Trial Outcomes & Findings for Treatment Interruption of Natalizumab (NCT NCT01071083)

Last Updated: 2013-09-19

Results Overview

Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of \>0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of \>0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was \>5.5

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

175 participants

Primary outcome timeframe

28 Weeks

Results posted on

2013-09-19

Participant Flow

Date of first treatment: 31 March 2010. Date of study completion: 02 November 2011.

175 subjects were enrolled, all 175 were randomized.

Participant milestones

Participant milestones
Measure	Intravenous Placebo placebo matching natalizumab, intravenous every 4 weeks	Natalizumab 300 mg intravenous every 4 weeks	Interferon β-1a 30 ug intramuscular once per week	Glatiramer Acetate 20 mg subcutaneous once daily	Methylprednisolone 1000 mg intravenous every 4 weeks
Overall Study STARTED	42	45	17	17	54
Overall Study COMPLETED	35	43	12	15	46
Overall Study NOT COMPLETED	7	2	5	2	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Intravenous Placebo placebo matching natalizumab, intravenous every 4 weeks	Natalizumab 300 mg intravenous every 4 weeks	Interferon β-1a 30 ug intramuscular once per week	Glatiramer Acetate 20 mg subcutaneous once daily	Methylprednisolone 1000 mg intravenous every 4 weeks
Overall Study Adverse Event	1	0	1	0	1
Overall Study Withdrawal by Subject	3	0	2	0	3
Overall Study Physician Decision	1	0	0	1	1
Overall Study Early Rescue	1	0	0	0	1
Overall Study Subject Moved	0	1	0	0	0
Overall Study Images Not Usable (Motion)	0	1	0	0	0
Overall Study Did Not Meet Eligibility Criteria	0	0	1	1	1
Overall Study Did Not Want Per Protocol Treatment	0	0	1	0	1
Overall Study Subject Refused to Continue	1	0	0	0	0

Baseline Characteristics

Treatment Interruption of Natalizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Natalizumab n=45 Participants 300 mg intravenous every 4 weeks	Intravenous Placebo n=42 Participants placebo matching natalizumab, intravenous every 4 weeks	Interferon β-1a n=17 Participants 30 ug intramuscular once per week	Glatiramer Acetate n=17 Participants 20 mg subcutaneous once daily	Methylprednisolone n=54 Participants 1000 mg intravenous every 4 weeks	Total n=175 Participants Total of all reporting groups
Age Continuous	41.2 Years STANDARD_DEVIATION 9.70 • n=5 Participants	40.0 Years STANDARD_DEVIATION 10.36 • n=7 Participants	45.1 Years STANDARD_DEVIATION 9.92 • n=5 Participants	44.1 Years STANDARD_DEVIATION 7.85 • n=4 Participants	40.1 Years STANDARD_DEVIATION 9.96 • n=21 Participants	41.2 Years STANDARD_DEVIATION 9.85 • n=10 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	31 Participants n=7 Participants	14 Participants n=5 Participants	14 Participants n=4 Participants	39 Participants n=21 Participants	135 Participants n=10 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants	40 Participants n=10 Participants

PRIMARY outcome

Timeframe: 28 Weeks

Population: Of the randomized subjects, data from 167 subjects were used in efficacy analyses. Eight subjects were excluded from the analyses: 3 subjects had major protocol deviations and 5 subjects discontinued study participation prior to Week 4 Visit.

Outcome measures

Outcome measures
Measure	Natalizumab n=45 Participants 300 mg intravenous every 4 weeks	Intravenous Placebo n=41 Participants placebo matching natalizumab, intravenous every 4 weeks	Interferon β-1a n=14 Participants 30 ug intramuscular once per week	Glatiramer Acetate n=15 Participants 20 mg subcutaneous once daily	Methylprednisolone n=52 Participants 1000 mg intravenous every 4 weeks
Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.	4.7 Percentage of subjects meeting criteria	60.5 Percentage of subjects meeting criteria	28.6 Percentage of subjects meeting criteria	53.3 Percentage of subjects meeting criteria	54.8 Percentage of subjects meeting criteria

SECONDARY outcome

Timeframe: 28 Weeks

MRI rescue criteria were the presence of 1 new gadolinium-enhancing (Gd+) lesion of \>0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size, according to the central MRI reader.