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

NCT03283371 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 101EP2012017-001995-45
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 31

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.

Conditions

Epilepsy, Focal Seizures, Partial Seizures

Keywords

Drug Resistant Focal Epilepsy, Natalizumab, Seizure

Outcome Measures

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.

  Baseline, Week 8 to Week 24

Secondary Outcomes (4)

• Percentage of Responders During Weeks 8 to 24 of Treatment

  Week 8 to Week 24

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

  Week 8 to Week 24

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

  Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

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

  Week 8 to Week 24

Other Outcomes (3)

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

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

• Number of Participants With Clinically Significant Laboratory Abnormalities

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

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

  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)

Study Arms (2)

Natalizumab 300 mg

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Natalizumab DRUG

As specified in the treatment arm.

Also known as: Tysabri

Natalizumab 300 mg

Placebo OTHER

As specified in treatment arms.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (31)

Research Site

Birmingham, Alabama, 35294, United States

Location

Research Site

Phoenix, Arizona, 85004, United States

Location

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Phoenix, Arizona, 85054, United States

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San Diego, California, 92103, United States

Location

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Santa Monica, California, 90404, United States

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Washington D.C., District of Columbia, 20037, United States

Location

Research Site

Jacksonville, Florida, 32209, United States

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Research Site

Maitland, Florida, 32751, United States

Location

Research Site

Orlando, Florida, 32803, United States

Location

Research Site

Tallahassee, Florida, 32308, United States

Location

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Tampa, Florida, 33606, United States

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Honolulu, Hawaii, 96817, United States

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Chicago, Illinois, 60612, United States

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Bethesda, Maryland, 20817, United States

Location

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Chevy Chase, Maryland, 20815, United States

Location

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Boston, Massachusetts, 02111, United States

Location

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Boston, Massachusetts, 02115, United States

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Saginaw, Michigan, 48602, United States

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St Louis, Missouri, 63110, United States

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Camden, New Jersey, 08103, United States

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Rochester, New York, 14642, United States

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Syracuse, New York, 13210, United States

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The Bronx, New York, 10467, United States

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Asheville, North Carolina, 28806, United States

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Chapel Hill, North Carolina, 27514, United States

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Durham, North Carolina, 27705, United States

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Akron, Ohio, 44320, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29425, United States

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Dallas, Texas, 75390, United States

Location

Research Site

Renton, Washington, 98055, United States

Location

Related Publications (1)

• 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.

  PMID: 34521687 DERIVED

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: March 20, 2018
• Primary Completion: January 11, 2020
• Study Completion: November 18, 2020
• Last Updated: December 14, 2021
• Results First Posted: April 27, 2021

Record last verified: 2021-11

Locations

US (31)