Trial Outcomes & Findings for Safety and Tolerability of Glatiramer Acetate (NCT NCT01874145)
NCT ID: NCT01874145
Last Updated: 2016-01-14
Results Overview
Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria). Rate was calculated as # IR events/the total exposure to study drug in years. For cases in which more than 1 IR adverse event started on the same date for the same patient, these were counted as 1 IR adverse event for that patient. Parameter statistics were generated from a Poisson regression model with natural log of treatment duration (years) as an offset variable, and adjusted for baseline EDSS score, treatment group, age, sex, number of relapses in the 2 years prior to screening, in which a contrast comparing treatment groups were constructed. Adjusted mean estimates were adjusted estimates of event rates within treatment group.
COMPLETED
PHASE3
209 participants
Day 1 to Month 4
2016-01-14
Participant Flow
A total of 218 patients with a confirmed and documented RRMS diagnosis were screened for enrollment into this study. Of the 9 patients who were screened but not randomized, 3 were excluded for not meeting the inclusion criteria, 3 were excluded for meeting an exclusion criterion, and 3 were not enrolled for "other" reason.
Participant milestones
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Core Period
STARTED
|
101
|
108
|
|
Core Period
Full Analysis Set
|
100
|
108
|
|
Core Period
COMPLETED
|
98
|
101
|
|
Core Period
NOT COMPLETED
|
3
|
7
|
|
Extension Period
STARTED
|
97
|
101
|
|
Extension Period
Full Analysis Set
|
95
|
101
|
|
Extension Period
COMPLETED
|
91
|
97
|
|
Extension Period
NOT COMPLETED
|
6
|
4
|
Reasons for withdrawal
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Core Period
Non-compliance
|
1
|
0
|
|
Core Period
Protocol Violation
|
1
|
1
|
|
Core Period
Physician Decision
|
1
|
1
|
|
Core Period
Adverse Event
|
0
|
1
|
|
Core Period
Withdrawal by Subject
|
0
|
4
|
|
Extension Period
Adverse Event
|
3
|
2
|
|
Extension Period
Withdrawal by Subject
|
2
|
1
|
|
Extension Period
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Safety and Tolerability of Glatiramer Acetate
Baseline characteristics by cohort
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=101 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=108 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
Total
n=209 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.4 years
STANDARD_DEVIATION 9.34 • n=5 Participants
|
50.9 years
STANDARD_DEVIATION 11.01 • n=7 Participants
|
50.7 years
STANDARD_DEVIATION 10.22 • n=5 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
172 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
99 participants
n=5 Participants
|
107 participants
n=7 Participants
|
206 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
96 participants
n=5 Participants
|
100 participants
n=7 Participants
|
196 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Tobacco user
Current
|
15 participants
n=5 Participants
|
8 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
Tobacco user
Former
|
21 participants
n=5 Participants
|
29 participants
n=7 Participants
|
50 participants
n=5 Participants
|
|
Tobacco user
Never Smoked
|
65 participants
n=5 Participants
|
71 participants
n=7 Participants
|
136 participants
n=5 Participants
|
|
Time to First MS Symptom
|
16.2 years
STANDARD_DEVIATION 10.95 • n=5 Participants
|
15.7 years
STANDARD_DEVIATION 11.10 • n=7 Participants
|
15.9 years
STANDARD_DEVIATION 11.00 • n=5 Participants
|
|
Time from MS Diagnosis
|
12.1 years
STANDARD_DEVIATION 10.04 • n=5 Participants
|
10.8 years
STANDARD_DEVIATION 8.55 • n=7 Participants
|
11.5 years
STANDARD_DEVIATION 9.30 • n=5 Participants
|
|
Number of Relapses in 1 Year Prior to Screening
|
0.2 relapses
STANDARD_DEVIATION 0.41 • n=5 Participants
|
0.2 relapses
STANDARD_DEVIATION 0.47 • n=7 Participants
|
0.2 relapses
STANDARD_DEVIATION 0.44 • n=5 Participants
|
|
Number of Relapses in 2 Years Prior to Screening
|
0.4 relapses
STANDARD_DEVIATION 0.74 • n=5 Participants
|
0.4 relapses
STANDARD_DEVIATION 0.64 • n=7 Participants
|
0.4 relapses
STANDARD_DEVIATION 0.69 • n=5 Participants
|
|
Expanded Disability Status Scale (EDSS)
|
2.4 units on a scale
STANDARD_DEVIATION 1.38 • n=5 Participants
|
2.5 units on a scale
STANDARD_DEVIATION 1.36 • n=7 Participants
|
2.4 units on a scale
STANDARD_DEVIATION 1.37 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Month 4Population: Safety analysis set
Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria). Rate was calculated as # IR events/the total exposure to study drug in years. For cases in which more than 1 IR adverse event started on the same date for the same patient, these were counted as 1 IR adverse event for that patient. Parameter statistics were generated from a Poisson regression model with natural log of treatment duration (years) as an offset variable, and adjusted for baseline EDSS score, treatment group, age, sex, number of relapses in the 2 years prior to screening, in which a contrast comparing treatment groups were constructed. Adjusted mean estimates were adjusted estimates of event rates within treatment group.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=101 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=108 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Adjusted Mean Estimates for Injection-Related Adverse Event Rate Per Year in the Core Period
|
70.403 events per year
Standard Error 11.995
|
35.275 events per year
Standard Error 7.248
|
PRIMARY outcome
Timeframe: Month 5 up to Month 10Population: ITT extension analysis set of participants who had at least one injection-related AE
Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria). Rate was calculated as # IR events/the total exposure to study drug in years. For cases in which more than 1 IR adverse event started on the same date for the same patient, these were counted as 1 IR adverse event for that patient.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=31 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=33 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Injection-Related Adverse Event Rate Per Year in the Extension Period
|
23.1 events per year
|
28.0 events per year
|
PRIMARY outcome
Timeframe: Month 5 up to Month 10Population: ITT extension analysis set of participants who had at least one injection-related AE
Injection-related (IR) adverse events refers to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria).
