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Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults

Primary Purpose

Unverricht-Lundborg Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
BRV 2.5 mg
BRV 25 mg
BRV 50 mg
Sponsored by
UCB Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unverricht-Lundborg Disease focused on measuring Unverricht-Lundborg Disease, Baltic Myoclonus, Progressive Myoclonic Epilepsies, Myoclonus, Brivaracetam

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: - Subjects with diagnosed Unverricht-Lundborg disease (ULD) ascertained by appropriate genetic testing for a homozygous or compound heterozygous mutation in the CSTB gene- Subjects with moderate to severe myoclonus documented by an Action Myoclonussum score of ≥ 30 (evaluation by investigator)-Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator- Subjects currently being or having been treated with valproate up to the maximum recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator- Male/female subjects from 16 years onwards. Subjects under 18 years may only be included where legally permitted and ethically accepted Exclusion Criteria: - Subjects currently on felbamate or having been on felbamate within less than 18 months prior to Visit 1- Subjects currently treated with phenytoin or having been on phenytoin in the last month prior to Visit 1- Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual fields examination report available including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman)- Subject taking any drug with possible central nervous system (CNS) effects- Subjects taking any drug that may significantly influence the metabolism of BRV (CYP2C or CYP3A potent inducers/inhibitors)- Known clinically significant acute or chronic illness or illness which may impair reliable participation in the trial, necessitate the use of medication not allowed by protocol or represent a safety risk in the Investigator's opinion- Subjects with history of severe adverse hematological reaction to any drug- Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT value of more than three times the upper limit of the reference range- History of suicide attempt during the last 5 years- Subject with suicidal ideations within the last year or at risk of suicide attempt unless cleared by written confirmation from a psychiatrist and approved by the UCB physician- Ongoing psychiatric disorder other than mild controlled disorder

Sites / Locations

  • 135
  • 133
  • 132
  • 131
  • 151
  • 150
  • 152
  • 100
  • 122
  • 121
  • 120
  • 170
  • 141
  • 142
  • 143
  • 161
  • 162
  • 180

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Brivaracetam 5 mg/day

Brivaracetam 150 mg/day

Arm Description

Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period)

Brivaracetam (BRV) 5 mg/day 5 mg twice a day (bid) using 2.5 mg tablets for 12 weeks (after 2 week Up- Titration Period)

Brivaracetam (BRV) 150 mg/day 150 mg twice a day (bid) using 25 mg and 50 mg tablets for 12 weeks (after 2 week Up-Titration Period)

Outcomes

Primary Outcome Measures

Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)
The range for Action Myoclonus Score (centrally read) is 0 (best) - 160 (worst). Percent change from Baseline = 100 X ((Baseline UMRS4 - Treatment UMRS4) / Baseline UMRS4). Baseline is defined as the last non-missing value prior to or on Randomization Visit.

Secondary Outcome Measures

Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)
The range for Functional Disability Score is 0 (best) to 28 (worst). Percent change from Baseline = 100 X ((Baseline UMRS5 - Treatment UMRS5) / Baseline UMRS5). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)
The range for Stimulus Sensitivity Score is 0 (best) to 17 (worst). Percent change from Baseline = 100 X ((Baseline UMRS3 - Treatment UMRS3) / Baseline UMRS3). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)
The range for Myoclonus Patient Questionnaire is 0 (best) to 44 (worst). Percent change from Baseline = 100 X ((Baseline UMRS1 - Treatment UMRS1) / Baseline UMRS1). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Global Evaluation Score (Investigator) at the End of Treatment Period
The Global Evaluation Scale Score (Investigator) ranges from 1 (Marked worsening) to 7 (Marked improvement).

Full Information

First Posted
August 23, 2006
Last Updated
May 3, 2023
Sponsor
UCB Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT00368251
Brief Title
Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study to Evaluate the Efficacy and Safety of Brivaracetam Used as Adjunctive Treatment for 12 Weeks in Adolescent and Adult Patients (≥ 16 Years) With Genetically Ascertained Unverricht-Lundborg Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Pharma

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unverricht-Lundborg Disease
Keywords
Unverricht-Lundborg Disease, Baltic Myoclonus, Progressive Myoclonic Epilepsies, Myoclonus, Brivaracetam

