Clinical trial • Phase III • Neurology
ZOREVUNERSEN SODIUM for Dravet syndrome
Phase III trial of ZOREVUNERSEN SODIUM for Dravet syndrome. Randomised, sham (sham control procedure).. 150 participants.
Overview
- Trial Therapeutic Area
- Neurology
- Trial Disease
- Dravet syndrome
- Trial Stage
- Phase III
- Drug Modality
- Oligonucleotide
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 17-02-2025
- First CTIS Authorization Date
- 30-06-2025
Trial design
Randomised, sham (sham control procedure). Phase III trial across 30 sites in Sweden, Poland, Spain and others.
- Randomised
- Yes
- Comparator
- Sham (sham control procedure).
- Target Sample Size
- 150
- Trial Duration For Participant
- 364
Eligibility
Recruits 150 paediatric patients.
- Vulnerable Population
- Paediatric population selected (patients ≥2 and <18 years). Consent/assent handling: patient and/or authorized representative must be willing and able to give informed consent/assent; caregiver involvement required for protocol compliance. Study-specific parental/legal guardian ICFs and age-appropriate assent forms are provided (including assent for older children/teens, parental/legal guardian ICFs, additional caregiver ICFs, and documents for participants turning 18). eConsent materials and translated documents are available for country-specific use.
Inclusion criteria
- {"criterion_text":"-Patient and/or authorized representative must be willing and able to give informed consent/assent and any authorizations required by local law for participation in the study."}
- {"criterion_text":"-Patient and their caregiver must be willing and able (in the Investigator’s opinion) to comply with all protocol requirements."}
- {"criterion_text":"-At signing of consent/assent, patient must be ≥2 and <18 years of age."}
- {"criterion_text":"-Patient must have a clinical diagnosis of DS confirmed by the Epilepsy Study Consortium, Inc. (ESCI) and as defined by: Onset, prior to 12 months of age, of recurrent focal with motor signs, hemiclonic, or generalized tonic-clonic seizures, which are often prolonged and triggered by hyperthermia. No past history of causal magnetic resonance imaging (MRI) lesion (past MRI or study-associated MRI not required to confirm absence of lesion). No other known etiology causing clinical DS manifestations. Normal development at seizure onset."}
- {"criterion_text":"-Patient must have a documented pathogenic, likely pathogenic variant, or variant of uncertain significance in the sodium voltage-gated channel type 1 alpha subunit (SCN1A) gene. Patients who have SCN1A testing results of Negative (no variants identified) cannot be randomized."}
- {"criterion_text":"-Experiences the required number of major motor seizures during the 6-week Observation Period. Seizure types included in counts are Hemiclonic, Focal with Motor Signs, Focal to Bilateral Tonic-Clonic, Generalized Tonic-Clonic, Tonic, Tonic/Atonic (Drop Attacks with fall or risk of fall), and Bilateral Clonic."}
- {"criterion_text":"-Patient must have used at least 2 prior interventions for seizures. These can include anti-seizure medications (ASMs), ketogenic diet and/or vagus nerve stimulation (VNS) with either lack of adequate seizure control or discontinued due to an AE(s). These interventions can be ongoing therapies."}
- {"criterion_text":"-Patient must be taking at least one ASM. Benzodiazepines or ASMs used on a standing basis (i.e., not as needed [PRN]) for any indication will be considered an ASM."}
- {"criterion_text":"-All maintenance ASMs and interventions for seizures (i.e., ketogenic diet or VNS), as well as any marijuana- or cannabinoid-based products, must have been stable (unless adjusted for weight) during the Baseline Period. Felbamate must have been stable (unless adjusted for weight) for at least 6 months prior to Screening Visit A and during the Baseline Period. VNS implantation must have occurred at least 6 months prior to Screening Visit A. Rescue ASMs used on an as needed basis do not need to be stable."}
