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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)

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ClinicalTrials.gov Identifier: NCT03650452
Recruitment Status : Completed
First Posted : August 28, 2018
Results First Posted : February 18, 2021
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
Ovid Therapeutics Inc.
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Epilepsy Dravet Syndrome Lennox-Gastaut Syndrome Drug: TAK-935 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 8, 2018
Actual Primary Completion Date : June 9, 2020
Actual Study Completion Date : July 20, 2020


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.




Primary Outcome Measures :
  1. Percent Change From Baseline in Seizure Frequency Per 28 Days During the Maintenance Period [ Time Frame: 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 :
  1. Percent Change From Baseline in Seizure Frequency Per 28 Days During the Treatment Period [ Time Frame: 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.

  2. Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days in Participants With Dravet Syndrome Stratum During the Maintenance Period [ Time Frame: 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.

  3. Percent Change From Baseline in Drop Seizure Frequency Per 28 Days in Participants With the Lennox-Gastaut Syndrome (LGS) Stratum During the Maintenance Period [ Time Frame: 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.

  4. Percentage of Participants With LGS Stratum Considered Treatment Responders Throughout the Maintenance Period [ Time Frame: 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.

  5. Percentage of Participants With Dravet Syndrome Stratum Considered Treatment Responders Throughout the Maintenance Period [ Time Frame: 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.

  6. 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 [ Time Frame: 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.

  7. Percentage of Participants With Clinical Global Impression of Change (CGI-C) Responses as Per the Investigator Reported Impression of Efficacy and Tolerability TAK-935 [ Time Frame: 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.

  8. 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 [ Time Frame: 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.

  9. Change From Baseline in Plasma 24S-Hydroxycholesterol (24HC) Levels in Participants Treated With TAK-935 as an Adjunctive Therapy [ Time Frame: Baseline and Week 24 ]
    A negative change from Baseline indicates improvement.

  10. Change From Baseline in Seizure Frequency in Participants Treated With TAK-935 as an Adjunctive Therapy [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03650452


Locations
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Sponsors and Collaborators
Takeda
Ovid Therapeutics Inc.
Investigators
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Study Director: Medical Director Clinical Science Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Study Protocol  [PDF] February 14, 2019
Statistical Analysis Plan  [PDF] June 15, 2020

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03650452    
Other Study ID Numbers: TAK-935-2002
U1111-1206-5522 ( Other Identifier: World Health Organization )
2018-002484-25 ( EudraCT Number )
First Posted: August 28, 2018    Key Record Dates
Results First Posted: February 18, 2021
Last Update Posted: February 18, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
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
Additional relevant MeSH terms:
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Epilepsy
Brain Diseases
Epilepsies, Myoclonic
Lennox Gastaut Syndrome
Syndrome
Disease
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Epilepsy, Generalized
Epileptic Syndromes
Genetic Diseases, Inborn