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

Browse trials for

• Epilepsy 1,803
• Seizures 881
• Epilepsies, Partial 254

Keywords

• Drug Resistant Focal Epilepsy, Natalizumab, Seizure

Eligibility criteria

Study arms

• Experimental
  Natalizumab 300 mg

  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.

  Drug: Natalizumab

• Placebo comparator
  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.

  Other: Placebo

Interventions

• DrugNatalizumab

  As specified in the treatment arm.

  Also known as: Tysabri

• OtherPlacebo

  As specified in treatment arms.

Primary outcomes

1. 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

1. 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

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

   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.

   Time frame: Week 8 to Week 24

3. Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment

   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.

   Time frame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

4. Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment

   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.

   Time frame: Week 8 to Week 24

Other outcomes

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

   An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, in the view of the Investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect.

   Time frame: From first dose up to 24 weeks after the last dose of study treatment (up to Week 68)

2. Number of Participants With Clinically Significant Laboratory Abnormalities

   The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.

   Time frame: From first dose up to 16 weeks after the last dose of study treatment (up to Week 60)

3. Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score

   C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 1=Wish to be Dead; 2=Nonspecific Active Suicidal Thoughts; 3=Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; 4=Active Suicidal Ideation with Some Intent to Act, without Specific Plan; 5=Active Suicidal Ideation with Specific Plan and Intent; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.

   Time frame: 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)

Baseline characteristics

Publications

• 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. PubMed 34521687 ↗

Study documents

• Study protocol · May 30, 2018
• Statistical analysis plan · Feb 7, 2020

Documents are hosted by the registry — open the source record to download them.