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=31 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=33 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Injection-Related Adverse Events in the Extension Period
|
772 events
|
979 events
|
SECONDARY outcome
Timeframe: Day 1 to Month 4Population: Safety analysis set
This outcome includes injection-related adverse events referring to all local injection site reactions (ISR). Rate was calculated as # ISR events/the total exposure to study drug in years. For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient. Parameter statistics were generated from a Poisson regression model with natural log of treatment duration (years) as an offset variable, and adjusted for baseline EDSS score, treatment group, age, sex, number of relapses in the 2 years prior to screening, in which a contrast comparing treatment groups were constructed. Adjusted mean estimates were adjusted estimates of event rates within treatment group.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=101 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=108 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Adjusted Mean Estimates for Injection Site Reaction Event Rate Per Year in the Core Period
|
70.392 events per year
Standard Error 12.007
|
35.200 events per year
Standard Error 7.247
|
SECONDARY outcome
Timeframe: Month 0 (baseline), Months 1, 2, 4 (or early termination visit)Population: Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
The physical wellbeing assessment portion of the MSIS-29 is comprised of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. Negative change from baseline scores indicate improvement in physical wellbeing over time. The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline MSIS-29 physical score, treatment group, month, treatment by month interaction.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=85 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=92 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
|
1.536 units on a scale
Standard Error 0.868
|
-0.522 units on a scale
Standard Error 0.832
|
SECONDARY outcome
Timeframe: Month 0 (baseline), Months 1, 2 4 (or early termination visit)Population: Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
The psychological wellbeing assessment portion of the MSIS-29 is comprised of 9 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 9-45. Negative change from baseline scores indicate improvement in psychological wellbeing over time. The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline MSIS-29 psychological score, treatment group, month, treatment by month interaction.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=85 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=92 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
|
0.738 units on a scale
Standard Error 0.533
|
0.016 units on a scale
Standard Error 0.512
|
SECONDARY outcome
Timeframe: Month 0 (baseline), Months 1, 2 4 (or early termination visit)Population: Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on convenience items 4-6, with each question graded on a scale of 1 (extreme dissatisfaction) to 7 (extreme satisfaction). TSQM-9 participant perception of convenience score was calculated as: (\[sum (Item 4 to Item 6) - 3\] divided by 18) \* 100. The full range was -100 to 100, with positive change from baseline indicating improvement. The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline TSQM convenience score, treatment group, month, treatment by month interaction.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=97 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=105 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score in the Core Period
|
1.745 units on a scale
Standard Error 1.457
|
8.751 units on a scale
Standard Error 1.399
|
SECONDARY outcome
Timeframe: Month 0 (baseline), Months 1, 2 4 (or early termination visit)Population: Full analysis set. Some scales/forms were not completed (including partially completed) and therefore not included in this analysis.
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on global satisfaction, items 7-9. TSQM-9 participant perception of satisfaction score was calculated as: (\[sum(Item 7 to Item 9) - 3\] divided by 14) \* 100. The full range was -100 to 100, with positive change from baseline indicating improvement satisfaction with medication. The estimated change from baseline to month 4 adjusted for months 1 and 2 was generated using a mixed model repeated measures analysis adjusted for baseline TSQM convenience score, treatment group, month, treatment by month interaction.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=97 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=105 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score in the Core Period
|
1.555 units on a scale
Standard Error 1.489
|
0.703 units on a scale
Standard Error 1.431
|
SECONDARY outcome
Timeframe: Month 5 up to Month 10Population: ITT extension analysis set of participants who had injection site reaction AEs.
