Trial Outcomes & Findings for A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients (NCT NCT00871780)

NCT ID: NCT00871780

Last Updated: 2017-03-21

Results Overview

In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 224 participants
• Primary outcome timeframe: Baseline, Week 24, Week 48
• Results posted on: 2017-03-21

Participant Flow

Participant milestones

Measure	Natalizumab natalizumab 300 mg IV every 4 weeks for 48 weeks
Overall Study STARTED	224
Overall Study Safety Analysis Population	218
Overall Study Efficacy Analysis Population	215
Overall Study COMPLETED	197
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Measure	Natalizumab natalizumab 300 mg IV every 4 weeks for 48 weeks
Overall Study Enrolled But Not Treated	6
Overall Study Withdrawal by Subject	9
Overall Study Adverse Event	6
Overall Study Voluntary Discontinuation	4
Overall Study Death	1
Overall Study Physician Decision	1

Baseline Characteristics

A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients

Baseline characteristics by cohort

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks
Age, Continuous	35.1 years STANDARD_DEVIATION 9.56 • n=5 Participants
Sex: Female, Male Female	137 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data at given time point.

In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Change From Baseline in the Timed 100-meter Walk Test (T100T) Baseline; n=215	86.0 seconds Interval 63.7 to 128.9	—	—
Change From Baseline in the Timed 100-meter Walk Test (T100T) Change from Baseline at Week 24; n=207	-1.2 seconds Interval -11.6 to 1.9	—	—
Change From Baseline in the Timed 100-meter Walk Test (T100T) Change from Baseline at Week 48; n=199	-1.6 seconds Interval -13.7 to 2.8	—	—

PRIMARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data at given time point.

In the T25FW, the participant is instructed to walk as fast as possible for a distance of 25 feet.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Change From Baseline in the Timed 25-foot Walk Test (T25FW) Baseline; n=215	6.6 seconds Interval 5.2 to 10.2	—	—
Change From Baseline in the Timed 25-foot Walk Test (T25FW) Change from Baseline at Week 24; n=207	-0.1 seconds Interval -0.7 to 0.2	—	—
Change From Baseline in the Timed 25-foot Walk Test (T25FW) Change from Baseline at Week 48; n=199	-0.1 seconds Interval -0.6 to 0.3	—	—

PRIMARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=those participants with observed data at given time point.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Change From Baseline in Maximum Walking Distance (MWD) Change from Baseline at Week 48; n=129	0.0 meters Interval 0.0 to 150.0	—	—
Change From Baseline in Maximum Walking Distance (MWD) Baseline; n=143	350.0 meters Interval 200.0 to 1000.0	—	—
Change From Baseline in Maximum Walking Distance (MWD) Change from Baseline at Week 24; n=136	0.0 meters Interval 0.0 to 170.0	—	—

PRIMARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data at given time point.

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Change From Baseline in Expanded Disability Status Scale (EDSS) Baseline; n=215	4.0 units on a scale Interval 2.5 to 5.0	—	—
Change From Baseline in Expanded Disability Status Scale (EDSS) Change from Baseline at Week 24; n=207	0.0 units on a scale Interval -0.5 to 0.0	—	—
Change From Baseline in Expanded Disability Status Scale (EDSS) Change from Baseline at Week 48; n=199	0.0 units on a scale Interval -0.5 to 0.0	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and MWD (Pearson Correlation Coefficient) Baseline; n=143	-0.7245 Correlation coefficient	—	—
Correlation Between the EDSS and MWD (Pearson Correlation Coefficient) Change from Baseline at Week 24; n=131	-0.6937 Correlation coefficient	—	—
Correlation Between the EDSS and MWD (Pearson Correlation Coefficient) Change from Baseline at week 48; n=124	-0.4188 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and MWD (Spearman Correlation Coefficient) Baseline; n=143	-0.9197 Correlation coefficient	—	—
Correlation Between the EDSS and MWD (Spearman Correlation Coefficient) Change from Baseline at Week 24; n=131	-0.6797 Correlation coefficient	—	—
Correlation Between the EDSS and MWD (Spearman Correlation Coefficient) Change from Baseline at week 48; n=124	-0.5861 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the T100T and T25FW (Pearson Correlation Coefficient) Baseline; n=215	0.9235 Correlation coefficient	—	—
Correlation Between the T100T and T25FW (Pearson Correlation Coefficient) Change from Baseline at Week 24; n=207	0.4752 Correlation coefficient	—	—
Correlation Between the T100T and T25FW (Pearson Correlation Coefficient) Change from Baseline at week 48; n=199	0.4827 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the T100T and T25FW (Spearman Correlation Coefficient) Baseline; n=215	0.8737 Correlation coefficient	—	—
Correlation Between the T100T and T25FW (Spearman Correlation Coefficient) Change from Baseline at Week 24; n=207	0.5558 Correlation coefficient	—	—
Correlation Between the T100T and T25FW (Spearman Correlation Coefficient) Change from Baseline at Week 48; n=199	0.4777 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient) Baseline; n=215	0.5134 Correlation coefficient	—	—
Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient) Change from Baseline at Week 24; n=207	0.1945 Correlation coefficient	—	—
Correlation Between the EDSS and T25FW (Pearson Correlation Coefficient) Change from Baseline at Week 48; n=199	0.1237 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient) Baseline; n=215	0.7574 Correlation coefficient	—	—
Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient) Change from Baseline at Week 24; n=207	0.2623 Correlation coefficient	—	—
Correlation Between the EDSS and T25FW (Spearman Correlation Coefficient) Change from Baseline at Week 48; n=199	0.2661 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Pearson correlation coefficient is a measure of the linear correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and T100T (Pearson Correlation Coefficient) Baseline; n=215	0.5356 Correlation coefficient	—	—
Correlation Between the EDSS and T100T (Pearson Correlation Coefficient) Change from Baseline at Week 24; n=207	0.2176 Correlation coefficient	—	—
Correlation Between the EDSS and T100T (Pearson Correlation Coefficient) Change from Baseline at Week 48; n=199	0.1218 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n=number of participants with data evaluated at given time point.

Spearman correlation coefficient is a non-parametric measure of the correlation (dependence) between 2 variables, giving a value between +1 and -1 inclusive, where 1 is total positive correlation, 0 is no correlation, and -1 is total negative correlation.

Outcome measures

Measure	Natalizumab n=215 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Correlation Between the EDSS and T100T (Spearman Correlation Coefficient) Baseline; n=215	0.7269 Correlation coefficient	—	—
Correlation Between the EDSS and T100T (Spearman Correlation Coefficient) Change from Baseline at Week 24; n=207	0.3778 Correlation coefficient	—	—
Correlation Between the EDSS and T100T (Spearman Correlation Coefficient) Change from Baseline at Week 48; n=199	0.2898 Correlation coefficient	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48

Population: Efficacy Analysis Population (participants who had at least 1 infusion of natalizumab and completed at least 1 on-treatment evaluation); n= number of participants with evaluable data at time point.

To determine how well each of the walking tests, T100T or T25FW, predicts walking limitations, participants were stratified by baseline EDSS scores, and walking tests at Weeks 24 and 48 were analyzed. A 15% or 20% improvement indicates that, when compared with baseline walking speed (meters per second), there is at least 15% or 20% improvement at the corresponding timepoint, e.g. (speed at Week 24 - speed at baseline)/speed at baseline*100% ≥ 15% or 20%. Confirmed (conf) improvement at Week 48 indicates that the participant has at least 15% (or 20%) improvement in walking speed at both Week 24 and Week 48.

Outcome measures

Measure	Natalizumab n=53 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks	Natalizumab: Baseline EDSS 3.0 to 4.0 n=74 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS 3.0 to 4.0	Natalizumab: Baseline EDSS >= 4.5 n=80 Participants natalizumab 300 mg IV every 4 weeks for 48 weeks in participants with a Baseline EDSS \>= 4.5
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 15% Improved at Week 24; n=53,74,80	6 participants	11 participants	19 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 20% Improved at Week 48 conf; n=52,74,72	2 participants	4 participants	7 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 15% Improved at Week 48; n=52,74,73	11 participants	20 participants	24 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 20% Improved at Week 24; n=53,74,80	10 participants	10 participants	18 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 20% Improved at Week 48; n=52,74,73	9 participants	17 participants	23 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 15% Improved at Week 48; n=52,74,73	8 participants	12 participants	15 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 15% Improved at Week 48 conf; n=52,74,72	3 participants	6 participants	10 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 20% Improved at Week 24; n=52,74,80	5 participants	8 participants	14 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T25FW: 20% Improved at Week 48; n=52,74,73	6 participants	8 participants	12 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 15% Improved at Week 24; n=53,74,80	11 participants	13 participants	24 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 15% Improved at Week 48 conf; n=52,74,72	7 participants	12 participants	21 participants
Improvement in Timed 25FT Walk Speed and T100T Speed at Week 24 and 48 T100T: 20% Improved at Week 48 conf; n=52,74,72	6 participants	9 participants	16 participants

Adverse Events

Natalizumab

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Natalizumab n=218 participants at risk natalizumab 300 mg IV every 4 weeks for 48 weeks
Infections and infestations Pneumonia	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Infections and infestations Sepsis	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Blood and lymphatic system disorders Leukopenia	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Cardiac disorders Aortic valve stenosis	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
General disorders Sudden death	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Immune system disorders Anaphylactic reaction	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Nervous system disorders Multiple sclerosis relapse	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Renal and urinary disorders Calculus ureteric	0.46% 1/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up

Other adverse events

Measure	Natalizumab n=218 participants at risk natalizumab 300 mg IV every 4 weeks for 48 weeks
Infections and infestations Upper respiratory tract infection	8.3% 18/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up
Nervous system disorders Headache	6.4% 14/218 • Day 1 (Baseline) through Week 48 (± 7 days) plus 4 weeks (± 7 days) follow-up

Additional Information

Biogen Idec Study Medical Director

Biogen Idec

Email: clinicaltrials@biogenidec.com

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