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.
Brief Title
Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy
Categories
Completion Date
Completion Date Type
Actual
Conditions
Epilepsy, Focal Seizures, Partial Seizures
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
* 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
Inclusion Criteria
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
Inclusion/
* 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
Inclusion/
Gender
All
Gender Based
false
Keywords
Drug Resistant Focal Epilepsy, Natalizumab, Seizure
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT03283371
Org Class
Industry
Org Full Name
Biogen
Org Study Id
101EP201
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Seizures included were focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizure. Focal aware seizures without motor signs were not included. Seizure clusters (where individual seizures cannot be distinguished) were counted as 1 seizure per cluster on each day that they are present. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participant's seizure diary data during prospective baseline phase. Seizure frequency (SF) at post baseline visit was calculated based on sum of the seizures reported in participant seizure diary and the number of days with non-missing SF data in participant seizure diary on or after the previous visit date. Change from Baseline are based on natural log transformation of baseline SF or SF at post baseline visit correspondingly. For log-transformation, the quantity 0.2 {ln(x+0.2)} was added to the SF at post baseline visit to account for 0 seizure count.
Outcome Measure
Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
Outcome Time Frame
Baseline, Week 8 to Week 24
Secondary Ids
Secondary Id
2017-001995-45
Secondary Outcomes
Outcome Description
Responders were defined as participants with \>=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency\*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
Outcome Time Frame
Week 8 to Week 24
Outcome Measure
Percentage of Responders During Weeks 8 to 24 of Treatment
Outcome Description
Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.
Outcome Time Frame
Week 8 to Week 24
Outcome Measure
Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment
Outcome Description
Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency\*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
Outcome Time Frame
Baseline, Week 8, Week 12, Week 16, Week 20, Week 24
Outcome Measure
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment
Outcome Description
Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.
Outcome Time Frame
Week 8 to Week 24
Outcome Measure
Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alexis Boro
Investigator Email
aboro@montefiore.org
Investigator Phone