Clinical trial NCT03283371: Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Exploring the Efficacy, Safety, and Tolerability of Natalizumab (BG00002) as Adjunctive Therapy in Adult Subjects With Drug-Resistant Focal Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsy, Focal Seizures, Partial Seizures
Keywords: Drug Resistant Focal Epilepsy, Natalizumab, Seizure
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-09-14
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 6-month randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of natalizumab as adjunctive therapy in the treatment of adult subjects with drug-resistant focal epilepsy. The placebo-controlled phase is followed by a 6-month open-label phase during which all subjects receive natalizumab.
Primary purpose: TREATMENT

Brief summary: The primary efficacy objective of the study is to determine if adjunctive therapy of natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult participants with drug-resistant focal epilepsy. The secondary efficacy objective is to assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on additional measures of seizure frequency.


Eligibility criteria: Key Inclusion Criteria:

* Must have focal epilepsy diagnosed on clinical grounds and as applicable supported by electroencephalogram findings \[Scheffer 2017\] and brain imaging. Participants with multifocal epilepsy may be included if all other entry criteria are met.
* Must have a drug-resistant epilepsy defined as failure of adequate trials of 2 (or more) tolerated and appropriately chosen and used AEDs (whether as monotherapies or in combination) \[Kwan 2010\].
* Experiences 6 or more seizures during the 6-week prospective baseline period and is not seizure free for more than 21 consecutive days during the prospective baseline period

Key Exclusion Criteria:

* Focal aware seizures without motor signs are the only seizure type.
* Diagnosis of generalized, combined generalized and focal, or unknown epilepsy
* Known progressive structural CNS lesion.
* History of seizures occurring in predominantly clustered patterns, as determined by the Investigator, over the 12 months prior to the Screening Visit (Week -6) or during the 6-week prospective baseline period, where individual seizures cannot be counted.
* History of status epilepticus within the previous 6 months.
* Known history or presence of non-epileptic seizures.

NOTE; Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
timeFrame: Baseline, Week 8 to Week 24
Secondary outcomes:
measure: Percentage of Responders During Weeks 8 to 24 of Treatment
timeFrame: Week 8 to Week 24
measure: Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment
timeFrame: Week 8 to Week 24
measure: Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment
timeFrame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
measure: Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment
timeFrame: Week 8 to Week 24
Other outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: From first dose up to 16 weeks after the last dose of study treatment (up to Week 60)
measure: Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score
timeFrame: Placebo-controlled Phase: Baseline, Weeks 4, 8, 12, 16, 20 and 24; Open-label Phase: Baseline, Weeks 28, 32, 36, 40, 44, 48 and 60/End of Study (EOS)
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Maitland
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tallahassee
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Chevy Chase
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saginaw
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Camden
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Syracuse
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Renton
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: French JA, Cole AJ, Faught E, Theodore WH, Vezzani A, Liow K, Halford JJ, Armstrong R, Szaflarski JP, Hubbard S, Patel J, Chen K, Feng W, Rizzo M, Elkins J, Knafler G, Parkerson KA; OPUS Study Group. Safety and Efficacy of Natalizumab as Adjunctive Therapy for People With Drug-Resistant Epilepsy: A Phase 2 Study. Neurology. 2021 Nov 2;97(18):e1757-e1767. doi: 10.1212/WNL.0000000000012766. Epub 2021 Sep 14.