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Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

Primary Purpose

Dravet Syndrome

Status
Withdrawn
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Clobazam
Placebo
Sponsored by
H. Lundbeck A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dravet Syndrome

Eligibility Criteria

1 Year - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Onset of seizures in the first year of life
  • History of fever-induced prolonged seizures as determined by the Investigator
  • These may include prolonged (approximately 15 minutes or longer) hemi-clonic seizures

  • Multiple seizure types which may include:

    • generalised tonic-clonic (required for inclusion)
    • clonic (required for inclusion)
    • myoclonic jerks/seizures
    • history of normal development prior to seizure onset followed by development delay or regression after seizure onset
    • abnormal EEG consistent with Dravet Syndrome 2. The patient has a history of approximately 2 tonic-clonic or clonic seizures in 2 weeks 3. The patient is treated with at least 1 but no more than 3 antiepileptic drugs (AEDs) [Vagal Nerve Stimulator (VNS) and ketogenic diet will not be considered an AED] 4. Patient has at least 2 seizures during the Baseline Period of either 2 or 4 weeks

Exclusion Criteria:

  1. The patient is taking stiripentol, verapamil, or felbatol. If patients have taken these drugs in the past, they need to have been off drug for 5 half-lives
  2. The patient is taking a sodium channel blocker including, but not limited to, phenytoin, fosphenytoin, carbamazepine, oxcarbamazepine, lamotrigine, lacosamide, and rufinamide. If patients have taken these drugs in the past, they need to have been off drug for 5 half-lives
  3. The patient is on cannabidiol, medical marijuana, or any drug that contains cannabinoids
  4. The patient has received chronic treatment (≥2 weeks for any indication) with a benzodiazepine within at least 5 half-lives prior to screening. Rescue therapy for prolonged seizures is allowed
  5. The patient has received clobazam within 3 months prior to the Screening Visit. If the patient has received clobazam in the past, discontinuation must not have been for adverse events or lack of efficacy

Other protocol-defined inclusion and exclusion criteria may apply.

Sites / Locations

  • US010
  • US001
  • US003
  • US005
  • US006
  • US0011
  • US002
  • US004
  • MX003

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Clobazam

Placebo

Arm Description

Clobazam - 1.0, 1.5 or 2.0 mg/kg/day (maximum 60 or 80 mg/day) twice daily (BID); Clobazam oral suspension 2.5 mg/mL, clobazam scored tablets 10 mg, orally

Placebo to clobazam oral suspension 2.5 mg/mL and placebo to clobazam scored tablets 10 mg, orally

Outcomes

Primary Outcome Measures

Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts

Secondary Outcome Measures

Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts during 4 weeks of maintenance
Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts
Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts
Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts
Percent change in seizure rate for all seizure types determined from daily seizure diary counts
Number of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
Percentage of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
Percent change in seizure rate for myoclonic seizures determined from video EEG
Percent change in seizure rate for atypical absence seizures determined from video EEG
Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Columbia Suicide Severity Rating Scale (C-SSRS), categorisation based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories (1, 2, 3, 4 and 7) for patients aged ≥ 6 years
Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose
Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors

Full Information

First Posted
June 2, 2014
Last Updated
September 23, 2015
Sponsor
H. Lundbeck A/S
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1. Study Identification

Unique Protocol Identification Number
NCT02174094
Brief Title
Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
Official Title
Multi-site, Prospective, Randomised, Double-blind, Placebo-controlled, Parallel-group, Interventional Study to Evaluate the Efficacy, Safety, and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Withdrawn
Why Stopped
The study was terminated due to recruitment challenges
Study Start Date
March 2015 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lundbeck A/S

