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 (ELEKTRA)

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

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.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Dravet Syndrome; Lennox-Gastaut Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: TAK-935

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.

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital
    • Heidelberg West, Victoria, Australia, 3081
      • Austin Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• China
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 100045
    • Capital Medical University (CMU) - Beijing Children's Hospital
  • Beijing, China, 100069
    • Beijing Children's Hospital,Capital Medical University
  • Changsha, China, 410078
    • Xiangya Hospital Central South University
  • Shanghai, China, 201102
    • Children's Hospital of Fudan University
  • Shenzhen, China, 518026
    • Shenzhen Children's Hospital
• Israel
  • Bear Sheva, Israel, 84101
    • Soroka University Medical Centre
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Petach Tikva, Israel, 49202
    • Schneider Childrens Medical Center of Israel
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Ramat Gan
    • Tel Hashomer,, Ramat Gan, Israel, 52621
      • Sheba Medical Center-PPDS
• Poland
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Warsaw, Poland, 02-091
    • Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie
  • Warsaw, Poland, 04-730
    • Instytut Pomnik Centrum Zdrowia Dziecka
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-211
      • Uniwersyteckie Centrum Kliniczne - PPDS
  • Swietokrzyskie
    • Kielce, Swietokrzyskie, Poland, 25-316
      • NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-355
      • Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu
• Portugal
  • Lisboa, Portugal, 1169-045
    • Centro Hospitalar Lisboa Central- Hospital Dona Estefania
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria
  • Porto, Portugal, 4050-651
    • Largo da Maternidade de Julio DinisCentro Materno Infantil do Norte
• Spain
  • Granada, Spain, 18008
    • Hospital Vithas La Salud
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad Navarra
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Children's Hospital
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
    • Orlando, Florida, United States, 32819
      • Pediatric Neurology PA
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
    • Norcross, Georgia, United States, 30093
      • Center for Rare Neurological Diseases
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Childrens Hospital of Chicago
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - PPDS
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Regional Epilepsy Group
    • New Brunswick, New Jersey, United States, 08901
      • Children's Hospital at Saint Peter's University Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; TAK-935 placebo-matching tablets or mini-tablets.
Experimental: 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.	Drug: TAK-935; TAK-935 tablets or mini-tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period	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.	Baseline; Maintenance Period: Weeks 9 to 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period	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.	Baseline; Treatment Period: Weeks 0 to 20
Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period	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.	Baseline; Maintenance Period: Weeks 9 to 20
Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period	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.	Baseline; Maintenance Period: Weeks 9 to 20
Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period	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.	Maintenance Period: Weeks 9 to 20
Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period	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.	Maintenance Period: Weeks 9 to 20
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	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.	Baseline and Week 20
Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935	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.	Week 20
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	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.	Week 20
Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy	A negative change from Baseline indicates improvement.	Baseline and Week 24
Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy	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.	Baseline and Week 20

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Ovid Therapeutics Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2018
• Primary Completion (Actual): June 9, 2020
• Study Completion (Actual): July 20, 2020

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy; Nervous System Diseases; Central Nervous System Diseases; Brain Diseases; Tuberous Sclerosis; Seizure; CDKL5 deficiency disorder; Anticonvulsants; Dup15Q syndrome; Anoxic brain injury; Infantile spams; West syndrome; Cortical dysplasia; SCN1A; OV-935; Cholesterol 24S-hydroxylase inhibitor; Anti-epileptic drug; Drop seizure; Atonic seizure
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Disease; Genetic Diseases, Inborn; Epilepsy; Epilepsies, Myoclonic; Syndrome; Brain Diseases; Lennox Gastaut Syndrome
• Other Study ID Numbers: TAK-935-2002; U1111-1206-5522 (Other Identifier: World Health Organization); 2018-002484-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No