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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.
 
ClinicalTrials.gov Identifier: NCT03283371
Recruitment Status : Active, not recruiting
First Posted : September 14, 2017
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE September 12, 2017
First Posted Date  ICMJE September 14, 2017
Last Update Posted Date November 27, 2020
Actual Study Start Date  ICMJE March 20, 2018
Actual Primary Completion Date January 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 21, 2020)
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Epilepsy, Focal Seizures, Partial Seizures
Intervention  ICMJE
  • Drug: Natalizumab
    As specified in the treatment arm.
    Other Name: Tysabri
  • Other: Placebo
    As specified in treatment arms.
Study Arms  ICMJE
  • 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.
    Intervention: 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.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 25, 2020)
66
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2017)
70
Estimated Study Completion Date  ICMJE December 16, 2020
Actual Primary Completion Date January 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03283371
Other Study ID Numbers  ICMJE 101EP201
2017-001995-45 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP