Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06112275




Registration number
NCT06112275
Ethics application status
Date submitted
25/10/2023
Date registered
1/11/2023
Date last updated
15/02/2024

Titles & IDs
Public title
A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome (Australia Only)
Scientific title
WAYFINDER: A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
Secondary ID [1] 0 0
ETX-DS-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dravet Syndrome 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ETX101

Experimental: Cohort X - Cohort X will consist of 2 participants and will evaluate ETX101 dose level 1.

Experimental: Cohort Y - Cohort Y will consist of 2 participants and will evaluate ETX101 dose level 2.


Treatment: Drugs: ETX101
ETX101 is composed of a non-replicating, recombinant adeno-associated viral serotype 9 (rAAV9) vector used to deliver a GABAergic regulatory element (reGABA) and an engineered transcription factor that increases transcription of the SCN1A gene (eTFSCN1A).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of participants experiencing any treatment-emergent adverse events (AEs), serious adverse events (SAEs), related AEs, AEs with severity Grade = 3, AEs resulting in study discontinuation, and AEs with a fatal outcome.
Timepoint [1] 0 0
Day 1 through Study Completion, an average of 5 years
Primary outcome [2] 0 0
Percent change from Baseline in monthly countable seizure frequency (MCSF) at Week 52, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic bilateral, and atonic seizures.
Timepoint [2] 0 0
Between the 8-week baseline period and the 48-week post-dosing assessment period (defined as Week 5 to Week 52 following administration of ETX101)
Primary outcome [3] 0 0
Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.
Timepoint [3] 0 0
Week 5 through Week 52
Secondary outcome [1] 0 0
Proportion of participants with = 90% reduction in monthly countable seizure frequency (MCSF) from Baseline at Week 52.
Timepoint [1] 0 0
Between the 8-week baseline period and the 48-week post-dosing assessment period (defined as Week 5 to Week 52 following administration of ETX101)
Secondary outcome [2] 0 0
Change from Baseline in the Vineland Adaptive Behavior Scales - Third Edition score at Week 52.
Timepoint [2] 0 0
Baseline through Week 52. Standard scores are normalized to a mean and SD of 100 and 15, respectively, and are not bounded by a range. Higher scores correspond to better outcomes.

Eligibility
Key inclusion criteria
- Participant must have a predicted loss of function pathogenic or likely pathogenic
SCN1A variant.

- Participant must have experienced their first convulsive seizure between the ages of 3
and 15 months.

- Participant must have a clinical diagnosis of Dravet syndrome or the treating
clinician must have a high clinical suspicion of a diagnosis of Dravet syndrome.

- Participant is receiving at least one prophylactic antiseizure medication.
Minimum age
36 Months
Maximum age
83 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participant has another genetic mutation or clinical comorbidity which could
potentially confound the typical Dravet phenotype.

- Participant has a known central nervous system structural and/or vascular abnormality
(indicated by an MRI or CT scan of the brain).

- Participant has an abnormality that may interfere with CSF distribution and/or has an
existing ventriculoperitoneal shunt.

- Participant is currently taking or has taken antiseizure medications (ASMs) at a
therapeutic dose that are contraindicated in Dravet syndrome, including sodium channel
blockers.

- Participant has experienced seizure freedom for a period of 4 consecutive weeks within
the 6-month period prior to informed consent.

- Participant has previously received gene or cell therapy.

- Participant is currently enrolled in a clinical trial or receiving an investigational
therapy.

- Participant has clinically significant underlying liver disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/03/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2029
Actual
Sample size
Target
4
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Encoded Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
WAYFINDER is a Phase 1/2 study in Australia to evaluate the safety and efficacy of ETX101 in
participants with SCN1A-positive Dravet syndrome aged 36 to <84 months (3 to <7 years). The
study follows an open-label, dose-escalation design.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06112275
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Salvador Rico, M.D., Ph.D
Address 0 0
Encoded Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Encoded Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
+1 (650) 398-4301
Fax 0 0
Email 0 0
patientadvocacy@encoded.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06112275