ACTION: Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke

• Sponsor: Biogen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01955707
• Collaborator: (none)
• Enrollment: 161
• Locations: 50
• Arms: 2
• Duration (Months): 14.9
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of the study is to determine whether one 300 mg dose of intravenous (IV) natalizumab reduces change in infarct volume from Baseline to Day 5 on magnetic resonance imaging (MRI) in participants with acute ischemic stroke when given at ≤6 hours or at >6 to ≤9 hours from when they were last known normal (LKN).

The secondary objectives of this study in this study population are as follows: to assess the efficacy of natalizumab on change in infarct volume from Baseline to Day 30; to assess efficacy of natalizumab on change in infarct volume from 24 hours to Day 5 and Day 30; to assess the efficacy of natalizumab on clinical measures of stroke outcome; to assess the safety of natalizumab in participants with acute ischemic stroke.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke	Drug: natalizumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Study to Evaluate the Safety and Efficacy of Intravenous Natalizumab (BG00002) on Reducing Infarct Volume in Acute Ischemic Stroke
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: natalizumab 300 mg single intravenous (IV) injection	Drug: natalizumab; Administered as described in the treatment arm; Other Names: Tysabri BG00002
Placebo Comparator: Placebo A single IV dose of placebo	Drug: Placebo; Matched placebo

Outcome Measures

Primary Outcome Measures

1. Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) [Baseline, Day 5]

   Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 5 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.

Secondary Outcome Measures

1. Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR) [Baseline, 24 hrs]

   Relative growth of infarct volume from Baseline (relative growth = FLAIR at 24 hours divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.

2. Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR) [Baseline, Day 30]

   Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 30 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.

3. Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR) [24 hours, Day 5]

   Relative growth of infarct volume from 24 hours (relative growth = FLAIR at Day 5 divided by FLAIR at 24 hours). Geometric mean calculated as the exponential of the mean log relative growth.

4. Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR) [24 hours, Day 30]

   Relative growth in infarct volume from Baseline (relative growth = FLAIR Day 30 divided by FLAIR at 24 hours ). Geometric mean calculated as the exponential of the mean log relative growth.

5. Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR) [Day 5, Day 30]

   Relative growth of infarct volume from Day 5 (relative growth = FLAIR at Day 30 divided by FLAIR at Day 5). Geometric mean calculated as the exponential of the mean log relative growth.

6. Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90 [Baseline, 24 hours, Day 5, Day 30, Day 90]

   The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Scores for the NIHSS range from 0 to 42, with 0 representing no symptoms and 42 representing death.

7. Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90 [Day 5, Day 30, and Day 90]

   The mRS measures independence, rather than neurologic function, with specific tasks pre- and post-stroke, respectively. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. The distribution of mRS scores was summarized at each timepoint. An excellent outcome on the mRS was defined as a score of 0 or 1, while a good outcome was defined as a score of 0, 1, or 2.

8. Barthel Index at Day 5, Day 30, and Day 90 [Day 5, Day 30, and Day 90]

   The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility, and can be used to determine a baseline level of functioning and to monitor change in activities of daily living over time. The scores for each of the items are summed to create a total score up to a potential of 100, with higher scores representing a greater level of independence.

9. Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Day 90 ± 5 days]

   AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as severe, moderate, or mild, and related or not related to study treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Diagnosis of acute ischemic stroke.

• Score of ≥6 points on the National Institute of Health Stroke Scale (NIHSS) at Screening.

• At least 1 acute infarct with largest diameter of more than 2 cm on Baseline brain diffusion-weighted imaging (DWI).

• Participants who have received reperfusion therapy may be eligible to participate but must meet all eligibility criteria and perform the Baseline study magnetic resonance imaging (MRI) after reperfusion therapy has been completed.

• Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 3 months after their dose of study treatment.

Key Exclusion Criteria:

• Presence of any intracranial hemorrhage (ICH) on head computed tomography (CT) or non-petechial ICH on screening MRI.

• Stroke isolated to the brainstem.

• Presence of coma

• Expected to die OR unable to be evaluated within 5 days.

• Hypotension requiring the use of intravenous (IV) vasopressor support or systolic blood pressure <90 mmHg at the time of randomization.

• Known prior treatment with natalizumab.

• Immunocompromised subjects, as determined by the Investigator.

• History of progressive multifocal leukoencephalopathy (PML).

• Contraindications to MRI, e.g., implanted pacemaker or other contraindicated implanted metal devices, history of or risk for side effects from gadolinium, or claustrophobia that cannot be medically managed.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	San Diego	California	United States
2	Research Site	Gainesville	Florida	United States
3	Research Site	Kansas City	Kansas	United States	66160
4	Research Site	Boston	Massachusetts	United States	02114
5	Research Site	Golden Valley	Minnesota	United States	55422
6	Research Site	St. Louis	Missouri	United States	63110
7	Research Site	Lake Success	New York	United States
8	Research Site	New York	New York	United States	10032
9	Research Site	Durham	North Carolina	United States	27710
10	Research Site	Akron	Ohio	United States
11	Research Site	Dayton	Ohio	United States	45409
12	Research Site	Toledo	Ohio	United States
13	Research Site	Portland	Oregon	United States
14	Research Site	Tualatin	Oregon	United States	97062
15	Research Site	Philadelphia	Pennsylvania	United States	19104
16	Research Site	Nashville	Tennessee	United States
17	Research Site	Dallas	Texas	United States
18	Research Site	Charlottesville	Virginia	United States
19	Research Site	Milwaukee	Wisconsin	United States
20	Research Site	Altenburg		Germany	04600
21	Research Site	Bad Neustadt		Germany	97616
22	Research Site	Berlin		Germany	12203
23	Research Site	Bonn		Germany
24	Research Site	Duesseldorf		Germany	40225
25	Research Site	Erlangen		Germany	91054
26	Research Site	Frankfurt		Germany	60528
27	Research Site	Hannover		Germany
28	Research Site	Heidelberg		Germany	69120
29	Research Site	Idar-Oberstein		Germany	55743
30	Research Site	Leipzig		Germany	04103
31	Research Site	Ludwigshafen		Germany	67063
32	Research Site	Ludwigshafen		Germany
33	Research Site	Mannheim		Germany
34	Research Site	Trier		Germany	54290
35	Research Site	Tübingen		Germany	72076
36	Research Site	Ulm		Germany
37	Research Site	Albacete		Spain	02006
38	Research Site	Badalona		Spain	8916
39	Research Site	Barakaldo		Spain
40	Research Site	Barcelona		Spain	8003
41	Research Site	Barcelona		Spain	8035
42	Research Site	Barcelona		Spain	8036
43	Research Site	Girona		Spain	17007
44	Research Site	Madrid		Spain	28034
45	Research Site	Pamplona		Spain	31008
46	Research Site	Santiago de Compostela		Spain	15706
47	Research Site	Sevilla		Spain	41009
48	Research Site	Sevilla		Spain	41013
49	Research Site	Valencia		Spain
50	Research Site	Valladolid		Spain	47005

Sponsors and Collaborators

• Biogen

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT01955707
• Other Study ID Numbers: 101SK201; EUDRA CT NO: 2013-001514-15
• First Posted: Oct 7, 2013
• Last Update Posted: Jul 1, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Natalizumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single intravenous (IV) injection of placebo	300 mg single IV injection of natalizumab
Period Title: Overall Study
STARTED	82	79
Withdrew Prior to Dosing	0	1
Dosed	82	78
Received Total Volume of Study Drug	82	77
COMPLETED	62	57
NOT COMPLETED	20	22

Baseline Characteristics

Arm/Group Title	Placebo	Natalizumab	Total
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab	Total of all reporting groups
Overall Participants	82	79	161
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.6 (11.83)	70.3 (13.34)	71.0 (12.57)
Age, Customized (participants) [Number]
</= 39 years	2 2.4%	3 3.8%	5 3.1%
40 to 59 years	13 15.9%	11 13.9%	24 14.9%
60 to 79 years	41 50%	45 57%	86 53.4%
>/= 80 years	26 31.7%	20 25.3%	46 28.6%
Sex: Female, Male (Count of Participants)
Female	34 41.5%	38 48.1%	72 44.7%
Male	48 58.5%	41 51.9%	89 55.3%

Outcome Measures

1. Primary Outcome

Title	Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
Description	Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 5 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	Baseline, Day 5

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	73	69
Geometric Mean (Inter-Quartile Range) [mL]	2.17	2.37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tissue plasminogen activator (tPA) use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted mean difference (log-scale)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 90%; -0.09 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.779
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 90%; 0.91 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

2. Secondary Outcome

Title	Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
Description	Relative growth of infarct volume from Baseline (relative growth = FLAIR at 24 hours divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	Baseline, 24 hrs

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	74	69
Geometric Mean (Inter-Quartile Range) [mL]	1.73	1.95

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted mean difference (log-scale)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 90%; -0.09 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.797
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 90%; 0.92 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

3. Secondary Outcome

Title	Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
Description	Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 30 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	66	55
Geometric Mean (Inter-Quartile Range) [mL]	1.27	1.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to baseline using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference (log-scale)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 90%; -0.13 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 90%; 0.88 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

4. Secondary Outcome

Title	Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
Description	Relative growth of infarct volume from 24 hours (relative growth = FLAIR at Day 5 divided by FLAIR at 24 hours). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	24 hours, Day 5

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	70	65
Geometric Mean (Inter-Quartile Range) [mL]	1.27	1.25

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to 24 hours using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference (log-scale)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 90%; -0.12 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.487
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 90%; 0.89 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

5. Secondary Outcome

Title	Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
Description	Relative growth in infarct volume from Baseline (relative growth = FLAIR Day 30 divided by FLAIR at 24 hours ). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	24 hours, Day 30

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	62	53
Geometric Mean (Inter-Quartile Range) [mL]	0.75	0.72

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to 24 hours using an autoregressive variance-covariance matrix structure. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, and tPA use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference (log-scale)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 90%; -0.14 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.402
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 90%; 0.87 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

6. Secondary Outcome

Title	Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
Description	Relative growth of infarct volume from Day 5 (relative growth = FLAIR at Day 30 divided by FLAIR at Day 5). Geometric mean calculated as the exponential of the mean log relative growth.
Time Frame	Day 5, Day 30

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment) with assessments at both time points.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	64	54
Geometric Mean (Inter-Quartile Range) [mL]	0.60	0.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Treatment contrasts derived from a repeated measures mixed effects model modeling log relative growth relative to Day 5 using an autoregressive variance-covariance matrix structure. The model adjusts for for treatment, log baseline DWI volume, treatment time window, and tPA use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference (log-scale)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 90%; -0.18 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.394
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	ratio of relative growth
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 90%; 0.84 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted mean (log-scale) back-transformed to the original scale as the estimated ratio of natalizumab to placebo. 90% confidence interval (log-scale) back-transformed to the original scale and reflect the interval around the ratio.

7. Secondary Outcome

Title	Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90
Description	The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Scores for the NIHSS range from 0 to 42, with 0 representing no symptoms and 42 representing death.
Time Frame	Baseline, 24 hours, Day 5, Day 30, Day 90

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment); n=participants with assessments at Baseline and given time point.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	82	77
Change at 24 hours; n=82, 77	-1.5 (3.96)	-1.5 (5.10)
Change at Day 5; n=79, 72	-3.3 (5.31)	-2.1 (6.24)
Change at Day 30; n=73, 62	-5.7 (5.22)	-4.9 (5.73)
Change at Day 90; n=62, 56	-7.3 (3.95)	-6.8 (5.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of NIHSS score and change from Baseline at 24 hours. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.427
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 90%; -2.48 to 1.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of NIHSS score and change from Baseline at Day 5. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.896
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 90%; -0.52 to 3.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of NIHSS score and change from Baseline at Day 30. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.989
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	3.15
	Confidence Interval	(2-Sided) 90%; 0.89 to 5.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of NIHSS score and change from Baseline at Day 90. The repeated measures mixed effects model is modeling absolute change in NIHSS score relative to baseline and using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, baseline NIHSS score and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.915
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	adjusted mean change from baseline
	Estimated Value	1.93
	Confidence Interval	(2-Sided) 90%; -0.38 to 4.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
Description	The mRS measures independence, rather than neurologic function, with specific tasks pre- and post-stroke, respectively. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. The distribution of mRS scores was summarized at each timepoint. An excellent outcome on the mRS was defined as a score of 0 or 1, while a good outcome was defined as a score of 0, 1, or 2.
Time Frame	Day 5, Day 30, and Day 90

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment), using imputed data; n=number of participants with an assessment at given time point.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	82	77
Day 5: Score 0; n=82, 76	0 0%	2 2.5%
Day 5: Score 1; n=82, 76	3 3.7%	2 2.5%
Day 5: Score 2; n=82, 76	10 12.2%	11 13.9%
Day 5: Score 3; n=82, 76	13 15.9%	11 13.9%
Day 5: Score 4; n=82, 76	25 30.5%	16 20.3%
Day 5: Score 5; n=82, 76	29 35.4%	31 39.2%
Day 5: Score 6; n=82, 76	2 2.4%	3 3.8%
Day 30: Score 0; n=81, 72	0 0%	5 6.3%
Day 30: Score 1; n=81, 72	7 8.5%	8 10.1%
Day 30: Score 2; n=81, 72	14 17.1%	8 10.1%
Day 30: Score 3; n=81, 72	17 20.7%	17 21.5%
Day 30: Score 4; n=81, 72	22 26.8%	14 17.7%
Day 30: Score 5; n=81, 72	13 15.9%	11 13.9%
Day 30: Score 6; n=81, 72	8 9.8%	9 11.4%
Day 90: Score 0; n=78, 72	4 4.9%	8 10.1%
Day 90: Score 1; n=78, 72	12 14.6%	10 12.7%
Day 90: Score 2; n=78, 72	12 14.6%	10 12.7%
Day 90: Score 3; n=78, 72	15 18.3%	13 16.5%
Day 90: Score 4; n=78, 72	14 17.1%	11 13.9%
Day 90: Score 5; n=78, 72	8 9.8%	6 7.6%
Day 90: Score 6; n=78, 72	13 15.9%	14 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of distribution of mRS scores at Day 5. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments	One sided p-value based on Van Elteren's test, adjusting for baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Method	Van Elteren's test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 90%; 0.55 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of distribution of mRS scores at Day 30. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments	One-sided p-value based on Van Elteren's test, adjusting for baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Method	Van Elteren's test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 90%; 0.80 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of the distribution of mRS scores at Day 90. Odds ratio from a proportional-odds logistic regression model assuming a common odds ratio across all cut points of the mRS score. Covariates include baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.243
	Comments	One -sided p-value based on Van Elteren's test, adjusting for baseline DWI volume (< median vs >= median), treatment time window, location of stroke abnormality (cortical/subcortical), and tPA use (yes/no).
	Method	Van Elteren's test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 90%; 0.71 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Barthel Index at Day 5, Day 30, and Day 90
Description	The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility, and can be used to determine a baseline level of functioning and to monitor change in activities of daily living over time. The scores for each of the items are summed to create a total score up to a potential of 100, with higher scores representing a greater level of independence.
Time Frame	Day 5, Day 30, and Day 90

Outcome Measure Data

Analysis Population Description

Modified intention to treat (all participants who were randomized and received the entire infusion of study treatment); n=participants with assessment at given time point.

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	82	77
Day 5; n=78, 73	35.0	30.0
Day 30; n=73, 60	70.0	80.0
Day 90; n=61, 55	80.0	95.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of Barthel Index at Day 5. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.455
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 90%; -9.19 to 10.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of Barthel Index at Day 30. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.420
	Comments	one-sided p-value
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 90%; -8.76 to 11.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Natalizumab
	Comments	Analysis of Barthel Index at Day 90/Final Visit. The repeated measures mixed effects model is modeling Barthel Index using an autoregressive variance-covariance matrix. The model adjusts for treatment, time, treatment by time, log baseline DWI volume, treatment time window, tPA use, and location of stroke.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.283
	Comments
	Method	repeated measures mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean
	Estimated Value	3.56
	Confidence Interval	(2-Sided) 90%; -6.64 to 13.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as severe, moderate, or mild, and related or not related to study treatment.
Time Frame	Up to Day 90 ± 5 days

Outcome Measure Data

Analysis Population Description

Safety population (all participants who were randomized and received any portion of the infusion of study treatment).

Arm/Group Title	Placebo	Natalizumab
Arm/Group Description	A single IV injection of placebo	300 mg single IV injection of natalizumab
Measure Participants	82	78
Participants with an event	81 98.8%	77 97.5%
Participants with a moderate or severe event	60 73.2%	53 67.1%
Participants with a severe event	27 32.9%	22 27.8%
Participants with a related event	7 8.5%	6 7.6%
Participants with a serious event	38 46.3%	36 45.6%
Participants discontinuing due to an event	0 0%	0 0%
Participants withdrawing from study due to event	2 2.4%	1 1.3%

Adverse Events

Time Frame	From informed consent (SAE) or initiation of study drug (AE) until Final Visit Day 90 ± 5 days or early termination follow-up.
Arm/Group Title	Placebo		Natalizumab
Arm/Group Description	A single IV injection of placebo		300 mg single IV injection of natalizumab
All Cause Mortality
	Placebo		Natalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Natalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/82 (46.3%)		36/78 (46.2%)
Blood and lymphatic system disorders
Splenic haemorrhage	0/82 (0%)		1/78 (1.3%)
Cardiac disorders
Acute myocardial infarction	1/82 (1.2%)		0/78 (0%)
Atrial fibrillation	0/82 (0%)		1/78 (1.3%)
Cardiac arrest	0/82 (0%)		1/78 (1.3%)
Cardiac failure	2/82 (2.4%)		0/78 (0%)
Cardiac failure chronic	1/82 (1.2%)		0/78 (0%)
Intracardiac thrombus	0/82 (0%)		1/78 (1.3%)
Myocardial infarction	2/82 (2.4%)		0/78 (0%)
Pulseless electrical activity	1/82 (1.2%)		0/78 (0%)
Ventricular tachycardia	0/82 (0%)		1/78 (1.3%)
Endocrine disorders
Toxic nodular goitre	1/82 (1.2%)		0/78 (0%)
General disorders
Death	0/82 (0%)		1/78 (1.3%)
Device dislocation	0/82 (0%)		1/78 (1.3%)
Multi-organ failure	0/82 (0%)		2/78 (2.6%)
Hepatobiliary disorders
Cholecystitis acute	1/82 (1.2%)		0/78 (0%)
Infections and infestations
Diverticulitis	1/82 (1.2%)		0/78 (0%)
Endocarditis	1/82 (1.2%)		0/78 (0%)
Gastroenteritis	0/82 (0%)		1/78 (1.3%)
Influenza	0/82 (0%)		1/78 (1.3%)
Pneumonia	2/82 (2.4%)		3/78 (3.8%)
Respiratory tract infection	1/82 (1.2%)		1/78 (1.3%)
Septic shock	0/82 (0%)		1/78 (1.3%)
Urinary tract infection	2/82 (2.4%)		0/78 (0%)
Urinary tract infection pseudomonal	1/82 (1.2%)		0/78 (0%)
Injury, poisoning and procedural complications
Avulsion fracture	0/82 (0%)		1/78 (1.3%)
Brain herniation	1/82 (1.2%)		1/78 (1.3%)
Fall	1/82 (1.2%)		0/78 (0%)
Femur fracture	2/82 (2.4%)		0/78 (0%)
Hip fracture	0/82 (0%)		1/78 (1.3%)
Metabolism and nutrition disorders
Dehydration	1/82 (1.2%)		0/78 (0%)
Hyponatraemia	1/82 (1.2%)		0/78 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma	0/82 (0%)		1/78 (1.3%)
Glioma	1/82 (1.2%)		0/78 (0%)
Nervous system disorders
Basilar artery thrombosis	1/82 (1.2%)		0/78 (0%)
Brain midline shift	1/82 (1.2%)		1/78 (1.3%)
Brain oedema	2/82 (2.4%)		1/78 (1.3%)
Carotid artery stenosis	1/82 (1.2%)		3/78 (3.8%)
Cerebral infarction	2/82 (2.4%)		4/78 (5.1%)
Cerebral ischaemia	1/82 (1.2%)		1/78 (1.3%)
Cerebrovascular accident	2/82 (2.4%)		2/78 (2.6%)
Convulsion	0/82 (0%)		2/78 (2.6%)
Dementia	0/82 (0%)		1/78 (1.3%)
Dementia alzheimer's type	1/82 (1.2%)		0/78 (0%)
Encephalopathy	0/82 (0%)		1/78 (1.3%)
Epilepsy	0/82 (0%)		1/78 (1.3%)
Generalised non-convulsive epilepsy	0/82 (0%)		1/78 (1.3%)
Haemorrhage intracranial	0/82 (0%)		1/78 (1.3%)
Haemorrhagic transformation stroke	3/82 (3.7%)		4/78 (5.1%)
Headache	1/82 (1.2%)		0/78 (0%)
Intracranial pressure increased	0/82 (0%)		1/78 (1.3%)
Ischaemic stroke	1/82 (1.2%)		1/78 (1.3%)
Nervous system disorder	0/82 (0%)		1/78 (1.3%)