Exclusion criteria
- {"criterion_text":"-Patient has documented variant in the SCN1A gene associated with gain-of-function potentially including but not limited to: Ala23Glu, Thr162Ile, Arg1636Gln, Thr226Met, Ile236Val, Val250Leu, Leu263Val, Thr398Met, Ala420Val, Val422Leu, Thr1174Ser, Trp1204Arg, Pro1345Ser, Ile1483Met, Gln1489Lys, Ile1498Thr, Ile1498Met, Phe1499Leu, Met1500Val, Arg1575Cys, Val1611Phe, Leu1624Pro, Arg1636Gln, Arg1648Cys, Leu1649Gln, Leu1660Ile, Phe1661Leu, Leu1670Trp, Gly1674Arg, Phe1774Ser, or Asp1866Tyr."}
- {"criterion_text":"-Patient has a diagnostic result in a gene other than SCN1A on the epilepsy gene screening panel. For genes associated with dominant inheritance, one heterozygous pathogenic or likely pathogenic variant is exclusionary. For genes associated with recessive inheritance, biallelic pathogenic or likely pathogenic variant(s) are exclusionary. This includes homozygous variants and compound heterozygous variants. Results consistent with carrier status are not exclusionary."}
- {"criterion_text":"-Patient is currently treated with a maintenance ASM acting primarily as a sodium channel blocker, including but not limited to phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, rufinamide, or cenobamate, given the mechanism of action of zorevunersen."}
- {"criterion_text":"-Patient is currently treated with neuromodulation techniques (e.g., responsive neurostimulation, deep brain stimulation, or transcranial magnetic stimulation), with the exception of VNS."}
- {"criterion_text":"-Patient has emergence of a new seizure type or reemergence of a past seizure type (seizure types that last occurred more than 12 months before Screening Visit A) during the Baseline Period, or has more than 1 hospitalization for seizures during the Baseline Period."}
- {"criterion_text":"-Patient has a spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt. This does not exclude patients with scoliosis or spinal rods if, in the judgement of the Investigator, lumbar puncture can be performed and there is free flow of CSF."}
Endpoints
Primary endpoints
- {"endpoint_text":"-Percent change from baseline in major motor seizure frequency (number per 28 days) in patients receiving zorevunersen as compared with sham from Week 16 to Week 28 (consisting of three 4 week intervals).","definition_or_measurement_approach":"Percent change from baseline in major motor seizure frequency measured as number of major motor seizures per 28 days comparing zorevunersen versus sham between Week 16 and Week 28. Major motor seizures are defined in the protocol as: hemiclonic, focal with motor signs, focal to bilateral tonic-clonic, generalized tonic-clonic, tonic, tonic/atonic (drop attacks with fall or risk of fall), and bilateral clonic."}
Secondary endpoints
- {"endpoint_text":"-Percent change from baseline in major motor seizure frequency (number per 28 days) in patients receiving zorevunersen as compared with sham at each visit from Week 16 to Week 52 (consisting of nine 4 week intervals).","definition_or_measurement_approach":"Percent change from baseline in major motor seizure frequency measured at each visit from Week 16 through Week 52 (nine 4-week intervals); comparisons of zorevunersen versus sham."}
- {"endpoint_text":"-Net treatment benefit across multiple Vineland 3 outcomes, assessed as change from baseline, in patients receiving zorevunersen as compared with sham at Week 52.","definition_or_measurement_approach":"Net treatment benefit evaluated across multiple Vineland-3 outcomes as change from baseline at Week 52 comparing zorevunersen versus sham."}
- {"endpoint_text":"-Change from baseline in subdomain scores on the Vineland-3 in patients receiving zorevunersen as compared with sham at Week 52.","definition_or_measurement_approach":"Change from baseline in Vineland-3 subdomain scores at Week 52 comparing treatment versus sham."}
Recruitment
- Registry Or Advocacy Recruitment
- True, Epilepsy Study Consortium Inc.
