The purpose of the study is to evaluate the efficacy, safety, and tolerability of zorevunersen in Patients with Dravet syndrome.
Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. It is an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1 protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does not manipulate nor insert genetic deoxyribonucleic acid (DNA). Zorevunersen is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type) copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in people with Dravet syndrome. This is a global, multicenter, randomized, double-blind, sham-controlled, parallel group Phase 3 study to assess the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome. The study duration and endpoints are designed to evaluate the potential of zorevunersen for disease modification. The study consists of two parts, Treatment Period 1 and Treatment Period 2. The primary and secondary endpoints will be assessed at the conclusion of Treatment Period 1. These endpoints will be assessed again at the end of Treatment Period 2. The primary endpoint is the change from baseline in major motor seizure frequency. Secondary endpoints include the change in behavior and cognition, clinical status, and health-related quality of life in patients with Dravet syndrome. Patients will have the opportunity to enroll in an open label extension study and receive zorevunersen if they meet eligibility criteria at the end of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
170
Treatment Period 1: Zorevunersen group will receive study drug by intrathecal (IT) administration on Day 1 (after the 8-week Baseline Period), Day 57 (Week 8), Day 169 (Week 24), and Day 281 (Week 40) at a dose level of 70 mg on Day 1 and Day 57, and 45 mg on Day 169 and Day 281. Treatment Period 2: Group assigned to zorevunersen in Treatment Period 1 will receive 45 mg of zorevunersen on Day 393 (Week 56), Day 477 (Week 68), and Day 589 (Week 84).
Treatment Period 1: Sham group will not have drug administered. Sham group will have a procedure intended to mimic the drug administration. Treatment Period 2: Group assigned to sham in Treatment Period 1 will receive 70 mg of zorevunersen on Day 393 (Week 56) and on Day 477 (Week 68), and 45 mg of zorevunersen Day 589 (Week 84).
Measurement of Seizure Change
Measured by daily seizure diary
Time frame: Week 28
Measurement of Seizure Change
Measured by daily seizure diary
Time frame: Week 52
Multi-component Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Outcome Score
Measurement of change from baseline for multi-component score. Scoring is non-parametric and based on rank between treatment and sham groups. Individual items are scored on a scale of 0, 1, or 2, indicating never, sometimes, or usually or often, or on a scale of 0 or 2, indicating no or yes, with higher scores indicating greater performance
Time frame: Week 52
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Subdomain Score
Measurement of change from baseline for individual subdomains. Scoring is point-based on a scale that varies, depending on subdomain, Individual items are scored on a scale of 0, 1, or 2, indicating never, sometimes, or usually or often, or on a scale of 0 or 2, indicating no or yes, with higher scores indicating greater performance.
Time frame: Week 52
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