Trial Outcomes & Findings for Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies (NCT NCT02241785)

Results Overview

The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

47 participants

Primary outcome timeframe

Reset Baseline (Week 8) to Week 56

Results posted on

2017-06-05

Participant Flow

Participant milestones

Participant milestones
Measure	Natalizumab natalizumab 300 mg intravenously (IV) every 4 weeks
Overall Study STARTED	47
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Natalizumab natalizumab 300 mg intravenously (IV) every 4 weeks
Overall Study Sponsor Termination	43
Overall Study Withdrawal by Subject	1
Overall Study Lost to Follow-up	2
Overall Study Adverse Event	1

Baseline Characteristics

Natalizumab as an Efficacy Switch in Participants With Relapsing Multiple Sclerosis After Failure on Other Therapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Natalizumab n=47 Participants natalizumab 300 mg IV every 4 weeks
Age, Continuous	41.9 years STANDARD_DEVIATION 10.43 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Reset Baseline (Week 8) to Week 56

Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.

The proportion of participants with NEDA, defined as follows: no Expanded Disability Status Scale (EDSS) progression (12-week sustained); no relapses; no gadolinium enhancing (Gd+) lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of combined unique active (CUA) lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Day -1) to Reset Baseline (Week 8)

Population: Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.

As measured by magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Natalizumab n=43 Participants natalizumab 300 mg IV every 4 weeks
Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8) Change in T1 Unenhancing Lesion Volume	0.11 cc Standard Deviation 0.65
Change in T1 Unenhancing Lesion Volume and T2 Lesion Volume From Baseline (Day -1) to Reset Baseline (Week 8) Change in T2 Lesion Volume	0.01 cc Standard Deviation 1.76

SECONDARY outcome

Timeframe: from Week 8 (Reset Baseline) to Week 104

Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.

Proportion of participants with NEDA from Week 8 (Reset Baseline) to Week 104 (with no 12-week confirmed EDSS progression determined at Week 116). NEDA was defined as follows: no EDSS progression (12-week sustained); no relapses; no Gd+ lesions; no new or enlarging T2 hyperintense lesions over 48 weeks after resetting the Baseline at Week 8 to remove contribution of CUA lesions that occurred prior to Week 8, when natalizumab was not yet active. The EDSS quantifies disability in 8 functional systems. The final EDSS score is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From 12 months prior to natalizumab infusion and 12 months post-natalizumab infusion

Population: Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.

An MS relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity. 95% confidence interval is based on a Poisson regression model.

Outcome measures

Outcome measures
Measure	Natalizumab n=47 Participants natalizumab 300 mg IV every 4 weeks
Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12 12 months pre-natalizumab infusion	1.553 relapses per subject-year Interval 1.306 to 1.847
Pre- and Post-Natalizumab Infusion Annualized Relapse Rate (ARR) Comparison at Month 12 12 months post-natalizumab infusion	0.159 relapses per subject-year Interval 0.076 to 0.331

SECONDARY outcome

Timeframe: Baseline (Day -1) to Reset Baseline (Week 8)

Population: Intent-to-treat population: participants who received at least 1 infusion of study treatment and had an assessment.

The MSIS-29 is a brief self-administered MS-specific instrument measuring physical (20 items) and mental/psychological (9 items) impact of MS. 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.

Outcome measures

Outcome measures
Measure	Natalizumab n=45 Participants natalizumab 300 mg IV every 4 weeks
Change in MSIS-29 Physical Impact Scores From Baseline (Day -1) to Reset Baseline (Week 8)	-2.53 units on a scale Standard Deviation 12.42

Adverse Events

Natalizumab

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Natalizumab n=47 participants at risk natalizumab 300 mg IV every 4 weeks
Nervous system disorders Syncope	2.1% 1/47 • Number of events 1 • From Screening through end of study. Duration of study treatment was up to 13 months. SAEs only were collected per protocol. Events were not coded by MedDRA.
General disorders Non-cardiac chest pain	2.1% 1/47 • Number of events 1 • From Screening through end of study. Duration of study treatment was up to 13 months. SAEs only were collected per protocol. Events were not coded by MedDRA.

Other adverse events

Adverse event data not reported

Additional Information

Biogen Study Medical Director

Biogen

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