- Digital Remote Recruitment
- True, includes eConsent (electronic consent) materials, eConsent videos/screenshots, online patient pre-screening website content and ePR website placeholders (country-specific eConsent and online recruitment materials referenced).
- Planned Sample Size
- 150
- Recruitment Window Months
- 30
- Consent Approach
- Informed consent obtained from patient and/or authorized representative; assent obtained from minors per age-appropriate assent forms. Study uses parental/legal guardian ICFs, assent forms (including assent over 12), additional caregiver ICFs, 'turning 18' materials for participants who reach adulthood during study, and eConsent materials. Documents available in multiple languages (English, French, Spanish, Italian, German, Polish and country-specific versions).
Methods
- K1_Recruitment arrangements / recruitment procedure (study-level recruitment procedure document) — outlines overall recruitment process and channels.
- Parent-caregiver brochure (K2) — patient-facing printed/online material targeted to parents and caregivers; country/language-specific versions available (e.g., ESP, ITA, FRA, SWE).
- Physician referral letter (K2) — targeted to clinicians to facilitate referrals.
- Website content / ePR / patient pre-screening website content — online recruitment and pre-screening channel (ePR website placeholders and patient pre-screening website documents listed).
- Lumbar puncture animation storyboard — educational multimedia to explain intrathecal procedure to participants/parents.
- eConsent materials and eConsent videos/screenshots — digital consent channel and supporting materials.
- Patient materials (study summaries, patient ID card, thank you cards) — patient-facing collateral to support recruitment and retention.
Geography
- Total Number Of Sites
- 30
- Total Number Of Participants
- 35
Sweden
- Earliest CTIS Part Ii Submission Date
- 28-07-2025
- Latest Decision Or Authorization Date
- 13-08-2025
- Processing Time Days
- 16
- Number Of Sites
- 3
- Number Of Participants
- 6
Sites
- Site Name
- Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
- Department Name
- Drottning Silvias barnsjukhus, Sahlgrenska Universitetssjukhuset
- Contact Person Name
- Tove Hallböök
- Contact Person Email
- tove.hallbook@vgregion.se
- Site Name
- Region Skane Skanes Universitetssjukhus
- Department Name
- Skånes Universitetssjukhus
- Contact Person Name
- Erik Eklund
- Contact Person Email
- erik.eklund@skane.se
- Site Name
- Karolinska University Hospital
- Department Name
- Karolinska Universitetssjukhuset
- Contact Person Name
- Ronny Wickström
- Contact Person Email
- ronny.wickstrom@ki.se
Poland
- Earliest CTIS Part Ii Submission Date
- 11-08-2025
- Latest Decision Or Authorization Date
- 08-09-2025
- Processing Time Days
- 28
- Number Of Sites
- 3
- Number Of Participants
- 9
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Department Name
- Oddział Kliniczny Neurologii Dzieci i Młodzieży
- Contact Person Name
- Barbara Steinborn
- Contact Person Email
- bstein@ump.edu.pl
- Site Name
- Instytut Centrum Zdrowia Matki Polki
- Department Name
- Klinika Neurologii Rozwojowej i Epileptologii
- Contact Person Name
- Łukasz Przysło
- Contact Person Email
- lukasz.przyslo@iczmp.edu.pl
- Site Name
- Uniwersyteckie Centrum Kliniczne
- Department Name
- Klinika Neurologii Rozwojowej
- Contact Person Name
- Maria Mazurkiewicz- Bełdzińska
- Contact Person Email
- mmazur@gumed.edu.pl
Spain
- Earliest CTIS Part Ii Submission Date
- 24-01-2025
- Latest Decision Or Authorization Date
- 30-06-2025
- Processing Time Days
- 157
- Number Of Sites
- 5
- Number Of Participants
- 3
Sites
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Neurology
- Contact Person Name
- Vicente Villanueva Haba
- Contact Person Email
- vevillanuevah@yahoo.es
- Site Name
- Hospital Ruber Internacional
- Department Name
- Neurology
