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- | Journal, Metastases: Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development. (Pubmed Central) - Aug 22, 2024
For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.
- ||| STK-001 / Stoke Therap
Trial completion, Trial completion date, Trial primary completion date: An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome (clinicaltrials.gov) - Apr 22, 2024
P1/2, N=62, Completed, Sponsor: Stoke Therapeutics, Inc
For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date. Active, not recruiting --> Completed | Trial completion date: May 2025 --> Apr 2024 | Trial primary completion date: Sep 2024 --> Dec 2023
- || Review, Journal: New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. (Pubmed Central) - Aug 21, 2023
The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.
- || STK-001 / Stoke Therap
Enrollment closed: An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome (clinicaltrials.gov) - Jun 27, 2023
P1/2, N=78, Active, not recruiting, Sponsor: Stoke Therapeutics, Inc
To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management. Recruiting --> Active, not recruiting
- STK-001 / Stoke Therap
SWALLOWTAIL: An Open-Label Extension (OLE) Study for Children and Adolescents with Dravet Syndrome (DS) who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001 (Foyer 3B, 3rd Floor) - May 29, 2023 - Abstract #EPNS2023EPNS_515;
P1/2, P2
These data support continued development of STK-001 as the first potential disease-modifying approach to treat DS. This study will inform on the long-term safety and tolerability of repeat administration of STK-001 and will help inform future clinical studies of STK-001.
- STK-001 / Stoke Therap
MONARCH and ADMIRAL Interim Analyses: Phase 1/2a Studies Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) (Congress Hall, 2nd Floor) - May 29, 2023 - Abstract #EPNS2023EPNS_184;
P1/2
These data support continued development of STK-001 as the first potential disease-modifying approach to treat DS. Together with the OLEs, these data will help inform future clinical studies of STK-001.
- STK-001 / Stoke Therap
ADMIRAL: A Phase 1/2a UK Study Investigating the Safety and Pharmacokinetics (PK) of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) (Hall B, Level 3) - Nov 29, 2022 - Abstract #AES2022AES_1402;
P1/2
Data to date indicate that multiple doses of 30mg of STK-001 are well-tolerated with no safety concerns related to study drug and support continued development of STK-001 as the first potential disease-modifying approach to treat DS. Together with the US MONARCH (NCT04442295) study, these data will help inform future clinical studies of STK-001.
- STK-001 / Stoke Therap
MONARCH Interim Analyses: A Phase 1/2a US Study Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) (Hall B, Level 3) - Nov 29, 2022 - Abstract #AES2022AES_1351;
P1/2, P2
Dose-dependent increases in plasma exposure have been observed. STK-001 was detected in CSF samples up to 6 months post single dose at all dose levels indicating sustained STK-001 exposure in brain.
- STK-001 / Stoke Therap
SWALLOWTAIL: An Open-label Extension (OLE) Study for Children and Adolescents with Dravet Syndrome (DS) Who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001 (Hall B, Level 3) - Nov 29, 2022 - Abstract #AES2022AES_1331;
P1/2, P2
These data support continued development of STK-001 as the first potential disease-modifying approach to treat DS. This study will inform on the long-term safety and tolerability of repeat administration of STK-001, and together with the U.S. MONARCH and U.K. ADMIRAL studies, these data will help inform future clinical studies of STK-001.
- STK-001 / Stoke Therap
Utilization of a Pharmacokinetic (PK) Model for STK-001 in Patients with Dravet Syndrome (DS) to Predict Pharmacological Active Dose in Clinic (Hall B, Level 3) - Nov 29, 2022 - Abstract #AES2022AES_1327;
The PK model developed with NHP data along with published data for animal to human scaling was leveraged to predict the pharmacologically active doses of STK-001 in pediatric patients with DS. The model will be further validated or adjusted using data from ongoing non-clinical studies and phase 1/2 and open-label extension studies in patients with DS receiving STK-001.
- STK-001 / Stoke Therap
Quantitative EEG Analysis in Patients with Dravet Syndrome (DS) Treated in the Phase 1/2a MONARCH Study of STK-001, an Antisense Oligonucleotide (ASO) () - Nov 29, 2022 - Abstract #AES2022AES_816;
P1/2
Greater theta compared with alpha power in younger and older age groups is consistent with prior data showing increased theta and decreased alpha in children with DS after 6 years compared with controls (Holmes et al 2012). Initial trends indicate modulation of theta and alpha power may be a useful tool following treatment with STK-001.Reference:Holmes et al.
