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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03283371
Recruitment Status : Completed
First Posted : September 14, 2017
Last Update Posted : December 23, 2020
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Epilepsy, Focal Seizures, Partial Seizures Drug: Natalizumab Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2018
Actual Primary Completion Date : January 10, 2020
Actual Study Completion Date : November 18, 2020

Arm Intervention/treatment
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
As specified in the treatment arm.
Other Name: Tysabri

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
As specified in treatment arms.

Primary Outcome Measures :
  1. Change from Baseline in Log-Transformed Seizure Frequency during Weeks 8 to 24 of Treatment [ Time Frame: Week 8 to Week 24 ]

    Seizures included in efficacy analyses are focal aware seizures (previously termed "simple partial seizures") with motor signs, focal impaired awareness seizures (previously termed "complex partial seizures"), and focal to bilateral tonic-clonic seizures (previously termed "partial onset with secondary generalization"). Focal aware seizures without motor signs will not be included.

    Seizure clusters (where individual seizures cannot be distinguished) will be counted as 1 seizure per cluster on each day that they are present.

Secondary Outcome Measures :
  1. Percentage of Responders [ Time Frame: Week 8 to Week 24 ]
    Responders were defined as participants with a ≥50% reduction from Baseline in seizure frequency (number of seizures per 28 days) during Weeks 8 to 24 of treatment.

  2. Percentage of Participants Free from Seizures [ Time Frame: Week 8 to Week 24 ]
    Proportion of subjects free from seizures during Weeks 8 to 24 of treatment.

  3. Percentage of Seizure-Free Days Gained [ Time Frame: Week 8 to Week 24 ]
    Seizure free days gained will be standardized over 28 days during weeks 8 to 24 of treatment compared with baseline.

  4. Percentage of Participants with Inadequate Treatment Response [ Time Frame: Week 8 to Week 24 ]
    Inadequate treatment response will be defined as either modification of anti-epileptic drugs (AEDs) after Week 12 of the placebo-controlled phase due to lack of improvement or ongoing seizures or discontinuation of study treatment after the 8-week active run-in period due to lack of efficacy.

Other Outcome Measures:
  1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 68 ]
    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.

  2. Number of Participants with Clinically Significant Laboratory Abnormalities [ Time Frame: Up to Week 60 ]
  3. Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score [ Time Frame: Up to Week 60 ]
    C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation and behavior ranges from 0 to 10, where 0=No any suicidal ideation/behavior; 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; 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03283371

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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35294
United States, Arizona
Research Site
Phoenix, Arizona, United States, 85004
Research Site
Phoenix, Arizona, United States, 85054
United States, California
Research Site
San Diego, California, United States, 92103
Research Site
Santa Monica, California, United States, 90404
United States, District of Columbia
Research Site
Washington, District of Columbia, United States, 20037
United States, Florida
Research Site
Jacksonville, Florida, United States, 32209
Research Site
Maitland, Florida, United States, 32751
Research Site
Orlando, Florida, United States, 32803
Research Site
Tallahassee, Florida, United States, 32308
Research Site
Tampa, Florida, United States, 33606
United States, Hawaii
Research Site
Honolulu, Hawaii, United States, 96817
United States, Illinois
Research Site
Chicago, Illinois, United States, 60612
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20817
Research Site
Chevy Chase, Maryland, United States, 20815
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02111
Research Site
Boston, Massachusetts, United States, 02115
United States, Michigan
Research Site
Saginaw, Michigan, United States, 48602
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Research Site
Camden, New Jersey, United States, 08103
United States, New York
Research Site
Bronx, New York, United States, 10467
Research Site
Rochester, New York, United States, 14642
Research Site
Syracuse, New York, United States, 13210
United States, North Carolina
Research Site
Asheville, North Carolina, United States, 28806
Research Site
Chapel Hill, North Carolina, United States, 27514
Research Site
Durham, North Carolina, United States, 27705
United States, Ohio
Research Site
Akron, Ohio, United States, 44320
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29425
United States, Texas
Research Site
Dallas, Texas, United States, 75390
United States, Washington
Research Site
Renton, Washington, United States, 98055
Sponsors and Collaborators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen Identifier: NCT03283371    
Other Study ID Numbers: 101EP201
2017-001995-45 ( EudraCT Number )
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: December 23, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biogen:
Drug Resistant Focal Epilepsy, Natalizumab, Seizure
Additional relevant MeSH terms:
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Epilepsies, Partial
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Immunologic Factors
Physiological Effects of Drugs