- Contact Person Name
- Antonio Gil-Nagel Rein
- Contact Person Email
- agnagel@neurologiaclinica.es
- Site Name
- Hospital Blua Sanitas Valdebebas
- Department Name
- Neurology
- Contact Person Name
- Ángel Aledo Serrano
- Contact Person Email
- as.aledo@gmail.com
- Site Name
- Hospital De La Santa Creu I Sant Pau
- Department Name
- Neurology
- Contact Person Name
- Alba Sierra Marcos
- Contact Person Email
- asierram@santpau.cat
- Site Name
- Clinica Universidad De Navarra
- Department Name
- Paediatric Neurology
- Contact Person Name
- Rocío Sánchez-Carpintero Abad
- Contact Person Email
- rsanchezc@unav.es
Italy
- Earliest CTIS Part Ii Submission Date
- 06-08-2025
- Latest Decision Or Authorization Date
- 03-09-2025
- Processing Time Days
- 28
- Number Of Sites
- 5
- Number Of Participants
- 2
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Neurologia Infantile
- Contact Person Name
- Domenica Immacolata Battaglia
- Contact Person Email
- domenicaimmacolata.battaglia@policlinicogemelli.it
- Site Name
- IRCCS Istituto Giannina Gaslini
- Department Name
- Neurologia Pediatrica e Malattie Muscolari
- Contact Person Name
- Pasquale Striano
- Contact Person Email
- pasquale.striano@unige.it
- Site Name
- ASST Fatebenefratelli Sacco
- Department Name
- Neurologia Pediatrica
- Contact Person Name
- Silvia Masnada
- Contact Person Email
- silvia.masnada@asst-fbf-sacco.it
- Site Name
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Department Name
- Neuroscience and Human Genetics Department - Neurologia Peditrica
- Contact Person Name
- Renzo Guerrini
- Contact Person Email
- renzo.guerrini@meyer.it
- Site Name
- Ospedale Pediatrico Bambino Gesu
- Department Name
- Neurologia dell'Epilessia e Disturbi del movimento
- Contact Person Name
- Nicola Specchio
- Contact Person Email
- nicola.specchio@opbg.net
Germany
- Earliest CTIS Part Ii Submission Date
- 25-08-2025
- Latest Decision Or Authorization Date
- 08-09-2025
- Processing Time Days
- 14
- Number Of Sites
- 7
- Number Of Participants
- 12
Sites
- Site Name
- Universitaetsklinikum Bonn AöR
- Department Name
- Neuropädiatrie und Sozialpädiatrisches Zentrum
- Contact Person Name
- Walid Fazeli
- Contact Person Email
- studienzentrale-szb@ukbonn.de
- Site Name
- Medical Center - University Of Freiburg
- Department Name
- KJK Neuropaediatrie und Muskelerkrankungen
- Contact Person Name
- Jan Schönberger
- Contact Person Email
- jan.schoenberger@uniklinik-freiburg.de
- Site Name
- Gesellschaft Fuer Epilepsieforschung
- Department Name
- Department for Epileptology
- Contact Person Name
- Tilman Polster
- Contact Person Email
- tilman.polster@mara.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- paedKiiS
- Contact Person Name
- Steffen Syrbe
- Contact Person Email
- steffen.syrbe@med.uni-heidelberg.de
- Site Name
- Ludwig-Maximilians-Universitaet Muenchen
- Department Name
- Department of Pediatric Neurology, Developmental Medicine and Social Pediatrics
- Contact Person Name
- Ingo Borggraefe
- Contact Person Email
- ingo.borgraeffe@med.uni-muenchen.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik für Pädiatrie m.S. Neruologie
- Contact Person Name
- Angela Kaindl
- Contact Person Email
- angela.kaindl@charite.de
- Site Name
- Goethe University Frankfurt
- Department Name
- Klinik für Kindee und Jugendmedizin
- Contact Person Name
- Susanne Schubert-Bast
- Contact Person Email
- schubert-bast@med.uni-frankfurt.de
France
- Earliest CTIS Part Ii Submission Date
- 18-07-2025
- Latest Decision Or Authorization Date
- 28-07-2025
- Processing Time Days
- 10
- Number Of Sites
- 7
- Number Of Participants
- 3
Sites
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Service de Neurométabolisme Pédiatrique
- Contact Person Name
- Mathieu MILH
- Contact Person Email
- mathieu.milh@ap-hm.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Service Neurologie Pédiatrique
