vision Visual Functioning Questionnaire (VA LV VFQ-20) (Stelmack 2007)
    Patient Global Impressions of Severity (PGI-S)
    Patient Global Impressions of Change (PGI-C)
    -Ocular and non-ocular adverse events (AEs)
    -Exposure of QR-421a in serum
    Endpoint secondari Principali:
    -Percentuale di pazienti che mantengono la vista definita dalla perdita di BCVA inferiore a 15 lettere (ETDRS)

    Altri endpoint secondari
    -Variazione rispetto al basale nelle seguentimisure di esito:
    o Altre misure di BCVA
    o Tomografia a coerenza ottica nel dominio spettrale (SD-OCT)
    o Acuità visiva a bassa luminanza (LLVA)
    o Microperimetria
    o Perimetria statica
    o Soglia di stimolo a pieno campo (FST)
    -Variazione rispetto al basale nelle misure PRO, come valutato tramite:
    o Veteran Administration Low Vision Visual Functioning Questionnaire (VA LV VFQ-20) (Stelmack 2007)
    o Patient Global Impressions of Severity (PGI-S)
    o Patient Global Impressions of Change (PGI-C)
    -Eventi avversi oculari e non oculari
    -Esposizione a QR-421 nel siero
    E.5.2.1Timepoint(s) of evaluation of this end point
    At multiple timepoints up to 24 months
    A diversi timepoints fino a 24 mesi
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilità
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Studio a dose multipla
    Multiple-Dose Study
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Procedura simulata
    Sham
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Brazil
    Canada
    European Union
    United Kingdom
    United States
    E.8.7Trial 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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 74
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 27
    F.4.2.2In the whole clinical trial 81
    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 plans on providing access to study drug after the end of study (EOS) in an open-label extension study if the benefit:risk is deemed to be positive
    Lo Sponsor prevede di fornire accesso al farmaco in studio alla fine dello studio (EOS) in uno studio di estensione in aperto, se il rischio beneficio sarà ritenuto positivo
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-05-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-07-28
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-08-11
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