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
Abstract number :
1.216
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2022
Submission ID :
2204349
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Colin Roberts, MD – OHSU; Scott Perry, MD – Cook Children's Hospital; Joseph Sullivan, MD – UCSF; Matt Lallas, MD – NeuroNetwork Partners; Orrin Devinsky, MD – NYU; Kelly Knupp, MD – Children's Hospital Colorado; Linda Laux, MD – Ann & Robert H. Lurie Children's Hospital of Chicago; John Schreiber, MD – Children's National Hospital; Charlene Brathwaite, NA – Stoke Therapeutics; Javier Avendaño, MD – Stoke Therapeutics; James Stutely, NA – Stoke Therapeutics; Nancy Wyant, NA – Stoke Therapeutics; Meena M, PhD – Stoke Therapeutics; Kimberly Parkerson, MD – Stoke Therapeutics; Barry Ticho, MD – Stoke Therapeutics
Rationale: DS is a severe and progressive genetic developmental and epileptic encephalopathy that typically begins in the first year of life. Approximately 85% of cases are caused by heterozygous, loss of function, de novo mutations in the SCN1A gene, which encodes the voltage-gated sodium channel type 1 α subunit (Nav1.1) protein. DS is characterized by high seizure frequency (SF) and severity, intellectual disability, motor abnormalities, and a high risk of sudden unexplained death in epilepsy. STK-001 is an investigational ASO treatment designed to upregulate Nav1.1 protein expression in the brain by leveraging the wild-type (non-mutant) copy of SCN1A to restore physiological Nav1.1 levels, thereby potentially reducing both SF and non-seizure comorbidities.
Methods: SWALLOWTAIL (NCT04740476) is an ongoing multi-center OLE study in the U.S., assessing the long-term safety, tolerability, plasma and CSF exposure and clinical effect of repeat doses of STK-001 administered every 4 months by intrathecal (IT) injection in patients with DS who have completed MONARCH (NCT04442295), a Phase 1/2a study of STK-001. Upon study entry, patients received, or will receive, the same dose level (10, 20, 30, or 45 mg) they received in MONARCH, or a dose level recommended by the safety monitoring committee. Adverse events (AEs) are monitored continuously, and CSF and plasma samples are collected at each visit. Clinical assessments including SF, neurodevelopmental status, gait, and executive functioning are evaluated during the study.
Results: As of 21Feb22, 19 of 20 patients (95%) who completed MONARCH (at the 10, 20, or 30 mg dose levels) enrolled in SWALLOWTAIL. Demographics and AEs are shown in the table; patients are summarized according to entering dose level. Additional available safety, clinical assessments, plasma and CSF exposure data will be reported.
Conclusions: Data to date indicate that IT doses of STK-001 up to 30 mg administered every 4 months are well-tolerated with no safety concerns related to study drug. 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.
Funding: Stoke Therapeutics
Clinical Epilepsy