EMPEROR: A Double-blind Study Evaluating the Efficacy, Safety, and Tolerability of Zorevunersen (STK-001) in Patients with Dravet Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stoke Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Mar 2026 → ongoing

Decision date (initial)

2025-07-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Stoke Therapeutics Inc.

External identifiers

EU CT number

2024-519555-28-00

ClinicalTrials.gov

NCT06872125

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Others

To assess the effect of zorevunersen to reduce the frequency of major motor seizures in patients with DS. Major motor seizures are defined as the following seizure types: 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 objectives 3

1. To assess the durability of zorevunersen to reduce the frequency of major motor seizures in patients with DS
2. To assess the effect of zorevunersen on a multi-component measure of key comorbidities associated with DS
3. To assess the effect of zorevunersen on measures of key comorbidities associated with DS

Conditions and MedDRA coding

Dravet syndrome

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000022-PIP62-01

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Patient and their caregiver must be willing and able (in the Investigator’s opinion) to comply with all protocol requirements.
3. At signing of consent/assent, patient must be ≥2 and <18 years of age.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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 6

1. 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.
2. 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.
3. 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.
4. Patient is currently treated with neuromodulation techniques (e.g., responsive neurostimulation, deep brain stimulation, or transcranial magnetic stimulation), with the exception of VNS.
5. 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.
6. 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 and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 3

1. 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).
2. Net treatment benefit across multiple Vineland 3 outcomes, assessed as change from baseline, in patients receiving zorevunersen as compared with sham at Week 52.
3. Change from baseline in subdomain scores on the Vineland-3 in patients receiving zorevunersen as compared with sham at Week 52.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stoke Therapeutics Inc.

Sponsor organisation

Stoke Therapeutics Inc.

Address

45 Wiggins Avenue

City

Bedford

Postcode

01730-2314

Country

United States

Scientific contact point

Organisation

Stoke Therapeutics Inc.

Contact name

Ann Dandurand

Public contact point

Organisation

Stoke Therapeutics Inc.

Contact name

Ann Dandurand

Third parties 17

Locations

6 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 100 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications