Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparison of Rituximab Induction Therapy Followed by Glatiramer Acetate (GATEWAYII)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01569451
Recruitment Status : Completed
First Posted : April 3, 2012
Results First Posted : June 7, 2018
Last Update Posted : June 8, 2018
Sponsor:
Collaborator:
Rocky Mountain MS Research Group, LLC
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Rituximab
Drug: Glatiramer Acetate
Other: Placebo
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Period Title: Overall Study
Started 26 27
Completed [1] 12 14
Not Completed 14 13
[1]
Represents patients who completed the entire protocol. The analysis of key outcomes included 53
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA) Total
Hide Arm/Group Description

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Total of all reporting groups
Overall Number of Baseline Participants 26 27 53
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 27 participants 53 participants
36.64  (9.15) 36.46  (8.31) 36.55  (8.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
Female
18
  69.2%
19
  70.4%
37
  69.8%
Male
8
  30.8%
8
  29.6%
16
  30.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
Caucasian 21 22 43
Hispanic 1 3 4
Unknown 4 2 6
Type of relapsing MS  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
RRMS/SPMS 24 25 49
CIS 2 2 4
Prior treatment with Tysabri  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
Yes 5 7 12
No 21 20 41
Prior treatment with Tysabri (within 6 months)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
Yes 4 5 9
No 22 22 44
Expanded Disability Status Scale score at baseline   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 26 participants 27 participants 53 participants
2.63  (1.57) 2.80  (1.78) 2.72  (1.67)
[1]
Measure Description: Physicians assess patients' cerebral, optic, brainstem, pyramidal, sensory, cerebellar, and bowel and bladder neurological symptoms. The physician then subjectively rates the patient on the ordinal EDSS scale. The EDSS scale emphasizes ambulatory ability. The EDSS scale ranges in half integer increments from 0.0 to 10.0. Larger numbers mean more disability, with 0.0 being everything normal and 10.0 being death due to MS.
Mean number of GEL at baseline  
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 26 participants 27 participants 53 participants
0.54  (2.16) 1.07  (2.53) 0.81  (2.35)
Number with GEL at baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants 27 participants 53 participants
4 8 12
1.Primary Outcome
Title Number of Disease-free Patients
Hide Description Defined as patients without new lesions on brain MRI using the combined unique lesion approach (CUL), without sustained change in EDSS score over any 3-month period and without relapse. If a clear treatment effect is sustained in the R-GA arm, defined as a ≥ 70% decrease in brain lesions on MRI, using a CUL approach, attributable to MS and ≥ 70% reduction in annual relapse rates, compared to the GA arm, the study will continue under the extension protocol. If induction therapy fails to show superiority, at any point, the study will be stopped.
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Out to the last observation for each patient within 24 months (2 years) of follow up.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
5 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0493
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Time to Treatment Failure
Hide Description Time itself is the outcome. Whenever treatment failure occurs for the first time within the follow up period of 24 months (2 years).
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Time itself is the outcome. Whenever treatment failure occurs for the first time within the follow up period of 24 months (2 years). Exposure time varies by patient. See exposure time outcome (post hoc).
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Median (95% Confidence Interval)
Unit of Measure: months
11.29
(5.25 to 23.39)
23.32 [1] 
(14.64 to NA)
[1]
There was insufficient data to estimate the upper boundary of the confidence interval.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0268
Comments [Not Specified]
Method Peto
Comments [Not Specified]
3.Secondary Outcome
Title Number of Subjects That Fail Treatment
Hide Description [Not Specified]
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At any time within the follow up period of 24 months (2 years) out to the last observation.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
18 10
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0189
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Number of Relapse-free Subjects
Hide Description Change in neurological symptoms in association with EDSS change is defined as relapse.
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Out to the last observation for each patient within 24 months (2 years) of follow up.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
17 21
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3167
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
5.Secondary Outcome
Title Number of Patients Treated for Relapse With Corticosteroid
Hide Description [Not Specified]
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At any time within the follow up period of 24 months (2 years) out to the last observation.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
9 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0940
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
6.Secondary Outcome
Title Number of Subjects Who Experience Multiple Relapses
Hide Description [Not Specified]
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At any time within the follow up period of 24 months (2 years) out to the last observation.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
3 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3507
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Number of Patients That Develop Sustained Accumulation of Disability
Hide Description Sustained accumulation of disability is defined as a 1 point change or more on the Expanded Disability Status Scale (EDSS); sustained for at least three months. Physicians assess patients' cerebral, optic, brainstem, pyramidal, sensory, cerebellar, and bowel and bladder neurological symptoms. The physician then subjectively rates the patient on the ordinal EDSS scale. The EDSS scale emphasizes ambulatory ability. The EDSS scale ranges in half integer increments from 0.0 to 10.0. Larger numbers mean more disability, with 0.0 being everything normal and 10.0 being death due to MS.
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At any observation within the follow up period of 24 months (2 years) out to the last observation.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Number
Unit of Measure: participants
3 4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to 24 Months on the Multiple Sclerosis Functional Composite (MSFC) Z-score
Hide Description The MSFC consists of Timed 25 Foot Walk Tests, 9 Hole Peg Tests, and the Paced Auditory Serial Addition Test (PASAT), administered by clinicians. The subscales are then converted into Z-scores and averaged to create the MSFC Z-score. Larger values denote improvements.
Time Frame Observations were recorded at baseline and 24 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 25 26
Mean (95% Confidence Interval)
Unit of Measure: units on a scale (MSFC Z score)
0.5226
(-0.1840 to 1.2292)
0.2630
(-0.0882 to 0.6141)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments T-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4904
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Subjects Worsening One Point or More on the Patient Determined Disease Steps (PDDS) Questionnaire
Hide Description For PDDS the patient selects an integer 0-8 according to their personal assessment of their degree of ambulatory disability. Larger numbers mean more disability, with 0 being no disability and 8 being bedridden. There is an unclassifiable category as well.
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At any time within the follow up period of 24 months (2 years) out to the last observation.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Measure Type: Count of Participants
Unit of Measure: Participants
6
  23.1%
9
  33.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4073
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
10.Secondary Outcome
Title Change in Mean Score on Performance Scales (Baseline to 24 Months)
Hide Description Performance scales measures patient assessments of disability in mobility (1-6), hand (1-5), vision (1-5), fatigue (1-5), cognitive (1-5), bladder and bowel, sensory (1-5), and spasticity (1-5). The overall measure of performance is the sum of subscales, ranging from 0 to 41. Larger numbers mean more disability, with 0 being no disability and the maximum number being total disability.
Time Frame Baseline through 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
At 24 months (2 years); the end of the study follow up period compared with baseline.
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.1466
(-1.4328 to 1.726)
0.3477
(-1.6109 to 2.3062)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glatiramer Acetate Therapy (GA), Rituximab + Glatiramer Acetate Therapy (R-GA)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8677
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Post-Hoc Outcome
Title Exposure Time
Hide Description Values represent mean duration of treatment.
Time Frame Measured in three month intervals from baseline to end of study.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title (Placebo and) Glatiramer Acetate Rituximab and Glatiramer Acetate (R-GA)
Hide Arm/Group Description:

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Placebo: Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab or placebo (normal saline) on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard Glatiramer Acetate therapy, 20 mg injected subcutaneously daily. There is no placebo arm.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

Overall Number of Participants Analyzed 26 27
Mean (Standard Deviation)
Unit of Measure: years
1.517  (0.766) 1.704  (0.830)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection (Placebo and) Glatiramer Acetate, Rituximab and Glatiramer Acetate (R-GA)
Comments [Not Specified]
Type of Statistical Test Other
Comments Mean difference between treatment groups.
Statistical Test of Hypothesis P-Value 0.3974
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Within 24 months (2 years) of follow up. Exposure time varied by patient.
Adverse Event Reporting Description Out to the last observation for each patient within 24 months (2 years) of follow up. Exposure time varied by patient. See exposure time outcome (post hoc).
 
Arm/Group Title Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Hide Arm/Group Description

Subjects will receive an intravenous (IV) infusion of placebo (normal saline) on study days 1 (baseline visit) and 15 according to the infusion protocol. On study day 28, all subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Glatiramer Acetate: 20 mg injected subcutaneously daily

Subjects will receive an intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15 according to the rituximab infusion protocol. On study day 28, subjects will initiate standard GA therapy, 20 mg injected subcutaneously daily.

Rituximab: intravenous (IV) infusion of 1000 mg of rituximab on study days 1 (baseline visit) and 15

Glatiramer Acetate: 20 mg injected subcutaneously daily

All-Cause Mortality
Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/27 (11.11%)      3/28 (10.71%)    
Blood and lymphatic system disorders     
Pulmonary * 1  1/27 (3.70%)  1 1/28 (3.57%)  1
Gastrointestinal disorders     
GI related * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
General disorders     
Other * 1  2/27 (7.41%)  2 2/28 (7.14%)  3
Immune system disorders     
Relapse related * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
Nervous system disorders     
Neurological Condition * 1  1/27 (3.70%)  1 0/28 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, FDA guidlines
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Glatiramer Acetate Therapy (GA) Rituximab + Glatiramer Acetate Therapy (R-GA)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/27 (100.00%)      27/28 (96.43%)    
Gastrointestinal disorders     
Gastrointestinal Issues * 1  7/27 (25.93%)  7 9/28 (32.14%)  15
General disorders     
Infusion-related reaction * 1  11/27 (40.74%)  13 19/28 (67.86%)  42
Influenza like illness * 1  13/27 (48.15%)  27 17/28 (60.71%)  28
Injection site erythema * 1  2/27 (7.41%)  3 2/28 (7.14%)  2
Fatigue * 1  10/27 (37.04%)  20 11/28 (39.29%)  35
Injection-site reaction * 1  7/27 (25.93%)  11 8/28 (28.57%)  15
Infections and infestations     
URI * 1  9/27 (33.33%)  12 8/28 (28.57%)  13
UTI * 1  6/27 (22.22%)  14 7/28 (25.00%)  13
Bronchitis * 1  2/27 (7.41%)  2 3/28 (10.71%)  3
Musculoskeletal and connective tissue disorders     
Backpain * 1  0/27 (0.00%)  0 2/28 (7.14%)  4
Arthralgia * 1  0/27 (0.00%)  0 2/28 (7.14%)  2
Nervous system disorders     
Headache * 1  10/27 (37.04%)  13 8/28 (28.57%)  11
Psychiatric disorders     
Depression * 1  3/27 (11.11%)  5 5/28 (17.86%)  5
Insomnia * 1  1/27 (3.70%)  1 2/28 (7.14%)  2
Anxiety * 1  5/27 (18.52%)  6 7/28 (25.00%)  10
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, FDA guidlines
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Stefan Sillau
Organization: University of Colorado
Phone: 303-724-8657
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01569451     History of Changes
Other Study ID Numbers: 10-1143
First Submitted: March 30, 2012
First Posted: April 3, 2012
Results First Submitted: October 25, 2016
Results First Posted: June 7, 2018
Last Update Posted: June 8, 2018