- STK-001 / Stoke Therap
STK-001 Surrogate Restores the Excitability of Parvalbumin-positive Fast-spiking Interneurons in a Mouse Model of Dravet Syndrome () - Nov 29, 2022 - Abstract #AES2022AES_770;
Initial trends indicate modulation of theta and alpha power may be a useful tool following treatment with STK-001.Reference:Holmes et al. STK-001 surrogate ASO treatment restores Scn1a+/- DS PV+ interneuron excitability and GABA release in a DS mouse model.
- || Review, Journal: Dravet syndrome: Advances in etiology, clinical presentation, and treatment. (Pubmed Central) - Nov 15, 2022
Later therapeutic options include other anti-seizure medications, the ketogenic diet, and vagus nerve stimulation, whereas sodium channel blockers should be avoided in DS. Furthermore, several promising drugs including soticlestat are in development, and genetic therapies are beginning to emerge, representing future treatment directions.
- | Journal: Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development. (Pubmed Central) - Nov 15, 2022
These compounds include bumetanide and its derivatives, darigabat, ganaxolone, lorcaserin, soticlestat, STK-001, and XEN1101. Of these, ganaxolone was approved by the US Food and Drug Administration in March 2022 for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder in patients 2 years of age and older.
- ||| Ztalmy (ganaxolone oral) / Marinus
P2/3 data, Clinical Trial,Phase III, Journal: Epilepsy: Expert opinion on emerging drugs in phase 2/3 clinical trials. (Pubmed Central) - Apr 6, 2022
Novel mechanisms of action involve cholesterol degradation, mitochondrial pathways, anti-inflammation and neuro-regeneration. Earlier identification of genetic conditions through genetic testing will allow for earlier use of disease specific and disease-modifying therapies.
- | STK-001 / Stoke Therap
Preclinical, Journal: Targeted Augmentation of Nuclear Gene Output (TANGO) of SCN1A Rescues Parvalbumin Interneuron Excitability and Reduces Seizures in a Mouse Model of Dravet Syndrome. (Pubmed Central) - Mar 26, 2022
In this study, we demonstrate that STK-001 treatment reduces seizures, prolongs survival, and rescues PV interneuron excitability in Scn1a mice to levels observed in WT littermates. Together, these results support the notion that TANGO-mediated augmentation of Na1.1 levels directly targets and rescues one of the core disease mechanisms of DS.
- || STK-001 / Stoke Therap
Trial completion date, Trial primary completion date: An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome (clinicaltrials.gov) - Mar 4, 2022
P1/2, N=78, Recruiting, Sponsor: Stoke Therapeutics, Inc
Together, these results support the notion that TANGO-mediated augmentation of Na1.1 levels directly targets and rescues one of the core disease mechanisms of DS. Trial completion date: Mar 2024 --> May 2025 | Trial primary completion date: Jun 2023 --> Sep 2024
- ||| STK-001 / Stoke Therap
Enrollment change, Trial completion date, Trial primary completion date: An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome (clinicaltrials.gov) - Mar 4, 2022
P2, N=69, Enrolling by invitation, Sponsor: Stoke Therapeutics, Inc
Trial completion date: Mar 2024 --> May 2025 | Trial primary completion date: Jun 2023 --> Sep 2024 N=48 --> 69 | Trial completion date: Sep 2024 --> Mar 2027 | Trial primary completion date: Sep 2024 --> Feb 2026
- || Spinraza (nusinersen) / Biogen, Ionis, STK-001 / Stoke Therap
Review, Journal: Antisense Oligonucleotide Therapy for Neurodevelopmental Disorders. (Pubmed Central) - Jan 28, 2022
An ASO that reduces the abundance of the SCN8A mRNA is therapeutic in mouse models of developmental and epileptic encephalopathy. These examples demonstrate the variety of mechanisms and range of applications of ASOs for treatment of neurodevelopmental disorders.
- STK-001 / Stoke Therap
Positive Interim Safety, PK, and CSF Exposure Data from the Phase 1/2a MONARCH Study of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) () - Dec 12, 2021 - Abstract #AES2021AES_1453;
P1/2
There was a trend toward reduced convulsive seizure frequency. These data support continued development of STK-001 as the first disease-modifying precision medicine for DS.
