Epilepsy, Focal Seizures, Partial SeizuresPhase 2OPUSNCT03283371

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

A Phase 2 study testing Natalizumab in people with Epilepsy, Focal Seizures, Partial Seizures, run by Biogen at 31 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Epilepsy, Focal Seizures, Partial Seizures
What is being tested?: Natalizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 67 participants
Where: 31 sitesUnited States
Study dates: 20 Mar 2018to 18 Nov 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

31 sites in 1 country.

City, postcode or hospital

31 sites in 1 country

United States31 sites

Research Site
Akron, Ohio, 44320
Research Site
Asheville, North Carolina, 28806
Research Site
Bethesda, Maryland, 20817
Research Site
Birmingham, Alabama, 35294
Research Site
Boston, Massachusetts, 02111
Research Site
Boston, Massachusetts, 02115
Research Site
Camden, New Jersey, 08103
Research Site
Chapel Hill, North Carolina, 27514
Research Site
Charleston, South Carolina, 29425
Research Site
Chevy Chase, Maryland, 20815
Research Site
Chicago, Illinois, 60612
Research Site
Dallas, Texas, 75390
Research Site
Durham, North Carolina, 27705
Research Site
Honolulu, Hawaii, 96817
Research Site
Jacksonville, Florida, 32209
Research Site
Maitland, Florida, 32751
Research Site
Orlando, Florida, 32803
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Phoenix, Arizona, 85004
Research Site
Phoenix, Arizona, 85054
Research Site
Renton, Washington, 98055
Research Site
Rochester, New York, 14642
Research Site
Saginaw, Michigan, 48602
Research Site
San Diego, California, 92103
Research Site
Santa Monica, California, 90404
Research Site
St Louis, Missouri, 63110
Research Site
Syracuse, New York, 13210
Research Site
Tallahassee, Florida, 32308
Research Site
Tampa, Florida, 33606
Research Site
The Bronx, New York, 10467
Research Site
Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

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

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
Being tested: Natalizumab, Placebo
Keywords: Drug Resistant Focal Epilepsy, Natalizumab, Seizure
Medical subject headings: Epilepsy, Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NatalizumabDrug
Also called Tysabri
As specified in the treatment arm.
PlaceboOther
As specified in treatment arms.

Study groups in NCT03283371
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, Week 8 to Week 24

Secondary outcomes (4)

Percentage of Responders During Weeks 8 to 24 of Treatment
Responders were defined as participants with >=50% reduction from study baseline in seizure frequency during Weeks 8 to 24. Study baseline seizure frequency (number of seizures per 28 days) was calculated based on participants' seizure diary data during the prospective Baseline Phase (number of seizures during Baseline Phase/number of days with non-missing seizure frequency*28). Participants who withdrew from treatment or required protocol specified modifications of antiepileptic drug (AEDs) prior to Week 24 (completion of the Placebo-controlled Phase) or death related to Epilepsy were considered as non-responders in the analysis. Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
Measured: Week 8 to Week 24
Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment
Seizure free is defined as a participant with no seizure reported and no missing diary during Weeks 8 to 24. Participants who withdrew from treatment, required modifications of AEDs prior to Week 24 (completion of the Placebo-controlled Phase), or any missing diary data during Weeks 8 to 24 of treatment were not considered as seizure free in the analysis.
Measured: Week 8 to Week 24
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment
Study baseline seizure free days (number of seizure free days per 28 days) was calculated based on the diary data during the prospective baseline Phase (Number of seizures during baseline Phase/Number of days with non-missing seizure frequency*28). Seizure frequency at post baseline visit was calculated based on the sum of the seizures reported in the subject seizure diary and the number of days with non-missing seizure frequency data in the subject seizure diary on or after the previous visit date.
Measured: 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
Inadequate treatment response includes participants who withdraw from treatment due to lack of efficacy or require protocol specified modifications of antiepileptic drugs (AEDs) prior to Week 24 (completion of the placebo- controlled phase) or death related to Epilepsy.
Measured: Week 8 to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Mar 201818 Nov 2020

First posted14 Sep 2017
Study start20 Mar 2018
Primary completion11 Jan 2020
Study completion18 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Epilepsy, Focal Seizures, Partial SeizuresStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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 blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 67 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03283371
Sponsor's protocol ID: 101EP201
Other IDs: 2017-001995-45, 2017
Acronym: OPUS
Status last verified: Nov 2021
First submitted: 12 Sep 2017
Last updated: 14 Dec 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 34521687

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
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RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
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Enrolling by invitationPhase 3
An Open-label Study of XEN1101 in Epilepsy
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RecruitingPhase 3
A Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE3)
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RecruitingPhase 3
Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (EPIC (EPIlepsy Cell Therapy))
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All Epilepsy, Focal Seizures, Partial Seizures trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03283371
Acronym / sponsor ID: OPUS / 101EP201
Conditions: Epilepsy, Focal Seizures, Partial Seizures
Keywords: Drug Resistant Focal Epilepsy, Natalizumab, Seizure
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 67 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 20 Mar 2018 (actual)
Primary completion: 11 Jan 2020 (actual)
Study completion: 18 Nov 2020 (actual)
First posted: 14 Sep 2017 (actual)
Results: Posted 27 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2
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.

Arm	Type	Receives
Natalizumab 300 mg	Experimental	Drug: NatalizumabParticipants 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.
Placebo	Placebo comparator	Other: PlaceboParticipants 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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 (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NatalizumabAlso: TysabriAs specified in the treatment arm.	Drug	Natalizumab 300 mg
PlaceboAs specified in treatment arms.	Other	Placebo

Primary outcome

Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment
Time frame: Baseline, Week 8 to Week 24
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.

4 secondary outcomes

Percentage of Responders During Weeks 8 to 24 of Treatment
Time frame: Week 8 to Week 24
Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment
Time frame: Week 8 to Week 24
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment
Time frame: 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
Time frame: Week 8 to Week 24

Results and safety

Results posted to the registry on 27 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo (Placebo-controlled Phase)	34	31
Natalizumab 300 mg (Placebo-controlled Phase)	33	30
Placebo to Natalizumab 300 mg (Open-label Phase)	0	0
Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)	0	0

Primary outcome: Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment

Time frame: Baseline, Week 8 to Week 24. Least squares mean (Standard Error). Unit: log(seizure/28 days)

Measure	Placebo (Placebo-controlled Phase) n = 34	Natalizumab 300 mg (Placebo-controlled Phase) n = 32
Value	-0.43 (0.162)	-0.58 (0.165)

Placebo (Placebo-controlled Phase) vs Natalizumab 300 mg (Placebo-controlled Phase): LS Mean logarithmic difference: -0.16 (95% CI -0.62 to 0.31), p = 0.5053, Mixed Model for Repeated Measures (MMRM)

Population analysed: ITT population is defined as all participants who were randomized and received any dose of study treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose up to 24 weeks after the last dose of study treatment (up to Week 68). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo (Placebo-controlled Phase)	1 of 34 (2.9%)	15 of 34 (44.1%)	0 of 34
Natalizumab 300 mg (Placebo- Controlled Phase)	1 of 32 (3.1%)	17 of 32 (53.1%)	0 of 32
Placebo to Natalizumab 300 mg (Open-label Phase)	3 of 31 (9.7%)	13 of 31 (41.9%)	0 of 31
Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)	2 of 30 (6.7%)	9 of 30 (30%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34521687French 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

31 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Natalizumab in people with Epilepsy, Focal Seizures, Partial Seizures, run by Biogen at 31 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment (time frame: Baseline, Week 8 to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03283371, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2021.