SWALLOWTAIL: An Open-Label Extension (OLE) Study for Patients with Dravet Syndrome (DS) Who Previously Participated in Studies of STK-001
Abstract number :
2.22
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1826106
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Colin Roberts, MD - OHSU; Scott Perry - Cook Children's; Steven Phillips - MultiCare Tacoma General Hospital; Joseph Sullivan - UCSF; Matt Lallas - NeuroNetwork Partners; Linda Laux - Northwestern Feinberg School; Ann & Robert H. Lurie Children’s Hospital; John Schreiber - Children's National Hospital; Carrie Condon - Stoke Therapeutics; Javier Avendaño - Stoke Therapeutics; Kimberly Parkerson - Stoke Therapeutics; Nancy Wyant - Stoke Therapeutics; Barry Ticho - Stoke Therapeutics
Rationale: DS is a severe and progressive genetic epilepsy that typically begins in the first year of life and is characterized by frequent, prolonged, and refractory seizures. Non-seizure comorbidities include intellectual disability, ataxia/motor abnormalities, behavioral problems, speech impairment, sleep disturbances, and a high risk for sudden unexpected death. Approximately 85% of DS cases are caused by de novo, spontaneous, heterozygous loss of function mutations in the SCN1A gene which encodes the voltage-gated sodium channel type 1α subunit (Nav1.1) protein. STK-001 is an investigational antisense oligonucleotide (ASO) treatment designed to upregulate Nav1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological Nav1.1 levels, thereby reducing both occurrence of seizures and substantial non-seizure comorbidities.
Methods: SWALLOWTAIL (NCT04740476) is a 15-month, multi-center, open-label extension study of multiple doses of STK-001 for patients with DS (ages 2.5 to 19 years old) who have completed MONARCH (NCT04442295), a STK-001 Phase 1/2a study. Patients will be administered the same dose (10, 20, or 30mg) level they received in MONARCH. SWALLOWTAIL primarily aims to gather additional information on the long-term safety and tolerability of 3 doses of STK-001 administered 4 months apart by intrathecal (IT) injection, with a 6-month follow-up after the last dose. Adverse events (AEs) are monitored continuously, and plasma is collected for pharmacokinetics (PK) at each clinic visit. Seizure frequency, overall clinical status, and quality of life, as well as neurodevelopmental status, are evaluated during the study.
Results: As of 06APR2021, 3 patients have enrolled in the SWALLOWTAIL study following completion of the 10mg single administration dosing (SAD) cohort in the MONARCH study. One patient has experienced 2 treatment-emergent adverse events (TEAEs), and both were graded as mild. Neither TEAE was related to STK-001. One TEAE was related to IT administration. There have not been any SAEs recorded to date. Additional safety and PK data will be reported.
Conclusions: 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.
Funding: Please list any funding that was received in support of this abstract.: Stoke Therapeutics.
Anti-seizure Medications