- Contact Person Name
- Anne DE SAINT-MARTIN
- Contact Person Email
- anne.desaintmartin@chru-strasbourg.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service Neurologie Pédiatrique
- Contact Person Name
- Rima EL NABBOUT - TARANTINO
- Contact Person Email
- rima.nabbout@aphp.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service Neurologie Pédiatrique
- Contact Person Name
- Stéphane AUVIN
- Contact Person Email
- stephane.auvin@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Service Epileptologie Clinique, Troubles du Sommeil, Neurologie Fonctionnelle de l’Enfant
- Contact Person Name
- Joseph TOULOUSE
- Contact Person Email
- joseph.toulouse@chu-lyon.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Service Neuropédatrie et Handicaps
- Contact Person Name
- Maximilien PERIVIER
- Contact Person Email
- m.perivier@chu-tours.fr
- Site Name
- Hospices Civils De Lyon (additional listing)
- Department Name
- Service Epileptologie Clinique, Troubles du Sommeil, Neurologie Fonctionnelle de l’Enfant
Sponsor
Primary sponsor
- Full Name
- Stoke Therapeutics Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- Operational/execution roles (sponsorDuties codes: 1,12,13,2,3,5,8) and EU clinical trials information contact (eu_clinical_trials_information@iqvia.com).
- Name
- PPD Development LP
- Responsibilities
- Sample analysis (PK, CSF bioA, ADA)
- Name
- PPD International Holdings LLC
- Responsibilities
- Site services (siteservices.eu@ppdi.com)
- Name
- Fisher Clinical Services GmbH / Fisher Clinical Services UK Limited
- Responsibilities
- Clinical packaging/ancillary kits and logistics (contacts provided)
Third parties
- {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
- {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"Rating Scales Mgmt, Vineland-3 Central Rating & Cognitive Assessments","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG Central Reader","organisation_type":"Pharmaceutical company"}
- {"country":"Finland","full_name":"Blueprint Genetics Oy","duties_or_roles":"Genetic testing","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Sample analysis (PK, CSF bioA, ADA)","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1, 12, 13, 2, 3, 5, 8","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Equipment","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"Icometrix","duties_or_roles":"MRI scan reading","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"Exploratory CSF and Serum Protein Characterization","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Red Nucleus Solutions LLC","duties_or_roles":"Caregiver assessment","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Non-Pharmaceutical company"}
- {"country":"France","full_name":"Cerba","duties_or_roles":"CSF Protein Total","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"Ancillary kits management","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"Biostats, DSMC (data and safety monitoring committee); codes 10, 6, 7","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Concierge Services and Patient payment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Epilepsy Study Consortium Inc.","duties_or_roles":"Diagnostic Review – Seizure ID and Diagnostic Review","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- STK-001
- Active Substance
- ZOREVUNERSEN SODIUM
- Modality
- Oligonucleotide
- Routes Of Administration
- INTRATHECAL USE
- Route
- Intrathecal
- Authorisation Status
- prodAuthStatus: 1
- Orphan Designation
- Yes
- Maximum Dose
- 225 mg (maxTotalDoseAmount)
- Investigational Product Name
- STK-001
- Active Substance
- ZOREVUNERSEN SODIUM
- Modality
- Oligonucleotide
- Routes Of Administration
- INTRATHECAL USE
- Route
- Intrathecal
- Authorisation Status
- prodAuthStatus: 1
- Orphan Designation
- Yes
- Maximum Dose
- 140 mg (maxTotalDoseAmount)
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