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

Phase 2

Completed

Conditions: Epilepsy, Focal Seizures, Partial Seizures

Interventions: Drug: Natalizumab
Other: Placebo

Registration Number: NCT03283371

Lead Sponsor: Biogen

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Natalizumab 300 mg	Natalizumab	Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab 300 mg intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will continue to receive natalizumab 300 mg IV infusion every 4 weeks for up to an additional 24 weeks in open label phase.
Placebo	Placebo	Participants will undergo a prospective baseline period of 6 weeks (Weeks -6 to 0) followed by placebo controlled phase to receive natalizumab matching placebo intravenous (IV) infusion every 4 weeks from Week 0 to Week 24. Participants will then receive natalizumab 300 mg IV infusion every 4 weeks for 24 weeks in open label phase.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment	Baseline, Week 8 to Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment	Week 8 to Week 24	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.
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24	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.
Percentage of Responders During Weeks 8 to 24 of Treatment	Week 8 to Week 24	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.
Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment	Week 8 to Week 24	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.