- STK-001 / Stoke Therap
SWALLOWTAIL: An Open-Label Extension (OLE) Study for Patients with Dravet Syndrome (DS) Who Previously Participated in Studies of STK-001 () - Dec 12, 2021 - Abstract #AES2021AES_1384;
P1/2, P2
STK-001 has the potential to be the first-in-class, disease-modifying therapy to address the genetic cause of DS by upregulating Nav1.1 protein levels to reduce seizures and decrease the likelihood of DS non-seizure comorbidities. The results will inform on the long-term safety of repeat administration of STK-001 and will help determine appropriate and effective STK-001 dosing in future clinical studies.
- STK-001 / Stoke Therap
ADMIRAL: An UK, Open-Label Study to Investigate the Safety and Pharmacokinetics of Multiple Ascending Doses of Antisense Oligonucleotide (ASO) STK-001 in Children and Adolescents with Dravet Syndrome () - Dec 12, 2021 - Abstract #AES2021AES_1227;
STK-001 has the potential to be the first-in-class, disease-modifying therapy to address the genetic cause of DS by upregulating Nav1.1 protein levels and to potentially reduce both occurrence of seizures and non-seizure comorbidities. Together with the US MONARCH study, the ADMIRAL data may better inform future clinical trials on appropriate and effective STK-001 dosing.
- STK-001 / Stoke Therap
A Pharmacokinetic (PK) Model for STK-001, an Antisense Oligonucleotide (ASO), Based on Data from Non-human Primates (NHP) Enables Dose Selection in Patients with Dravet Syndrome (DS) () - Dec 12, 2021 - Abstract #AES2021AES_964;
The PK model developed with NHP data along with published data for animal-human scaling was leveraged to support dosing recommendations in pediatric patients with DS. The model simulations will be further validated with data from an ongoing phase 1/2a clinical trial in patients with DS receiving STK-001.
- | clemizole (EPX-100) / Epygenix Therap
Journal: Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome. (Pubmed Central) - Oct 16, 2021
Experimental data and results from initial clinical studies have brought attention to several drugs with various mechanisms of action including: ataluren (a suppressant of premature stop codons; under clinical evaluation), EPX-100, EPX-200, fenfluramine (serotonin modulators), soticlestat (an 24-hydroxylase cholesterol enzyme inhibitor), SPN-817 (an inhibitor of acetylcholinesterase), verapamil (a voltage-dependent calcium channel inhibitor) and STK-001 (an antisense oligonucleotide). The latter is scheduled for clinical evaluation.
- ||| STK-001 / Stoke Therap
Enrollment change, Trial completion date, Trial primary completion date: An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome (clinicaltrials.gov) - Feb 22, 2021
P1/2, N=70, Recruiting, Sponsor: Stoke Therapeutics, Inc
The latter is scheduled for clinical evaluation. N=48 --> 70 | Trial completion date: Oct 2022 --> Mar 2024 | Trial primary completion date: Sep 2021 --> Jun 2023
- || STK-001 / Stoke Therap
New P2 trial: An Open-Label Extension Study of STK-001 for Patients With Dravet Syndrome (clinicaltrials.gov) - Feb 4, 2021
P2, N=48, Enrolling by invitation, Sponsor: Stoke Therapeutics, Inc
- STK-001 / Stoke Therap
[VIRTUAL] Safety and Pharmacokinetics of Antisense Oligonucleotide STK-001 in Children and Adolescents with Dravet Syndrome: Single Ascending Dose Design for the Open-Label Phase 1/2a MONARCH Study () - Nov 28, 2020 - Abstract #AES2020AES_1217;
The dose implications of this study may better inform future clinical trials on the appropriate and effective dosing for efficacy measures. Funding: Sponsored by Stoke Therapeutics
- STK-001 / Stoke Therap
[VIRTUAL] Targeted Augmentation of Nuclear Gene Output (TANGO) of SCN1A Reduces Seizures and Rescues Parvalbumin Positive Interneuron Firing Frequency in a Mouse Model of Dravet Syndrome () - Nov 28, 2020 - Abstract #AES2020AES_782;
Further, the current data support the hypothesis that the improvement in DS phenotype is in part due to restoration of excitability of PV expressing interneurons. Funding: Sponsored by Stoke Therapeutics
- | STK-001 / Stoke Therap
New P1/2 trial: An Open-Label Study to Investigate the Safety of Single and Multiple Ascending Doses in Children and Adolescents With Dravet Syndrome (clinicaltrials.gov) - Jun 22, 2020
P1/2, N=48, Recruiting, Sponsor: Stoke Therapeutics, Inc