A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-935 (OV935) as an Adjunctive Therapy in Pediatric Participants With Developmental and/or Epileptic Encephalopathies
- Conditions
- Dravet SyndromeLennox-Gastaut SyndromeEpilepsy
- Interventions
- Drug: PlaceboDrug: TAK-935
- Registration Number
- NCT03650452
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this study is to investigate the effect on the frequency of all seizures (convulsive and drop) in participants treated with TAK-935 compared to placebo.
- Detailed Description
The drug being tested in this study is called TAK-935 (OV935). This randomized, double-blind study will assess the effects of TAK-935 (OV935), compared to placebo, on efficacy, safety, and tolerability in pediatric participants with Dravet syndrome (DS) or Lennox Gastaut syndrome (LGS). This multi-center trial will be conducted worldwide and will enroll approximately 126 participants.
Participants will be randomized based on their diagnosis in 2 categories; DS or LGS. The study will consist of 2 periods: Screening Period and Treatment Period. The overall duration of Treatment Period is up to 20 weeks including 8-week Dose Optimization Period and 12-week Maintenance Period. The overall time to participants in this study is approximately 30 weeks.
Participants completing this study will have an option to enroll in the open-label extension study, under a separate protocol.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
- Male and female participants aged greater than or equal to (>=) 2 and less than or equal to (<=) 17 years
- Clinical diagnosis of DS or LGS
- Weight of >=10 kilogram (kg) at the Screening visit
- Currently taking 1 to 4 anti-epileptic drugs (AEDs) at a stable dose
- Failed to become and remain seizure free with trials of at least 2 AEDs
- Has been admitted to a medical facility and intubated for treatment of status epilepticus 2 or more times in the 3 months immediately prior to the screening visit
- Non-epileptic events that cannot be reliably distinguished from epileptic seizures
- Participation in a clinical study involving another study drug in the previous month
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo TAK-935 placebo-matching tablets, orally or via gastrostomy tube (G-tube)/percutaneous endoscopic gastrostomy (PEG), twice a day (BID) up to Week 20. TAK-935 TAK-935 TAK-935 tablets orally or via G-tube/PEG tube, BID. Participants weighing \<60 kg received total daily dose of study drug calculated based on body weight. Participants weighing ≥60 kg at Baseline, were administered with 200 mg/day followed by 400 mg/day, then 600 mg/day, up to Week 20.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period Baseline; Maintenance Period: Weeks 9 to 20 Seizure frequency per 28 days is defined as total number of seizures (convulsive seizures for DS, drop seizures for LGS) reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent change from Baseline is defined as (frequency of seizures per 28 days during maintenance period - frequency of seizures per 28 days at baseline) divided by frequency of seizures per 28 days at baseline multiplied by 100. Negative percent change from Baseline indicates improvement.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period Baseline; Maintenance Period: Weeks 9 to 20 Drop seizure frequency per 28 days is defined as total number of drop seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement.
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period Baseline; Treatment Period: Weeks 0 to 20 Seizure Frequency per 28 days is defined as total number of Seizures reported (convulsive seizures for DS, drop seizures for LGS) during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline is defined as (frequency of seizures per 28 days during treatment period - frequency of seizures per 28 days at baseline) divided by frequency of seizures per 28 days at baseline multiplied by 100. Negative percent change from Baseline indicates improvement.
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period Baseline; Maintenance Period: Weeks 9 to 20 Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed multiplied by 28. Percent Change from Baseline (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Negative percent change from Baseline indicates improvement.
Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period Maintenance Period: Weeks 9 to 20 Responders are defined as having over 50% drop seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Drop Seizure Frequency - Baseline Period Drop Seizure Frequency) divided by Baseline Drop Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline.
Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period Maintenance Period: Weeks 9 to 20 Responders are defined as having over 50% convulsive seizure reduction compared to Baseline. Percent Reduction from Baseline (%) is defined as \[(Maintenance Period Convulsive Seizure Frequency - Baseline Period Convulsive Seizure Frequency) divided by Baseline Convulsive Seizure Frequency\] multiplied by 100. Data is reported as reduction of 25%, 50%, 75% and 100% or more in drop seizures from Baseline.
