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

NCT00368251 | Completed Phase 3 Results

• 2 other identifiers: N012362006-001536-46
• Study Type: interventional
• Target: 56
• Locations: 8 countries
• Sites: 18

Brief Summary

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

Conditions

Unverricht-Lundborg Disease

Keywords

Unverricht-Lundborg Disease; Baltic Myoclonus; Progressive Myoclonic Epilepsies; Myoclonus; Brivaracetam

Outcome Measures

Primary Outcomes (1)

• 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.

  From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)

Secondary Outcomes (4)

• Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)

  Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)

• Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)

  Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)

• Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)

  Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)

• Global Evaluation Score (Investigator) at the End of Treatment Period

  End of Treatment Period (Week 14 or Early Discontinuation Visit)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Brivaracetam 5 mg/day

EXPERIMENTAL

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)

Drug: BRV 2.5 mg

Brivaracetam 150 mg/day

EXPERIMENTAL

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)

Drug: BRV 25 mg; Drug: BRV 50 mg

Interventions

Placebo OTHER

* Pharmaceutical Form: Tablet * Concentration: 2.5 mg, 25 mg and 50 mg * Route of Administration: Oral use

Placebo

BRV 25 mg DRUG

* Pharmaceutical Form: Tablet * Concentration: 25 mg * Route of Administration: Oral use

Brivaracetam 150 mg/day

BRV 50 mg DRUG

* Pharmaceutical Form: Tablet * Concentration: 50 mg * Route of Administration: Oral use

Brivaracetam 150 mg/day

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• UCB Pharma: lead

Study Sites (18)

135

San Francisco, California, United States

Location

133

Gainesville, Florida, United States

Location

132

New York, New York, United States

Location

131

Charlottesville, Virginia, United States

Location

151

Vancouver, British Columbia, Canada

Location

150

Montreal, Quebec, Canada

Location

152

Québec, Quebec, Canada

Location

100

Helsinki, Finland

Location

122

Bron, France

Location

121

Lille, France

Location

120

Paris, France

Location

170

Tel Aviv, Israel

Location

141

Moscow, Russia

Location

142

Saint Petersburg, Russia

Location

143

Samara, Russia

Location

161

Belgrade, Serbia

Location

162

Belgrade, Serbia

Location

180

Manouba, Tunisia

Location

Related Publications (2)

• 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.

  PMID: 33461041 DERIVED

• 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.

  PMID: 26666500 DERIVED

Related Links

• Product Information
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Unverricht-Lundborg Syndrome; Myoclonic Epilepsies, Progressive; Myoclonus

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: UCB Cares
• Organization: UCB

+1877 822

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 23, 2006
• First Posted: August 24, 2006
• Study Start: November 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: May 31, 2023
• Results First Posted: April 13, 2016

Record last verified: 2023-05

Locations

RU (3); FR (3); IL (1); FI (1); US (4); CA (3); TU (1); SE (2)