Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy (OPUS)
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| ClinicalTrials.gov Identifier: NCT03283371 |
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Recruitment Status :
Active, not recruiting
First Posted : September 14, 2017
Last Update Posted : September 22, 2020
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Sponsor:
Biogen
Information provided by (Responsible Party):
Biogen
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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 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 68 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 |
| Estimated Study Completion Date : | December 16, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Pyridoxal 5'-phosphate-dependent epilepsy
Autosomal dominant partial epilepsy with auditory features
Drug Information available for:
Natalizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Natalizumab
As specified in the treatment arm.
Other Name: Tysabri |
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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.
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Other: Placebo
As specified in treatment arms. |
Primary Outcome Measures :
- 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 :
- 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.
Other Outcome Measures:
- 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.
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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 |
Criteria
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 ClinicalTrials.gov identifier (NCT number): NCT03283371
Locations
| 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
Biogen
Investigators
| Study Director: | Medical Director | Biogen |
| Responsible Party: | Biogen |
| ClinicalTrials.gov Identifier: | NCT03283371 |
| Other Study ID Numbers: |
101EP201 2017-001995-45 ( EudraCT Number ) |
| First Posted: | September 14, 2017 Key Record Dates |
| Last Update Posted: | September 22, 2020 |
| Last Verified: | September 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Biogen:
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Drug Resistant Focal Epilepsy, Natalizumab, Seizure |
Additional relevant MeSH terms:
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Epilepsy Seizures Epilepsies, Partial Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Neurologic Manifestations Natalizumab Immunologic Factors Physiological Effects of Drugs |