Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy

Biogen67 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Epilepsy, Focal Seizures, Partial Seizures

Interventions

NatalizumabDRUG

As specified in the treatment arm.

PlaceboOTHER

As specified in treatment arms.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (31)

Outcomes

Primary Outcomes

Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment

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.

Time frame: Baseline, Week 8 to Week 24

Secondary Outcomes

Percentage of Responders During Weeks 8 to 24 of Treatment

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.

Time frame: Week 8 to Week 24

Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment

Data from ClinicalTrials.gov

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