This outcome includes injection-related adverse events referring to all local injection site reactions (ISR). Rate was calculated as # ISR events/the total exposure to study drug in years. For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=31 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=32 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Injection Site Reaction Event Rate Per Year in the Extension Period
|
22.9 events per year
|
28.0 events per year
|
SECONDARY outcome
Timeframe: Month 5 up to Month 10Population: ITT extension analysis set of participants who had injection site reaction AEs.
This outcome includes injection-related adverse events referring to all local injection site reactions (ISR). For cases in which more than 1 ISR adverse event started on the same date for the same patient, these were counted as 1 ISR adverse event for that patient.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=31 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=32 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Injection Site Reaction Events in the Extension Period
|
768 events
|
976 events
|
SECONDARY outcome
Timeframe: Month 4 (baseline for extension period), Month 8, endpoint visitPopulation: Full analysis set Extension Period
The physical wellbeing assessment portion of the MSIS-29 is comprised of 20 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 20-100. Negative change from baseline scores indicate improvement in physical wellbeing. The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=95 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=101 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Month 8 (n=49, 54)
|
-0.6 units on a scale
Standard Deviation 8.09
|
0.8 units on a scale
Standard Deviation 9.53
|
|
Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Endpoint visit (n=95, 101)
|
1.1 units on a scale
Standard Deviation 7.53
|
0.6 units on a scale
Standard Deviation 7.60
|
SECONDARY outcome
Timeframe: Month 4 (baseline for extension period), Month 8, endpoint visitPopulation: Full analysis set Extension Period
The psychological wellbeing assessment portion of the MSIS-29 is comprised of 9 questions in which participants rate the impact of MS on their day-to-day life during the past two weeks from 1=no impact to 5=extreme impact for a total score of 9-45. Negative change from baseline scores indicate improvement in psychological wellbeing. The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=95 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=101 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Month 8 (n=49, 54)
|
1.2 units on a scale
Standard Deviation 4.34
|
0.4 units on a scale
Standard Deviation 5.78
|
|
Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
Endpoint visit (n=95, 101)
|
0.9 units on a scale
Standard Deviation 5.26
|
0.2 units on a scale
Standard Deviation 3.83
|
SECONDARY outcome
Timeframe: Month 4 (baseline for extension period), Month 8, endpoint visitPopulation: Full analysis set Extension Period
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on convenience items 4-6, with each question graded on a scale of 1 (extreme dissatisfaction) to 7 (extreme satisfaction). TSQM-9 participant perception of convenience score was calculated as: (\[sum (Item 4 to Item 6) - 3\] divided by 18) \* 100. The full range was -100 to 100, with positive change from baseline indicating improvement. The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=95 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=101 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score
Month 8 (n=50, 54)
|
4.0 units on a scale
Standard Deviation 18.44
|
-0.2 units on a scale
Standard Deviation 10.41
|
|
Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score
Endpoint visit (n=95, 101)
|
4.3 units on a scale
Standard Deviation 17.41
|
-0.2 units on a scale
Standard Deviation 13.10
|
SECONDARY outcome
Timeframe: Month 4 (baseline for extension period), Month 8, endpoint visitPopulation: Full analysis set Extension Period
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. This outcome focuses on global satisfaction, items 7-9. TSQM-9 participant perception of satisfaction score was calculated as: (\[sum(Item 7 to Item 9) - 3\] divided by 14) \* 100. The full range was -100 to 100, with positive change from baseline indicating improvement satisfaction with medication. The Extension Period endpoint visit was defined as the last observed post-baseline data of the Extension Period.
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=95 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=101 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score
Month 8 (n=50, 54)
|
-0.3 units on a scale
Standard Deviation 14.50
|
-1.2 units on a scale
Standard Deviation 13.58
|
|
Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score
Endpoint visit (n=95, 101)
|
-0.0 units on a scale
Standard Deviation 14.32
|
-1.2 units on a scale
Standard Deviation 11.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Month 4 (core period); Month 5 to 10 (extension period)Population: Safety analysis set
An adverse event was defined in the protocol as any untoward medical occurrence in a patient that developed or worsened in severity during the conduct of the clinical study of a pharmaceutical product and did not necessarily have a causal relationship to the study drug. This outcome summarizes the % of participants who had AEs other than injection related reactions. Injection-related (IR) adverse events referring to all local injection site reactions and/or symptoms or events related to immediate post injection reaction (flushing, chest pain, palpitations, anxiety, dyspnea, throat constriction, and/or urticaria).