Change From Baseline in Clinician's Clinical Global Impression of Severity (CGI-S) Responses of Investigator Reported Impression of Efficacy and Tolerability of Study Drug Baseline and Week 20 The CGI-Severity (CGI-S) focuses on clinicians' observations of the participant's cognitive, functional, and behavioral performance since the beginning of the study. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill participants). A negative change from Baseline indicates improvement.
Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 Week 20 CGI-Change (CGI-C) treatment response ratings should take account of both therapeutic efficacy and treatment-related AEs. Each component of the CGI is rated separately; the instrument does not yield a global score. The CGI-C is rated on a 7-point scale, where, 0 = Marked improvement and no side-effects, 1 = Marked improvement and minimal side-effects, 2 = No Change, 3 = Minimal improvement and marked side-effects and 4 = Unchanged or worse and side-effects outweigh the therapeutic effect. Lower scores indicated improvement.
Percentage of Participants With Caregiver Global Impression of Change (Care GI-C) Responses as Per the Parent/Family Reported Impression of Efficacy and Tolerability of TAK-935 Week 20 The Care GI-C is rated on a 7-point scale, with the severity of illness scale where, 1 = Very much improved, 2 = Much improved, 3 = Slightly improved, 4 = No change, 5 = Slightly worse, 6 = Much worse and 7 = Very much worse. Lower scores indicated improvement.
Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy Baseline and Week 20 Seizure frequency was based on convulsive seizures for the participants in the Dravet Syndrome Indication and Drop Seizures for the participants in the LGS Indication. Seizure frequency per 28 days = (total number of seizures reported during the period) / (number of days during the period seizures were assessed) \* 28. A negative change from Baseline indicates improvement.
Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy Baseline and Week 24 A negative change from Baseline indicates improvement.
Trial Locations
- Locations (44)
Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Wielkopolskie, Poland
Schneider Childrens Medical Center of Israel
🇮🇱Petach Tikva, Israel
Rare Disease Research, LLC
🇺🇸Atlanta, Georgia, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Peking University First Hospital
🇨🇳Beijing, China
Columbia University Medical Center
🇺🇸New York, New York, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Colorado Children's Hospital
🇺🇸Aurora, Colorado, United States
Ann and Robert H Lurie Childrens Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Monash Children's Hospital
🇦🇺Clayton, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg West, Victoria, Australia
Hospital For Sick Children
🇨🇦Toronto, Ontario, Canada
Beijing Children's Hospital,Capital Medical University
🇨🇳Beijing, China
Capital Medical University (CMU) - Beijing Children's Hospital
🇨🇳Beijing, China
Xiangya Hospital Central South University
🇨🇳Changsha, China
Children's Hospital of Fudan University
🇨🇳Shanghai, China
Shenzhen Children's Hospital
🇨🇳Shenzhen, China
Sheba Medical Center-PPDS
🇮🇱Tel Hashomer,, Ramat Gan, Israel
Edith Wolfson Medical Center
🇮🇱Holon, Israel
Soroka University Medical Centre
🇮🇱Bear Sheva, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Uniwersyteckie Centrum Kliniczne - PPDS
🇵🇱Gdansk, Pomorskie, Poland
Clinica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
Centro Hospitalar Lisboa Central- Hospital Dona Estefania
🇵🇹Lisboa, Portugal
Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Hospital Vithas La Salud
🇪🇸Granada, Spain
Center for Rare Neurological Diseases
🇺🇸Norcross, Georgia, United States
Northeast Regional Epilepsy Group
🇺🇸Hackensack, New Jersey, United States
Pediatric Neurology PA
🇺🇸Orlando, Florida, United States
Mayo Clinic - PPDS
🇺🇸Rochester, Minnesota, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Children's Hospital at Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Hospital Ruber Internacional
🇪🇸Madrid, Spain
NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
🇵🇱Kielce, Swietokrzyskie, Poland
Instytut Pomnik Centrum Zdrowia Dziecka
🇵🇱Warsaw, Poland
Largo da Maternidade de Julio DinisCentro Materno Infantil do Norte
🇵🇹Porto, Portugal
Centrum Medyczne Plejady
🇵🇱Krakow, Poland
Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
🇵🇱Warsaw, Poland