Trial Outcomes & Findings for Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis (NCT NCT01071512)

Results Overview

Cognitive function was assessed using the oral version of the Symbol Digit Modalities Test (SDMT). The number of correct responses in 90 seconds was recorded (possible range 0-110). For analysis, SDMT scores were converted to z-scores using published age and education based norms. A negative z-score indicates a SDMT score below the mean based on the age and education based norms, for example a z-score of -2 = 2 standard deviations below the mean; a positive z-score indicating a score above the mean. Higher scores indicate better cognitive function.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

20 participants

Primary outcome timeframe

Baseline, 48 weeks, 96 weeks

Results posted on

2017-10-25

Participant Flow

Participant milestones

Participant milestones
Measure	Tysabri Natalizumab 300 mg IV every 4 weeks
Overall Study STARTED	20
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Tysabri Natalizumab 300 mg IV every 4 weeks
Overall Study Adverse Event	1
Overall Study Development of antibodies to drug	2
Overall Study positive anti-JC virus antibody test	2

Baseline Characteristics

Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Race/Ethnicity, Customized African-American	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants
Age, Continuous	39 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 48 weeks, 96 weeks

Population: Summary statistics are based on the 15 subjects who completed treatment

Cognitive function was assessed using the oral version of the Symbol Digit Modalities Test (SDMT). The number of correct responses in 90 seconds was recorded (possible range 0-110). For analysis, SDMT scores were converted to z-scores using published age and education based norms. A negative z-score indicates a SDMT score below the mean based on the age and education based norms, for example a z-score of -2 = 2 standard deviations below the mean; a positive z-score indicating a score above the mean. Higher scores indicate better cognitive function.

Outcome measures

Outcome measures
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Change in Cognitive Function Over Time Baseline	-1.5 units on a scale Standard Deviation 0.9
Change in Cognitive Function Over Time Week 48	-1.2 units on a scale Standard Deviation 1.0
Change in Cognitive Function Over Time Week 96	-1.2 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline, 24, 48, 72, and 96 weeks

Population: Summary statistics are provided based on subjects completing all treatment

Retinal Nerve Fiber Layer (RNFL) thickness was measured using spectral domain OCT scans by a trained technician. Scans were performed without pupil dilation.

Outcome measures

Outcome measures
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Change Over Time in Retinal Nerve Fiber Layer Thickness Baseline	86 micrometer Standard Deviation 13
Change Over Time in Retinal Nerve Fiber Layer Thickness Week 24	85 micrometer Standard Deviation 12
Change Over Time in Retinal Nerve Fiber Layer Thickness Week 48	85 micrometer Standard Deviation 13
Change Over Time in Retinal Nerve Fiber Layer Thickness Week 72	85 micrometer Standard Deviation 13
Change Over Time in Retinal Nerve Fiber Layer Thickness Week 96	85 micrometer Standard Deviation 13

SECONDARY outcome

Timeframe: Baseline, 48 weeks, 96 weeks

Population: Summary statistics are based on subjects completing treatment

Measured based on MRI scan on a 3T Phillips scanner. This is a measure of brain atrophy (i.e., brain volume loss) with lower values indicating greater atrophy (possible range 0-1).

Outcome measures

Outcome measures
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Change Over Time in Brain Parenchymal Fraction Baseline	0.970 units on a scale Standard Deviation 0.011
Change Over Time in Brain Parenchymal Fraction Week 48	0.969 units on a scale Standard Deviation 0.012
Change Over Time in Brain Parenchymal Fraction Week 96	0.971 units on a scale Standard Deviation 0.014

SECONDARY outcome

Timeframe: Baseline, 48 weeks, 96 weeks

Population: Summary statistics are based on subjects completing all treatment

Measured on MRI scan

Outcome measures

Outcome measures
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Change Over Time in Normalized Thalamic Volume Baseline	13.9 mL Standard Deviation 1.9
Change Over Time in Normalized Thalamic Volume Week 48	13.7 mL Standard Deviation 2.0
Change Over Time in Normalized Thalamic Volume Week 96	13.7 mL Standard Deviation 2.1

SECONDARY outcome

Timeframe: Baseline, 48 weeks, 96 weeks

Population: Summary statistics are based on subjects completing all treatment

Measured on MRI scan

Outcome measures

Outcome measures
Measure	Tysabri n=15 Participants Natalizumab 300 mg IV every 4 weeks
Change Over Time in Normalized Hippocampal Volume Baseline	6.8 mL Standard Deviation 0.8
Change Over Time in Normalized Hippocampal Volume Week 48	6.7 mL Standard Deviation 1.0
Change Over Time in Normalized Hippocampal Volume Week 96	6.6 mL Standard Deviation 0.9

Adverse Events

Tysabri

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tysabri n=20 participants at risk Natalizumab 300 mg IV every 4 weeks
Skin and subcutaneous tissue disorders pruritis	5.0% 1/20 • 96 weeks

Additional Information

Dr. Adil Javed

University of Chicago

Phone: 773.834.0558

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place