Outcome measures
| Measure |
GA 20 mg/mL QD (Core); 40 mg/mL TIW (Extension)
n=101 Participants
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
Participants then switched to 40 mg/mL 3 times a week (TIW) dosing if they chose to continue into the extension period.
|
GA 40 mg/mL TIW (Core and Extension)
n=108 Participants
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
During the Extension period, participants to continue treatment with GA 40 mg/mL TIW until this dose regimen was commercially available for the treatment of RRMS.
|
|---|---|---|
|
Percentage of Participants With Adverse Events Other Than Injection Related Reactions During the Core Period and the Extension Period
Extension Period (n=97, 101)
|
35.1 percentage of participants
|
39.6 percentage of participants
|
|
Percentage of Participants With Adverse Events Other Than Injection Related Reactions During the Core Period and the Extension Period
Core Period (n=101, 108)
|
35.6 percentage of participants
|
47.2 percentage of participants
|
Adverse Events
GA 20 mg/mL QD (Core)
GA 40 mg/mL TIW (Core)
Switchers: 40 mg/mL TIW (Extension)
Non-Switchers: GA 40 mg/mL TIW (Extension)
Serious adverse events
| Measure |
GA 20 mg/mL QD (Core)
n=101 participants at risk
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
|
GA 40 mg/mL TIW (Core)
n=108 participants at risk
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
|
Switchers: 40 mg/mL TIW (Extension)
n=97 participants at risk
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
|
Non-Switchers: GA 40 mg/mL TIW (Extension)
n=101 participants at risk
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Ileitis
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/108 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.99%
1/101 • Number of events 1 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Non-cardiac chest pain
|
0.99%
1/101 • Number of events 1 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/108 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
Infections and infestations
Appendicitis
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.93%
1/108 • Number of events 1 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
Infections and infestations
Respiratory tract infection bacterial
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.93%
1/108 • Number of events 1 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
Nervous system disorders
Multiple sclerosis relapse
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/108 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.99%
1/101 • Number of events 1 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
Other adverse events
| Measure |
GA 20 mg/mL QD (Core)
n=101 participants at risk
Glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period.
|
GA 40 mg/mL TIW (Core)
n=108 participants at risk
Glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week (TIW) for the 4 months of the core period.
|
Switchers: 40 mg/mL TIW (Extension)
n=97 participants at risk
Participants who took glatiramer acetate (GA) 20 mg in 1 mL SC injection administered every day (QD) for the 4 months of the core period. Then switched to 40 mg/mL 3 times a week (TIW) dosing in the extension period.
|
Non-Switchers: GA 40 mg/mL TIW (Extension)
n=101 participants at risk
Participants who took glatiramer acetate (GA) 40 mg in 1 mL SC injection administered three times a week in both the core and extension periods.
|
|---|---|---|---|---|
|
General disorders
Injection site bruising
|
17.8%
18/101 • Number of events 166 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
7.4%
8/108 • Number of events 8 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
4.1%
4/97 • Number of events 10 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
3.0%
3/101 • Number of events 5 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site erythema
|
36.6%
37/101 • Number of events 1331 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
38.0%
41/108 • Number of events 692 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
17.5%
17/97 • Number of events 253 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
20.8%
21/101 • Number of events 436 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site haemorrhage
|
10.9%
11/101 • Number of events 43 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
7.4%
8/108 • Number of events 17 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
3.1%
3/97 • Number of events 5 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
6.9%
7/101 • Number of events 10 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site mass
|
26.7%
27/101 • Number of events 669 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
25.9%
28/108 • Number of events 381 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
12.4%
12/97 • Number of events 122 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
15.8%
16/101 • Number of events 334 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site pain
|
40.6%
41/101 • Number of events 1692 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
38.9%
42/108 • Number of events 803 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
19.6%
19/97 • Number of events 626 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
23.8%
24/101 • Number of events 594 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site pruritus
|
14.9%
15/101 • Number of events 398 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
13.0%
14/108 • Number of events 253 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
6.2%
6/97 • Number of events 85 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
7.9%
8/101 • Number of events 81 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site swelling
|
23.8%
24/101 • Number of events 594 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
17.6%
19/108 • Number of events 170 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
11.3%
11/97 • Number of events 108 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
6.9%
7/101 • Number of events 89 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site urticaria
|
12.9%
13/101 • Number of events 377 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
9.3%
10/108 • Number of events 175 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
4.1%
4/97 • Number of events 77 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
6.9%
7/101 • Number of events 163 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
General disorders
Injection site warmth
|
5.9%
6/101 • Number of events 228 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
3.7%
4/108 • Number of events 24 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
2.1%
2/97 • Number of events 27 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
3.0%
3/101 • Number of events 20 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
Infections and infestations
Sinusitis
|
3.0%
3/101 • Number of events 3 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
5.6%
6/108 • Number of events 6 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/97 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
2.0%
2/101 • Number of events 2 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
|
Nervous system disorders
Dizziness
|
2.0%
2/101 • Number of events 3 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
5.6%
6/108 • Number of events 6 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
5.2%
5/97 • Number of events 5 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
0.00%
0/101 • Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER