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

Epilepsy Clinical Trial

— ELEKTRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03650452
• Other study ID #: TAK-935-2002
• Secondary ID: U1111-1206-55222
• Status: Completed
• Phase: Phase 2
• Start date: August 8, 2018
• Est. completion date: July 20, 2020

Study information

• Verified date: January 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: July 20, 2020
• Est. primary completion date: June 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Dravet Syndrome
• Epilepsies, Myoclonic
• Epilepsy
• Lennox Gastaut Syndrome
• Lennox-Gastaut Syndrome
• Syndrome

Intervention

Drug:
• TAK-935
TAK-935 tablets or mini-tablets.
• Placebo
TAK-935 placebo-matching tablets or mini-tablets.

Locations

Country	Name	City	State
Australia	Monash Children's Hospital	Clayton	Victoria
Australia	Austin Hospital	Heidelberg West	Victoria
Canada	Hospital For Sick Children	Toronto	Ontario
China	Beijing Children's Hospital,Capital Medical University	Beijing
China	Capital Medical University (CMU) - Beijing Children's Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Xiangya Hospital Central South University	Changsha
China	Children's Hospital of Fudan University	Shanghai
China	Shenzhen Children's Hospital	Shenzhen
Israel	Soroka University Medical Centre	Bear Sheva
Israel	Bnai Zion Medical Center	Haifa
Israel	Edith Wolfson Medical Center	Holon
Israel	Hadassah Medical Center	Jerusalem
Israel	Schneider Childrens Medical Center of Israel	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center-PPDS	Tel Hashomer,	Ramat Gan
Poland	Uniwersyteckie Centrum Kliniczne - PPDS	Gdansk	Pomorskie
Poland	NZOZ Centrum Neurologii Dzieciecej i Leczenia Padaczki	Kielce	Swietokrzyskie
Poland	Centrum Medyczne Plejady	Krakow
Poland	Szpital Kliniczny im. H.Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu	Poznan	Wielkopolskie
Poland	Instytut Pomnik Centrum Zdrowia Dziecka	Warsaw
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie	Warsaw
Portugal	Centro Hospitalar Lisboa Central- Hospital Dona Estefania	Lisboa
Portugal	Centro Hospitalar Lisboa Norte, E.P.E. Hospital de Santa Maria	Lisboa
Portugal	Largo da Maternidade de Julio DinisCentro Materno Infantil do Norte	Porto
Spain	Hospital Vithas La Salud	Granada
Spain	Hospital Ruber Internacional	Madrid
Spain	Clinica Universidad Navarra	Pamplona	Navarra
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Colorado Children's Hospital	Aurora	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann and Robert H Lurie Childrens Hospital of Chicago	Chicago	Illinois
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital at Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	Center for Rare Neurological Diseases	Norcross	Georgia
United States	Pediatric Neurology PA	Orlando	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Mayo Clinic - PPDS	Rochester	Minnesota
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Ovid Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Israel,  Poland,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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