Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT06112275
Ethics application status
Date submitted
25/10/2023
Date registered
1/11/2023
Date last updated
21/08/2024

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 evaluate ETX101 dose level 1.

Experimental: Cohort Y - Cohort Y will evaluate ETX101 dose level 2.

Experimental: Cohort Z - Cohort Z will evaluate ETX101 dose level 3.


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-Third Edition Expressive Communication raw score at Week 52.
Timepoint [2] 0 0
Baseline through Week 52. 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 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
6 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
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
Actual
28/02/2024
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 6 to \<84 months. The study follows an open-label, dose-escalation design.
Trial website
https://clinicaltrials.gov/study/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
[email protected]
Contact person for scientific queries



Summary Results

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