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period)
Arm Title
Brivaracetam 5 mg/day
Arm Type
Experimental
Arm Description
Brivaracetam (BRV) 5 mg/day 5 mg twice a day (bid) using 2.5 mg tablets for 12 weeks (after 2 week Up- Titration Period)
Arm Title
Brivaracetam 150 mg/day
Arm Type
Experimental
Arm Description
Brivaracetam (BRV) 150 mg/day 150 mg twice a day (bid) using 25 mg and 50 mg tablets for 12 weeks (after 2 week Up-Titration Period)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical Form: Tablet Concentration: 2.5 mg, 25 mg and 50 mg Route of Administration: Oral use
Intervention Type
Drug
Intervention Name(s)
BRV 2.5 mg
Other Intervention Name(s)
ucb34714
Intervention Description
Pharmaceutical Form: Tablet Concentration: 2.5 mg Route of Administration: Oral use
Intervention Type
Drug
Intervention Name(s)
BRV 25 mg
Intervention Description
Pharmaceutical Form: Tablet Concentration: 25 mg Route of Administration: Oral use
Intervention Type
Drug
Intervention Name(s)
BRV 50 mg
Intervention Description
Pharmaceutical Form: Tablet Concentration: 50 mg Route of Administration: Oral use
Primary Outcome Measure Information:
Title
Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)
Description
The range for Action Myoclonus Score (centrally read) is 0 (best) - 160 (worst). Percent change from Baseline = 100 X ((Baseline UMRS4 - Treatment UMRS4) / Baseline UMRS4). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Time Frame
From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Secondary Outcome Measure Information:
Title
Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)
Description
The range for Functional Disability Score is 0 (best) to 28 (worst). Percent change from Baseline = 100 X ((Baseline UMRS5 - Treatment UMRS5) / Baseline UMRS5). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Time Frame
Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Title
Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)
Description
The range for Stimulus Sensitivity Score is 0 (best) to 17 (worst). Percent change from Baseline = 100 X ((Baseline UMRS3 - Treatment UMRS3) / Baseline UMRS3). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Time Frame
Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Title
Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)
Description
The range for Myoclonus Patient Questionnaire is 0 (best) to 44 (worst). Percent change from Baseline = 100 X ((Baseline UMRS1 - Treatment UMRS1) / Baseline UMRS1). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Time Frame
Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Title
Global Evaluation Score (Investigator) at the End of Treatment Period
Description
The Global Evaluation Scale Score (Investigator) ranges from 1 (Marked worsening) to 7 (Marked improvement).
Time Frame
End of Treatment Period (Week 14 or Early Discontinuation Visit)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Subjects with diagnosed Unverricht-Lundborg disease (ULD) ascertained by appropriate genetic testing for a homozygous or compound heterozygous mutation in the CSTB gene- Subjects with moderate to severe myoclonus documented by an Action Myoclonussum score of ≥ 30 (evaluation by investigator)-Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator- Subjects currently being or having been treated with valproate up to the maximum recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator- Male/female subjects from 16 years onwards. Subjects under 18 years may only be included where legally permitted and ethically accepted Exclusion Criteria: - Subjects currently on felbamate or having been on felbamate within less than 18 months prior to Visit 1- Subjects currently treated with phenytoin or having been on phenytoin in the last month prior to Visit 1- Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual fields examination report available including standard static (Humphrey or Octopus) or cinetic perimetry (Goldman)- Subject taking any drug with possible central nervous system (CNS) effects- Subjects taking any drug that may significantly influence the metabolism of BRV (CYP2C or CYP3A potent inducers/inhibitors)- Known clinically significant acute or chronic illness or illness which may impair reliable participation in the trial, necessitate the use of medication not allowed by protocol or represent a safety risk in the Investigator's opinion- Subjects with history of severe adverse hematological reaction to any drug- Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT value of more than three times the upper limit of the reference range- History of suicide attempt during the last 5 years- Subject with suicidal ideations within the last year or at risk of suicide attempt unless cleared by written confirmation from a psychiatrist and approved by the UCB physician- Ongoing psychiatric disorder other than mild controlled disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
+1 877 822 9493 (UCB)
Official's Role
Study Director
Facility Information:
Facility Name
135
City
San Francisco
State/Province
California
Country
United States
Facility Name
133
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
132
City
New York
State/Province
New York
Country
United States
Facility Name
131
City
Charlottesville
State/Province
Virginia
Country
United States
Facility Name
151
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
150
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
152
City
Quebec
Country
Canada
Facility Name
100
City
Helsinki
Country
Finland
Facility Name
122
City
Bron
Country
France
Facility Name
121
City
Lille
Country
France
Facility Name
120
City
Paris
Country
France
Facility Name
170
City
Tel Aviv
Country
Israel
Facility Name
141
City
Moscow
Country
Russian Federation
Facility Name
142
City
Saint Petersburg
Country
Russian Federation
Facility Name
143
City
Samara
Country
Russian Federation
Facility Name
161
City
Belgrade
Country
Serbia
Facility Name
162
City
Belgrade
Country
Serbia
Facility Name
180
City
La Manouba
Country
Tunisia

12. IPD Sharing Statement

Citations:
PubMed Identifier
33461041
Citation
Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C. Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial. Epilepsy Res. 2021 Feb;170:106526. doi: 10.1016/j.eplepsyres.2020.106526. Epub 2020 Dec 4.
Results Reference
derived
PubMed Identifier
26666500
Citation
Kalviainen R, Genton P, Andermann E, Andermann F, Magaudda A, Frucht SJ, Schlit AF, Gerard D, de la Loge C, von Rosenstiel P. Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 2016 Feb;57(2):210-21. doi: 10.1111/epi.13275. Epub 2015 Dec 15.
Results Reference
derived
Links:
URL
https://www.briviact.com/briviact-PI.pdf?v=1479491757
Description
Product Information
URL
http://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults

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