UK approves first gene-specific trial to treat Dravet Syndrome
Today Stoke Therapeutics announced that they have received approval to start a clinical trial in the UK for a developmental treatment for Dravet Syndrome, currently known as STK-001.
If the clinical trial is successful, STK-001 could be the first gene-specific (to SCN1A), disease-modifying approach to treating Dravet Syndrome, with the aim of improving both seizures and comorbidities.
Known as ‘ADMIRAL’, the UK clinical trials will be open to a small number of children and young people with SCN1A-related Dravet Syndrome, aged 2-17 years. Professor Helen Cross, Chair of DSUK’s Medical Advisory Board, is confirmed as the study’s lead investigator.
This trial follow on from the first clinical trial of STK-001 (called the MONARCH Study), started in the US in June 2020 with children and young people with SCN1A-related Dravet Syndrome, and which is ongoing and expected to conclude late 2022.
While this is an exciting development, it is very much a first step, with recruitment still some months away. It is anticipated that 22 patients will be enrolled in this study, which is primarily designed to evaluate safety but will also evaluate potential clinical benefit as measured by change in seizure frequency.
We know this study will be of considerable interest to the Dravet Syndrome community and we will be sure to keep you updated with all the latest developments as and when they become available.
What is STK-001?
STK-001 has been developed specifically to treat SCN1A-related Dravet Syndrome where someone has one healthy copy of a gene and one mutated copy. If there's only one functional copy of SCN1A then it may produce too little protein for the brain to work as it should, causing seizures, intellectual disabilities and a range of other conditions. STK-001 works by helping the functional gene to increase protein production, with the aim of restoring protein levels to near normal levels, and hopefully in doing so addressing the underlying causes of Dravet Syndrome.
More information can be found in our Q&A here.
What do we know so far?
STK-001 significantly decreased seizure frequency and increased survival in a mouse model of Dravet Syndrome. STK-001 has also been tested in healthy non-human primates and shown to increase the Nav1.1 sodium channel without any adverse effects on the animals. These pre-clinical results are encouraging, but it is yet to be seen how this will work in human patients with Dravet Syndrome. More information can be found here.
What do we know about the UK study?
The ADMIRAL study is a Phase 1/2a open-label study of children and young people aged 2 to up to 18 who have a diagnosis of Dravet Syndrome and evidence of a genetic mutation in the SCN1A gene.
The primary objectives for the study are to assess the safety and tolerability of multiple doses of STK-001, as well as to characterise human pharmacokinetics. A secondary objective is to assess the effect of multiple doses of STK-001 as an adjunctive anti-seizure treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 24-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints.
Stoke plans to enrol approximately 22 patients in the study across multiple sites in the UK. More information can be found here.