Neurological decompensation	2/82 (2.4%)		1/78 (1.3%)
Partial seizures	1/82 (1.2%)		0/78 (0%)
Stroke in evolution	0/82 (0%)		2/78 (2.6%)
Subdural hygroma	1/82 (1.2%)		0/78 (0%)
Vocal cord paralysis	1/82 (1.2%)		0/78 (0%)
Psychiatric disorders
Aggression	1/82 (1.2%)		0/78 (0%)
Delirium	2/82 (2.4%)		0/78 (0%)
Renal and urinary disorders
Renal failure	1/82 (1.2%)		0/78 (0%)
Renal failure chronic	1/82 (1.2%)		0/78 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/82 (1.2%)		1/78 (1.3%)
Pneumonia aspiration	1/82 (1.2%)		1/78 (1.3%)
Respiratory distress	1/82 (1.2%)		0/78 (0%)
Respiratory failure	0/82 (0%)		2/78 (2.6%)
Surgical and medical procedures
Endarterectomy	1/82 (1.2%)		0/78 (0%)
Vascular disorders
Peripheral embolism	1/82 (1.2%)		0/78 (0%)
Peripheral ischaemia	1/82 (1.2%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Natalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/82 (91.5%)		68/78 (87.2%)
Blood and lymphatic system disorders
Anaemia	4/82 (4.9%)		8/78 (10.3%)
Cardiac disorders
Atrial fibrillation	10/82 (12.2%)		7/78 (9%)
Bradycardia	5/82 (6.1%)		1/78 (1.3%)
Tachycardia	5/82 (6.1%)		3/78 (3.8%)
Gastrointestinal disorders
Constipation	23/82 (28%)		24/78 (30.8%)
Nausea	11/82 (13.4%)		9/78 (11.5%)
Vomiting	15/82 (18.3%)		5/78 (6.4%)
General disorders
Pain	6/82 (7.3%)		9/78 (11.5%)
Pyrexia	26/82 (31.7%)		32/78 (41%)
Infections and infestations
Pneumonia	6/82 (7.3%)		10/78 (12.8%)
Respiratory tract infection	9/82 (11%)		4/78 (5.1%)
Urinary tract infection	13/82 (15.9%)		19/78 (24.4%)
Injury, poisoning and procedural complications
Fall	4/82 (4.9%)		8/78 (10.3%)
Investigations
Alanine aminotransferase increased	1/82 (1.2%)		5/78 (6.4%)
Aspartate aminotransferase increased	2/82 (2.4%)		4/78 (5.1%)
Gamma-glutamyltransferase increased	5/82 (6.1%)		4/78 (5.1%)
Metabolism and nutrition disorders
Diabetes mellitus	2/82 (2.4%)		4/78 (5.1%)
Hypercholesterolaemia	3/82 (3.7%)		6/78 (7.7%)
Hyperglycaemia	3/82 (3.7%)		9/78 (11.5%)
Hypokalaemia	10/82 (12.2%)		10/78 (12.8%)
Hyponatraemia	5/82 (6.1%)		3/78 (3.8%)
Musculoskeletal and connective tissue disorders
Back pain	6/82 (7.3%)		4/78 (5.1%)
Pain in extremity	4/82 (4.9%)		4/78 (5.1%)
Nervous system disorders
Brain oedema	3/82 (3.7%)		6/78 (7.7%)
Cerebral haemorrhage	0/82 (0%)		4/78 (5.1%)
Haemorrhagic transformation stroke	21/82 (25.6%)		18/78 (23.1%)
Headache	19/82 (23.2%)		13/78 (16.7%)
Neurological decompensation	2/82 (2.4%)		4/78 (5.1%)
Somnolence	3/82 (3.7%)		4/78 (5.1%)
Psychiatric disorders
Agitation	3/82 (3.7%)		11/78 (14.1%)
Anxiety	1/82 (1.2%)		6/78 (7.7%)
Depression	13/82 (15.9%)		5/78 (6.4%)
Insomnia	13/82 (15.9%)		7/78 (9%)
Post stroke depression	2/82 (2.4%)		4/78 (5.1%)
Sleep disorder	7/82 (8.5%)		8/78 (10.3%)
Renal and urinary disorders
Urinary retention	6/82 (7.3%)		5/78 (6.4%)
Vascular disorders
Hypertension	10/82 (12.2%)		15/78 (19.2%)
Hypotension	12/82 (14.6%)		2/78 (2.6%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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.