Clinical trial NCT03650452: 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
Official title: 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 Patients With Developmental and/or Epileptic Encephalopathies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy
Dravet Syndrome
Lennox-Gastaut Syndrome
Keywords: Drug Therapy
Brain Diseases
Central Nervous System Diseases
Tuberous Sclerosis
CDKL5 deficiency disorder
Dup15Q syndrome
Anoxic brain injury
Infantile spams
West syndrome
Cortical dysplasia
SCN1A
OV-935
Cholesterol 24S-hydroxylase inhibitor
Seizure
Anti-epileptic drug
Anticonvulsants
Nervous System Diseases
Drop seizure
Atonic seizure
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Ovid Therapeutics Inc.
First posted: 2018-08-28
Enrollment: 141
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants aged greater than or equal to (\>=) 2 and less than or equal to (\<=) 17 years
2. Clinical diagnosis of DS or LGS
3. Weight of \>=10 kilogram (kg) at the Screening visit
4. Currently taking 1 to 4 anti-epileptic drugs (AEDs) at a stable dose
5. Failed to become and remain seizure free with trials of at least 2 AEDs

Exclusion Criteria:

1. 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
2. Non-epileptic events that cannot be reliably distinguished from epileptic seizures
3. Participation in a clinical study involving another study drug in the previous month

Primary outcomes:
measure: Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 9 to 20
Secondary outcomes:
measure: Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period
timeFrame: Baseline; Treatment Period: Weeks 0 to 20
measure: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 9 to 20
measure: Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period
timeFrame: Baseline; Maintenance Period: Weeks 9 to 20
measure: Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period
timeFrame: Maintenance Period: Weeks 9 to 20
measure: Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period
timeFrame: Maintenance Period: Weeks 9 to 20
measure: 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
timeFrame: Baseline and Week 20
measure: Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935
timeFrame: Week 20
measure: 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
timeFrame: Week 20
measure: Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy
timeFrame: Baseline and Week 24
measure: Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy
timeFrame: Baseline and Week 20
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Aurora
country: United States
facility: Colorado Children's Hospital
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurology PA
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic - PPDS
state: Minnesota
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: New Brunswick
country: United States
facility: Children's Hospital at Saint Peter's University Hospital
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Clayton
country: Australia
facility: Monash Children's Hospital
state: Victoria
city: Heidelberg West
country: Australia
facility: Austin Hospital
state: Victoria
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Capital Medical University (CMU) - Beijing Children's Hospital
city: Beijing
country: China
facility: Beijing Children's Hospital,Capital Medical University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
city: Tel Hashomer,
country: Israel
facility: Sheba Medical Center-PPDS
state: Ramat Gan
city: Bear Sheva
country: Israel
facility: Soroka University Medical Centre
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Childrens Medical Center of Israel
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne - PPDS
state: Pomorskie
city: Kielce
country: Poland
facility: NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
state: Swietokrzyskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
state: Wielkopolskie
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Warsaw
country: Poland
facility: Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
city: Warsaw
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Central- Hospital Dona Estefania
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
city: Porto
country: Portugal
facility: Largo da Maternidade de Julio DinisCentro Materno Infantil do Norte
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra
state: Navarra
city: Granada
country: Spain
facility: Hospital Vithas La Salud
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Hahn CD, Jiang Y, Villanueva V, Zolnowska M, Arkilo D, Hsiao S, Asgharnejad M, Dlugos D. A phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of soticlestat as adjunctive therapy in pediatric patients with Dravet syndrome or Lennox-Gastaut syndrome (ELEKTRA). Epilepsia. 2022 Oct;63(10):2671-2683. doi: 10.1111/epi.17367. Epub 2022 Aug 4.