Trial Outcomes & Findings for Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy (NCT NCT03283371)

Last Updated: 2021-12-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Baseline, Week 8 to Week 24

Results posted on

2021-12-14

Participant Flow

Participants were enrolled at 31 investigational sites in United States from 20 March 2018 to 18 Nov 2020.

A total 67 participants with drug-resistant focal epilepsy were enrolled and randomized in this study. Of which, 66 participants received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Placebo (Placebo-controlled Phase) Participants received natalizumab-matching placebo intravenous (IV) infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Placebo-controlled STARTED	34	33	0	0
Placebo-controlled Number of Participants Dosed	34	32	0	0
Placebo-controlled COMPLETED	31	30	0	0
Placebo-controlled NOT COMPLETED	3	3	0	0
Open-label Phase STARTED	0	0	31	30
Open-label Phase COMPLETED	0	0	27	29
Open-label Phase NOT COMPLETED	0	0	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Placebo-controlled Phase) Participants received natalizumab-matching placebo intravenous (IV) infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Placebo-controlled Adverse Event	1	1	0	0
Placebo-controlled Lack of Efficacy	1	0	0	0
Placebo-controlled Withdrawal by Subject	1	1	0	0
Placebo-controlled Participants Did Not Receive Study Drug	0	1	0	0
Open-label Phase Adverse Event	0	0	2	0
Open-label Phase Withdrawal by Subject	0	0	1	0
Open-label Phase Other	0	0	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Total n=66 Participants Total of all reporting groups
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	23 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	39.1 years STANDARD_DEVIATION 12.17 • n=5 Participants	42.8 years STANDARD_DEVIATION 14.56 • n=7 Participants	40.9 years STANDARD_DEVIATION 13.41 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8 to Week 24

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

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Change From Baseline in Log-Transformed Seizure Frequency During Weeks 8 to 24 of Treatment	-0.43 log(seizure/28 days) Standard Error 0.162	-0.58 log(seizure/28 days) Standard Error 0.165	—	—

SECONDARY outcome

Timeframe: Week 8 to Week 24

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

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Percentage of Responders During Weeks 8 to 24 of Treatment	17.6 percentage of responders	31.3 percentage of responders	—	—

SECONDARY outcome

Timeframe: Week 8 to Week 24

Population: The ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, "number of participants analyzed" signifies number of participants who were analyzed in this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=31 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Number of Participants Free From Seizures During Weeks 8 to 24 of Treatment	1 Participants	0 Participants	—	—

SECONDARY outcome

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

Population: ITT population is defined as all participants who were randomized and received any dose of study treatment. Here, "number analyzed" signifies number of participants analyzed at specific timepoint.

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.

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Baseline	16.23 percent change Standard Deviation 7.347	17.54 percent change Standard Deviation 7.223	—	—
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Week 8	4.33 percent change Standard Deviation 50.740	39.23 percent change Standard Deviation 130.988	—	—
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Week 12	2.41 percent change Standard Deviation 52.613	32.59 percent change Standard Deviation 104.775	—	—
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Week 16	-0.40 percent change Standard Deviation 43.380	44.04 percent change Standard Deviation 153.714	—	—
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Week 20	18.48 percent change Standard Deviation 101.318	40.44 percent change Standard Deviation 144.768	—	—
Percent Change From Baseline of Seizure-Free Days Change During Weeks 8 to 24 of Treatment Week 24	4.27 percent change Standard Deviation 47.125	33.92 percent change Standard Deviation 114.436	—	—

SECONDARY outcome

Timeframe: Week 8 to Week 24

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

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Percentage of Participants With Inadequate Treatment Response During Weeks 8 to 24 of Treatment	6 percentage of participants	3 percentage of participants	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.

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.

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) n=31 Participants Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) n=30 Participants Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	22 Participants	24 Participants	20 Participants	17 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	1 Participants	3 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

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

Population: The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.

The laboratory assessments included hematology, blood chemistry, serology, urinalysis and vital signs assessment.

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) n=31 Participants Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) n=30 Participants Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Number of Participants With Clinically Significant Laboratory Abnormalities	0 Participants	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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)

Population: The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.

C-SSRS is a prospective assessment tool to evaluate suicidal ideation and behavior. C-SSRS score for suicidal ideation ranges from 1 to 10, where 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; and for suicidal behavior ranges from 6=Preparatory Acts or Behavior, 7=Aborted Attempt, 8=Interrupted Attempt, 9=Actual Attempt (nonfatal), 10=Completed Suicide. Participants with a C-SSRS score between 1-10 are reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo (Placebo-controlled Phase) n=34 Participants Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo-controlled Phase) n=32 Participants Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) n=31 Participants Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) n=30 Participants Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Baseline: Suicidal Ideation or Behavior (1-10)	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 4: Suicidal Ideation or Behavior (1-10)	0 Participants	0 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 8: Suicidal Ideation or Behavior (1-10)	0 Participants	0 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 12: Suicidal Ideation or Behavior (1-10)	0 Participants	1 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 16: Suicidal Ideation or Behavior (1-10)	0 Participants	3 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 20: Suicidal Ideation or Behavior (1-10)	1 Participants	2 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 24: Suicidal Ideation or Behavior (1-10)	1 Participants	2 Participants	—	—
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 28: Suicidal Ideation or Behavior (1-10)	—	—	3 Participants	2 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 32: Suicidal Ideation or Behavior (1-10)	—	—	1 Participants	2 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 36: Suicidal Ideation or Behavior (1-10)	—	—	1 Participants	1 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 40: Suicidal Ideation or Behavior (1-10)	—	—	1 Participants	2 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 44: Suicidal Ideation or Behavior (1-10)	—	—	1 Participants	2 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 48: Suicidal Ideation or Behavior (1-10)	—	—	1 Participants	2 Participants
Number of Participants With Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) or C-SSRS Score Week 60/End of Study (EOS): Suicidal Ideation or Behavior (1-10)	—	—	0 Participants	2 Participants

Adverse Events

Placebo (Placebo-controlled Phase)

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Natalizumab 300 mg (Placebo- Controlled Phase)

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo to Natalizumab 300 mg (Open-label Phase)

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase)

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Placebo-controlled Phase) n=34 participants at risk Participants received natalizumab-matching placebo IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Natalizumab 300 mg (Placebo- Controlled Phase) n=32 participants at risk Participants received natalizumab 300 mg IV infusion every 4 weeks in Placebo-controlled Phase for up to Week 24.	Placebo to Natalizumab 300 mg (Open-label Phase) n=31 participants at risk Participants who received natalizumab-matching placebo in Placebo-controlled Phase, received natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.	Natalizumab 300 mg to Natalizumab 300 mg (Open-label Phase) n=30 participants at risk Participants who received natalizumab 300 mg in Placebo-controlled Phase, continued to receive natalizumab 300 mg IV infusion every 4 weeks in Open-label Phase for up to Week 48.
Nervous system disorders Seizure	2.9% 1/34 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.1% 1/32 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.2% 1/31 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.3% 1/30 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.
Nervous system disorders Seizure cluster	0.00% 0/34 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/32 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.2% 1/31 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/30 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.
Gastrointestinal disorders Large intestine perforation	0.00% 0/34 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/32 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/31 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.3% 1/30 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.
Infections and infestations COVID-19	0.00% 0/34 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/32 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.2% 1/31 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/30 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/34 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/32 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	0.00% 0/31 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.	3.3% 1/30 • From first dose up to 24 weeks after the last dose of study treatment (up to Week 68) The safety population is defined as all participants who were randomized and received any dose of study treatment and were used for the analysis of safety data.

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER