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.|
|ClinicalTrials.gov Identifier: NCT03283371|
Recruitment Status : Active, not recruiting
First Posted : September 14, 2017
Last Update Posted : September 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|Epilepsy, Focal Seizures, Partial Seizures||Drug: Natalizumab Other: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||68 participants|
|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)|
|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|
|Estimated Study Completion Date :||December 16, 2020|
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.
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.
As specified in treatment arms.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Number of Participants with Clinically Significant Laboratory Abnormalities [ Time Frame: Up to Week 60 ]
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03283371
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|United States, Arizona|
|Phoenix, Arizona, United States, 85004|
|Phoenix, Arizona, United States, 85054|
|United States, California|
|San Diego, California, United States, 92103|
|Santa Monica, California, United States, 90404|
|United States, District of Columbia|
|Washington, District of Columbia, United States, 20037|
|United States, Florida|
|Jacksonville, Florida, United States, 32209|
|Maitland, Florida, United States, 32751|
|Orlando, Florida, United States, 32803|
|Tallahassee, Florida, United States, 32308|
|Tampa, Florida, United States, 33606|
|United States, Hawaii|
|Honolulu, Hawaii, United States, 96817|
|United States, Illinois|
|Chicago, Illinois, United States, 60612|
|United States, Maryland|
|Bethesda, Maryland, United States, 20817|
|Chevy Chase, Maryland, United States, 20815|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02111|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|Saginaw, Michigan, United States, 48602|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Camden, New Jersey, United States, 08103|
|United States, New York|
|Bronx, New York, United States, 10467|
|Rochester, New York, United States, 14642|
|Syracuse, New York, United States, 13210|
|United States, North Carolina|
|Asheville, North Carolina, United States, 28806|
|Chapel Hill, North Carolina, United States, 27514|
|Durham, North Carolina, United States, 27705|
|United States, Ohio|
|Akron, Ohio, United States, 44320|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, South Carolina|
|Charleston, South Carolina, United States, 29425|
|United States, Texas|
|Dallas, Texas, United States, 75390|
|United States, Washington|
|Renton, Washington, United States, 98055|
|Study Director:||Medical Director||Biogen|