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to investigate the effect on the frequency of tonic-clonic and clonic seizures of clobazam as adjunctive therapy compared to placebo after 16 weeks of treatment in paediatric patients aged ≥1 to ≤16 years with Dravet Syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dravet Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clobazam
Arm Type
Experimental
Arm Description
Clobazam - 1.0, 1.5 or 2.0 mg/kg/day (maximum 60 or 80 mg/day) twice daily (BID); Clobazam oral suspension 2.5 mg/mL, clobazam scored tablets 10 mg, orally
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to clobazam oral suspension 2.5 mg/mL and placebo to clobazam scored tablets 10 mg, orally
Intervention Type
Drug
Intervention Name(s)
Clobazam
Other Intervention Name(s)
Onfi®
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts
Time Frame
Baseline and from week 0 to week 16
Secondary Outcome Measure Information:
Title
Percent change from baseline to study completion/withdrawal in seizure rate for combined tonic-clonic and clonic seizure rates, based upon a calculation of seizure frequency determined from daily seizure diary counts during 4 weeks of maintenance
Time Frame
Baseline and from week 4 to week 16
Title
Percent change in seizure rate for myoclonic seizures determined from daily seizure diary counts
Time Frame
Baseline and from week 0 to week 16
Title
Percent change in seizure rate for atypical absence seizures determined from daily seizure diary counts
Time Frame
Baseline and from week 0 to week 16
Title
Percent change in seizure rate for complex partial seizures determined from daily seizure diary counts
Time Frame
Baseline and from week 0 to week 16
Title
Percent change in seizure rate for all seizure types determined from daily seizure diary counts
Time Frame
Baseline and from week 0 to week 16
Title
Number of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
Time Frame
Baseline and from week 0 to week 16
Title
Percentage of initial treatment responders who returned to their baseline tonic-clonic and clonic seizure rate during the study (an assessment of tachyphylaxis)
Time Frame
Baseline and from week 0 to week 16
Title
Percent change in seizure rate for myoclonic seizures determined from video EEG
Time Frame
Baseline and from week 0 to week 16
Title
Percent change in seizure rate for atypical absence seizures determined from video EEG
Time Frame
Baseline and from week 0 to week 16
Title
Change in Symptom and Seizure Activity Scale (Investigator and Parent/caregiver versions)
Time Frame
Baseline and from week 0 to week 16
Title
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame
Up to Week 32
Title
Columbia Suicide Severity Rating Scale (C-SSRS), categorisation based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories (1, 2, 3, 4 and 7) for patients aged ≥ 6 years
Time Frame
Baseline and from week 0 to week 16
Title
Number of Participants with Adverse Events of special interest as a Measure of Safety and Tolerability based on dose
Time Frame
Baseline and Week 32
Title
Change in Vineland Adaptive Behaviour Scale (VABS) - all adaptive behavior sub-domains and maladaptive behaviors
Time Frame
Baseline and from week 0 to week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Onset of seizures in the first year of life History of fever-induced prolonged seizures as determined by the Investigator These may include prolonged (approximately 15 minutes or longer) hemi-clonic seizures Multiple seizure types which may include: generalised tonic-clonic (required for inclusion) clonic (required for inclusion) myoclonic jerks/seizures history of normal development prior to seizure onset followed by development delay or regression after seizure onset abnormal EEG consistent with Dravet Syndrome 2. The patient has a history of approximately 2 tonic-clonic or clonic seizures in 2 weeks 3. The patient is treated with at least 1 but no more than 3 antiepileptic drugs (AEDs) [Vagal Nerve Stimulator (VNS) and ketogenic diet will not be considered an AED] 4. Patient has at least 2 seizures during the Baseline Period of either 2 or 4 weeks Exclusion Criteria: The patient is taking stiripentol, verapamil, or felbatol. If patients have taken these drugs in the past, they need to have been off drug for 5 half-lives The patient is taking a sodium channel blocker including, but not limited to, phenytoin, fosphenytoin, carbamazepine, oxcarbamazepine, lamotrigine, lacosamide, and rufinamide. If patients have taken these drugs in the past, they need to have been off drug for 5 half-lives The patient is on cannabidiol, medical marijuana, or any drug that contains cannabinoids The patient has received chronic treatment (≥2 weeks for any indication) with a benzodiazepine within at least 5 half-lives prior to screening. Rescue therapy for prolonged seizures is allowed The patient has received clobazam within 3 months prior to the Screening Visit. If the patient has received clobazam in the past, discontinuation must not have been for adverse events or lack of efficacy Other protocol-defined inclusion and exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H. Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@lundbeck.com
Official's Role
Study Director
Facility Information:
Facility Name
US010
City
Los Angeles
State/Province
California
Country
United States
Facility Name
US001
City
Orlando
State/Province
Florida
Country
United States
Facility Name
US003
City
Rochester
State/Province
Minnesota
Country
United States
Facility Name
US005
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
US006
City
Dallas,
State/Province
Texas
Country
United States
Facility Name
US0011
City
Dallas
State/Province
Texas
Country
United States
Facility Name
US002
City
Houston
State/Province
Texas
Country
United States
Facility Name
US004
City
Seattle
State/Province
Washington
Country
United States
Facility Name
MX003
City
Guadalajara
Country
Mexico

12. IPD Sharing Statement

Learn more about this trial

Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome

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