Relapsing-Remitting Multiple Sclerosis
Conditions
Brief summary
This open-label extension study will evaluate the long-term safety of glatiramer acetate and its effect on the neurologic course of participants with relapsing-remitting multiple sclerosis (RRMS). Participants have scheduled visits every 3 months to assess glatiramer acetate safety and their Multiple Sclerosis (MS) status.
Interventions
DRUGGlatiramer acetate
Glatiramer acetate will be administered as per the dose and schedule specified in the respective arms.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have participated (been randomized) in the Copaxone double-blind placebo-controlled study 01-9001 and/or the double-placebo-controlled extension study 01-9001E. * Participants could be male or female. Women of childbearing potential must have practiced an acceptable method of birth control. * Participants must have completed the scheduled termination visit for Amendment 12 (Month 264). * Participants must have signed an approved informed consent form (ICF) prior to continuing in the study extension or at the first visit in the extension (Month 264 which corresponds to the termination visit of Amendment 12). * Participants must have been psychologically and physically stable to participate in the trial as judged by the investigator. * All participants enrolled in this extension study were required to have the following study-specific baseline characteristics prior to entry to Study 01-9001: a diagnosis of RRMS as defined by Poser et al 1983, at least 2 clearly identified relapses and remissions in the 2-year period prior to study entry, ambulatory with a Kurtzke EDSS score of 0 to 5.0 inclusive, and a stable neurologic state for at least 30 days prior to study entry.
Exclusion criteria
* Pregnancy or lactation. * Medical or psychiatric conditions that affect the participant's ability to give informed consent or complete the study. * Inability to self-administer subcutaneous medication or lack of another responsible individual to administer the study preparation daily. * Use of approved MS therapies including interferons, experimental MS therapies, or previous immunosuppressive therapy with cytotoxic chemotherapy (azathioprine, cyclophosphamide, or cyclosporine).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Baseline up to Month 288 | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Any AEs included both serious and non-serious AEs. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in Reported AE section. |
| Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288 | Baseline, Month 288 | The EDSS uses an ordinal scale to assess neurologic impairment in Multiple Sclerosis based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral) and an ambulation score were combined to determine the total EDSS score, ranging from 0 (normal) to 10 (death due to Multiple Sclerosis). |
Countries
United States
Participant flow
Recruitment details
Participants who participated in both or either Studies 01-9001 (double-blind \[DB\] placebo-controlled study) and 01-9001E (DB extension study) were eligible to enter into this open-label extension study. Note that the 01-9001 and 01-9001E studies predate NCT assignments.
Pre-assignment details
A total of 209 participants were screened; 208 participants met entry criteria and were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Glatiramer Acetate: Delayed Start Participants who were originally randomized to the placebo group in the 01-9001 and/or the 01-9001E studies received glatiramer acetate 20 mg SC injection daily at the start of this study. After 18 July 2014 (protocol amendment 12), participants were offered the opportunity to continue treatment with glatiramer acetate 20 mg daily or switch to glatiramer acetate 40 mg TIW. The treatment continued for up to 288 months. | 107 |
| Glatiramer Acetate: Early Start Participants who were originally randomized to the glatiramer acetate 20 mg group in the 01-9001 and/or the 01-9001E studies continued to receive glatiramer acetate 20 mg SC injection daily at the start of this study. After 18 July 2014 (protocol amendment 12), participants were offered the opportunity to continue treatment with glatiramer acetate 20 mg daily or switch to glatiramer acetate 40 mg TIW. The treatment continued for up to 288 months. | 101 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Death | 4 | 1 |
| Overall Study | Lost to Follow-up | 9 | 7 |
| Overall Study | Other than specified | 11 | 16 |
| Overall Study | Withdrawal by Subject | 45 | 48 |
Baseline characteristics
| Characteristic | Glatiramer Acetate: Delayed Start | Glatiramer Acetate: Early Start | Total |
|---|---|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 6.57 | 37.2 years STANDARD_DEVIATION 5.79 | 37.1 years STANDARD_DEVIATION 6.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 105 Participants | 101 Participants | 206 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Missing | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 101 Participants | 97 Participants | 198 Participants |
| Sex: Female, Male Female | 82 Participants | 72 Participants | 154 Participants |
| Sex: Female, Male Male | 25 Participants | 29 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 107 | 1 / 101 |
| other Total, other adverse events | 107 / 107 | 100 / 101 |
| serious Total, serious adverse events | 44 / 107 | 38 / 101 |
Outcome results
Primary
Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288
The EDSS uses an ordinal scale to assess neurologic impairment in Multiple Sclerosis based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral) and an ambulation score were combined to determine the total EDSS score, ranging from 0 (normal) to 10 (death due to Multiple Sclerosis).
Time frame: Baseline, Month 288
Population: 01-9004 included participants originally randomized to placebo in 01-9001 and/or 01-9001E studies and switched to glatiramer acetate 20 mg at the start of the 01-9004 study; and participants originally randomized to the glatiramer acetate 20 mg group in 01-9001 and/or 01-9001E studies who continued on this dose in the 01-9004 study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glatiramer Acetate: Delayed Start | Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288 | Baseline | 2.34 units on a scale | Standard Deviation 1.599 |
| Glatiramer Acetate: Delayed Start | Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288 | Change at Month 288 | 1.64 units on a scale | Standard Deviation 1.962 |
| Glatiramer Acetate: Early Start | Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288 | Baseline | 2.23 units on a scale | Standard Deviation 1.406 |
| Glatiramer Acetate: Early Start | Change From Baseline in Kurtzke Expanded Disability Status Scale (EDSS) Score at Month 288 | Change at Month 288 | 1.06 units on a scale | Standard Deviation 1.896 |
Primary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Any AEs included both serious and non-serious AEs. A summary of other non-serious AEs and all serious AEs, regardless of causality, is located in Reported AE section.
Time frame: Baseline up to Month 288
Population: 01-9004 included participants originally randomized to placebo in 01-9001 and/or 01-9001E studies and switched to glatiramer acetate 20 mg at the start of the 01-9004 study; and participants originally randomized to the glatiramer acetate 20 mg group in 01-9001 and/or 01-9001E studies who continued on this dose in the 01-9004 study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glatiramer Acetate: Delayed Start | Number of Participants With Adverse Events (AEs) | Any AEs | 107 participants |
| Glatiramer Acetate: Delayed Start | Number of Participants With Adverse Events (AEs) | Serious AEs | 44 participants |
| Glatiramer Acetate: Early Start | Number of Participants With Adverse Events (AEs) | Any AEs | 100 participants |
| Glatiramer Acetate: Early Start | Number of Participants With Adverse Events (AEs) | Serious AEs | 38 participants |