Adults 18 to 58, any sex, with Secondary Progressive Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Part 1: Percentage of Participants With Confirmed Progression of Disability in One or More of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)Primary· Up to 96 weeks (2 years)
Confirmed disability progression, defined as ≥1 of the following criteria (confirmed at a second visit ≥6 months later and at Week 96):
* Confirmed progression in EDSS (EDSS score increased from baseline \[BL\] by ≥1 point if BL EDSS ≤5.5 or by ≥0.5 points if BL EDSS ≥6);
* Confirmed progression in T25FW (T25FW increased by ≥20% of the BL walk);
* Confirmed progression in 9HPT (9HPT increased by ≥20% of the time taken at BL on either hand and confirmed on the same hand).
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T2
Confirmed on ≥1 of EDSS, T25FW, or 9HPT at 2 years
Group
Value
95% CI
Placebo
48
43.1 – 52.4
Natalizumab 300 mg
44
39.8 – 49.1
Confirmed on EDSS at 2 years
Group
Value
95% CI
Placebo
15
11.7 – 18.3
Natalizumab 300 mg
16
12.3 – 19.1
Confirmed on T25FW at 2 years
Group
Value
95% CI
Placebo
35
30.8 – 39.7
Natalizumab 300 mg
35
30.4 – 39.3
Confirmed on 9HPT (either hand) at 2 years
Group
Value
95% CI
Placebo
23
19.3 – 27.1
Natalizumab 300 mg
15
11.3 – 17.9
Confirmed on 9HPT (dominant hand) at 2 years
Group
Value
95% CI
Placebo
13
10.2 – 16.5
Natalizumab 300 mg
10
7.2 – 12.8
Confirmed on 9HPT (non-dominant hand) at 2 years
Group
Value
95% CI
Placebo
16
12.5 – 19.2
Natalizumab 300 mg
10
7.2 – 12.8
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)Primary· 218 weeks
AE: any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the participant at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE may have also been any other medically important event in the opinion of the Investigator.
Any event
Group
Value
95% CI
Placebo
250
Natalizumab 300 mg
245
Moderate or severe event
Group
Value
95% CI
Placebo
157
Natalizumab 300 mg
158
Severe event
Group
Value
95% CI
Placebo
28
Natalizumab 300 mg
27
Related event
Group
Value
95% CI
Placebo
63
Natalizumab 300 mg
56
Serious event
Group
Value
95% CI
Placebo
24
Natalizumab 300 mg
39
Discontinuation of treatment due to event
Group
Value
95% CI
Placebo
12
Natalizumab 300 mg
5
Withdrawal from study due to an event
Group
Value
95% CI
Placebo
11
Natalizumab 300 mg
3
Part 1: Percentage of Participants With a T25FW ResponseSecondary· Up to 96 weeks
T25FW response is defined as any improvement from the best pre-dose T25FW in at least 75% of the scheduled on-treatment visits through Week 96. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately administered again by having the patient walk back
Group
Value
95% CI
Placebo
17
12.7 – 20.3
Natalizumab 300 mg
19
14.6 – 22.4
Part 1: Change From Baseline in the 12-Item MS Walking Scale (MSWS-12)Secondary· Baseline and Week 96
MSWS-12 is a participant self-assessment of the walking limitations due to MS during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where higher scores indicate greater impact on walking. A negative number on change from BL value indicates an improvement in MSWS-12.
Group
Value
95% CI
Placebo
4.04
± 21.061
Natalizumab 300 mg
2.70
± 22.110
Part 1: Change From Baseline in Manual Ability Score Based on the ABILHAND QuestionnaireSecondary· Baseline and Week 96
The ABILHAND Questionnaire measures the participant's perceived difficulty in performing everyday manual activities in the last 3 months. The participant completes a 56-item questionnaire by estimating their own difficulty or ease in performing each of 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability. A positive number on change from baseline value indicates an improvement in ABILHAND.
Group
Value
95% CI
Placebo
-3.45
± 14.739
Natalizumab 300 mg
-2.44
± 13.023
Part 1: Change From Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) ScoreSecondary· Baseline and Week 96
The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health. A negative number on change from baseline value indicates an improvement in MSIS-29.
Group
Value
95% CI
Placebo
3.34
± 20.947
Natalizumab 300 mg
0.61
± 19.885
Part 1: Percentage Change From Week 24 in Whole Brain Volume at Week 96Secondary· Week 24 and Week 96
Whole brain volume as measured by MRI.
Group
Value
95% CI
Placebo
-0.72
± 0.656
Natalizumab 300 mg
-0.66
± 0.596
Part 1: Percentage of Participants Defined as Confirmed Progressors on EDSS Functional System ScoresSecondary· Up to 96 weeks
The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. Participants with confirmed progression of disability in EDSS physical functional system scores will be defined as those who met one of the following criteria:
* an increase of ≥ 1 point from baseline system score of ≥ 1 or an increase of ≥ 2 points from baseline system score of 0 in at least 2 physical functional systems, or
* an increase of ≥ 2 points from baseline system sc
Group
Value
95% CI
Placebo
29
25.2 – 33.7
Natalizumab 300 mg
25
20.6 – 28.6
Part 2: Percentage of Participants With Disability Worsening at 156 WeeksSecondary· Week 156
Percentage of participants with disability worsening at each scheduled efficacy visit in Part 2, defined as one or more of the following: • ≥ 20% worsening from Part 1 baseline in T25FW; • ≥ 20% worsening from Part 1 baseline in 9HPT; • Worsening from Part 1 baseline in EDSS (≥ 1 point increase if Part 1 baseline EDSS ≤ 5.5 or ≥ 0.5 point increase if Part 1 baseline EDSS \> 5.5). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed
Confirmed on ≥1 of EDSS, T25FW, 9HPT at 156 weeks
Group
Value
95% CI
Placebo
61
55.2 – 66.7
Natalizumab 300 mg
52
45.8 – 57.3
Confirmed on EDSS at 156 weeks
Group
Value
95% CI
Placebo
23
18.3 – 28.4
Natalizumab 300 mg
18
13.8 – 22.6
Confirmed on T25FW at 156 weeks
Group
Value
95% CI
Placebo
46
40.1 – 51.9
Natalizumab 300 mg
41
35.2 – 46.5
Confirmed on 9HPT (either hand) at 156 weeks
Group
Value
95% CI
Placebo
28
23.1 – 33.8
Natalizumab 300 mg
19
14.4 – 23.4
Confirmed on 9HPT (dominant hand) at 156 weeks
Group
Value
95% CI
Placebo
18
13.0 – 22.0
Natalizumab 300 mg
12
8.0 – 15.4
Confirmed on 9HPT (non-dominant hand) at 156 weeks
Group
Value
95% CI
Placebo
18
13.0 – 22.0
Natalizumab 300 mg
13
9.2 – 16.9
Part 2: Absolute Change From Baseline (Part 1) in T25FWSecondary· Baseline (Part 1) and Weeks 156, 204
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Lower scores on time taken to reach 25 foot mark reflect a better outcome. Values are presented for the overall group, as
Overall: Change from BL to Week 156; n=255, 264
Group
Value
95% CI
Placebo
12.80
± 35.111
Natalizumab 300 mg
7.78
± 21.251
Overall: Change from BL to Week 204; n=39, 38
Group
Value
95% CI
Placebo
25.01
± 56.582
Natalizumab 300 mg
9.01
± 22.507
CP Group: Change from BL to Week 156; n=156, 135
Group
Value
95% CI
Placebo
21.67
± 42.510
Natalizumab 300 mg
16.26
± 26.943
CP Group: Change from BL to Week 204; n=25, 18
Group
Value
95% CI
Placebo
40.06
± 66.275
Natalizumab 300 mg
20.89
± 28.200
NP Group: Change from BL to Week 156; n=99, 129
Group
Value
95% CI
Placebo
-1.17
± 3.804
Natalizumab 300 mg
-1.09
± 3.593
NP Group: Change from BL to Week 204; n=14, 20
Group
Value
95% CI
Placebo
-1.88
± 5.917
Natalizumab 300 mg
-1.67
± 4.613
Part 2: Percentage Change From Baseline (Part 1) in T25FWSecondary· Baseline (Part 1) and Weeks 156, 204
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The participant is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task is immediately repeated; the score for the T25FW is the average of the two completed trials. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above)
Overall: Change from BL at Week 156; n=255, 264
Group
Value
95% CI
Placebo
75.52
± 166.191
Natalizumab 300 mg
55.91
± 130.286
Overall: Change from BL at Week 204; n=39, 38
Group
Value
95% CI
Placebo
130.72
± 272.117
Natalizumab 300 mg
71.09
± 177.668
CP Group: Change from BL at Week 156; n=156, 135
Group
Value
95% CI
Placebo
127.05
± 195.138
Natalizumab 300 mg
113.51
± 160.857
CP Group: Change from BL at Week 204; n=25, 18
Group
Value
95% CI
Placebo
206.78
± 316.344
Natalizumab 300 mg
158.91
± 228.458
NP Group: Change from BL at Week 156; n=99, 129
Group
Value
95% CI
Placebo
-5.68
± 21.708
Natalizumab 300 mg
-4.37
± 25.050
NP Group: Change from BL at Week 204; n=14, 20
Group
Value
95% CI
Placebo
-5.09
± 26.591
Natalizumab 300 mg
-7.94
± 29.856
Part 2: Absolute Change From Baseline (Part 1) in 9HPT (Dominant Hand)Secondary· Baseline (Part 1) and Weeks 156, 204
The 9HPT is a brief, standardized, quantitative test of upper extremity function. The participant picks up 9 pegs puts them in a block containing nine empty holes, and, once they are in the holes, removes them again as quickly as possible one at a time. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged. Values are presented for the overall group, as well as the CP (defined in the primary outcome measure description above) and NP s
Overall: Change from BL to Week 156; n= 257, 271
Group
Value
95% CI
Placebo
5.22
± 27.728
Natalizumab 300 mg
2.12
± 16.719
Overall: Change from BL to Week 204; n=39, 38
Group
Value
95% CI
Placebo
0.56
± 7.923
Natalizumab 300 mg
2.65
± 16.001
CP Group: Change from BL to Week 156; n=158, 138
Group
Value
95% CI
Placebo
10.12
± 33.675
Natalizumab 300 mg
5.01
± 20.625
CP Group: Change from BL to Week 204; n=24, 19
Group
Value
95% CI
Placebo
2.36
± 9.187
Natalizumab 300 mg
6.03
± 21.994
NP Group: Change from BL to Week 156; n=99, 133
Group
Value
95% CI
Placebo
-2.60
± 9.543
Natalizumab 300 mg
-0.89
± 10.602
NP Group: Change from BL to Week 204; n=15, 19
Group
Value
95% CI
Placebo
-2.32
± 4.153
Natalizumab 300 mg
-0.73
± 4.292
Adverse events — posted to ClinicalTrials.gov
Time frame: Adverse events are captured through the last study visit; participants were followed through Week 228, or 24 weeks following last dose of study treatment, or premature withdrawal..
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), participants will have the option of enrolling in a 2-year open-label extension (Part 2).
Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS).
The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores.
Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS.
The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or participant-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT05627271 — The 'Wearing Off' Effect of DMT
· completed
NCT02730455 — Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
· Phase 2
· completed
NCT02677077 — Clinical Disease Activity With Long Term Natalizumab Treatment
· completed
NCT02386566 — Observational Study to Assess the Correlation of EDSS With Quality of Life in MS Participants Treated With Natalizumab
· completed
NCT02142192 — Natalizumab Subcutaneous Immunogenicity and Safety Study
· Phase 2
· terminated
Other recruiting trials for Secondary Progressive Multiple Sclerosis
Currently open trials in the same condition.
NCT06372145 — A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.
· Phase 3
· active not recruiting
NCT05327322 — Functional Outcomes From Diets in Multiple Sclerosis
· NA
· active not recruiting
NCT04688788 — Non-inferiority Study of Ocrelizumab and Rituximab in Active Multiple Sclerosis
· Phase 3
· active not recruiting
NCT03783416 — SIZOMUS Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis
· Phase 1
· recruiting
Other Biogen trials
Trials by the same sponsor.
NCT07483632 — A Study to Learn About the Safety of Diroximel Fumarate (DRF) and Dimethyl Fumarate (DMF) and Their Effects on Relapses
· Phase 3
· not yet recruiting
NCT06628687 — A Study to Learn How BIIB141 (Omaveloxolone) Affects the Health of Participants With Friedrich's Ataxia Who Took it Duri
· recruiting
NCT07444450 — A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy
· Phase 3
· not yet recruiting
NCT07444489 — A Study to Learn More About the Long-Term Safety and Effects of Felzartamab Infusions in Adults With Kidney Transplants
· Phase 3
· not yet recruiting
NCT07444476 — A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety in Participants Aged 15 to 60 Years Wit
· Phase 3
· not yet recruiting
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Biogen
Last refreshed: 11 September 2017
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01416181.