Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
MS
Brief summary
This was a multicenter, randomized, open-label, parallel-group, active-controlled study. Prior to randomization, participants were to have been treated with glatiramer acetate or interferon β-1a (44 μg). Participants were to be randomized to receive natalizumab, interferon β-1a 44 μg, or glatiramer acetate.
Detailed description
The protocol was amended in 15 March 2011 to discontinue participants' enrollment and efficacy assessments, and to offer the opportunity for participants already enrolled to continue receiving study treatment for their planned participation in the study. The study had been active in several countries for approximately 1 year, and enrollment had been significantly slower than expected. Thus, the decision was made by the Sponsor to terminate the study since current and projected future enrollment rates would not have provided valuable information in a reasonable timeframe. All clinical efficacy and magnetic resonance imaging (MRI) procedures were removed from the protocol, and safety assessments were to be managed through standard of care activities.
Interventions
300 mg intravenous injection every 4 weeks
DRUGinterferon beta-1a
44 mcg subcutaneous injection 3 times per week
DRUGglatiramer acetate
20 mg subcutaneous injection once daily
Sponsors
Elan Pharmaceuticals
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Have a diagnosis of relapsing remitting multiple sclerosis (MS) as defined by the revised McDonald Committee criteria (Polman 2005). 2. Must have been treated with a stable regimen of either glatiramer acetate (20 mg per day subcutaneous) or interferon beta-1a (44 mcg 3 times per week subcutaneous) as their principal first therapy for MS for 6 to 18 months prior to randomization. (Note: prior treatment with another MS therapy of ≤ 30 days total duration is not exclusionary \[e.g. titration to 44 mcg is allowed\]). 3. Have had disease activity within 12 months prior to screening while on therapy; disease activity must be observed after a minimum of 6 months on therapy. Qualifying disease activity is defined as: * One or more clinical relapses OR * Two or more new MRI lesions (gadolinium \[Gd+\] and/or T2 hyperintense) For inclusion purposes: (a) a relapse is defined as neurologic signs and/or symptoms documented in the medical record by a neurologist and of sufficient duration to be determined by the Investigator or the Treating Physician as consistent with an MS relapse or (b) MRI activity must be verified by the central reader center. 4. Be naïve to natalizumab. 5. Have a documented Expanded Disability Status Scale (EDSS) score between 0.0 and 5.5, inclusive. Key
Exclusion criteria
1. Have a diagnosis of primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Patients with these conditions may also have superimposed relapses, but are distinguished from relapsing-remitting patients by the lack of clinically stable periods or clinical improvement. 2. Have known intolerance, contraindication to, or history of non-compliance with, the use of glatiramer acetate or interferon beta-1a. 3. Have had an MS exacerbation (relapse) within 30 days prior to randomization AND/OR the patient has not stabilized from a previous relapse, in the opinion of the Investigator, prior to randomization. 4. The patient is considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or due to prior immunosuppressive or immunomodulating treatment. 5. Subjects for whom MRI is contraindicated, i.e., have pacemakers or other contraindicated implanted metal devices, have suffered or are at risk for side effects from gadolinium (Gd), or have claustrophobia that cannot be medically managed. 6. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical trial. 7. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured). 8. Known history of human immunodeficiency virus (HIV). 9. Positive test result for hepatitis C virus (test for hepatitis C virus antibody \[HCVAb\]) or hepatitis B virus (test for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\]). 10. History of transplantation or any anti-rejection therapy. 11. History of progressive multifocal leukoencephalopathy (PML). NOTE: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Serious Adverse Events (SAEs) | up to 108 Weeks | An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also have been any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above. See Adverse Events section below for further details. |
Countries
Australia, Canada, Czechia, Finland, France, Hungary, Italy, Latvia, Poland, Slovenia, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Natalizumab 300 mg intravenous injection every 4 weeks | 36 |
| Interferon Beta-1a 44 mcg subcutaneous injection 3 times per week | 22 |
| Glatiramer Acetate 20 mg subcutaneous injection once daily | 17 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Reason Missing | 5 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 5 | 11 |
| Overall Study | Withdrawn Due to Study Termination | 27 | 13 | 7 |
Baseline characteristics
| Characteristic | Natalizumab | Interferon Beta-1a | Glatiramer Acetate | Total |
|---|---|---|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 9.51 | 39.0 years STANDARD_DEVIATION 10 | 37.6 years STANDARD_DEVIATION 13.16 | 37.1 years STANDARD_DEVIATION 10.52 |
| Sex: Female, Male Female | 30 Participants | 16 Participants | 13 Participants | 59 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 36 | 12 / 22 | 11 / 17 |
| serious Total, serious adverse events | 1 / 36 | 1 / 22 | 0 / 17 |
Outcome results
Primary
Incidence of Treatment-emergent Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the subject at immediate risk of death (a life-threatening event; however, this does not include an event that, had it occurred in a more severe form, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. An SAE may also have been any other medically important event that, in the opinion of the Investigator, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed in the definition above. See Adverse Events section below for further details.
Time frame: up to 108 Weeks
Population: Participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Incidence of Treatment-emergent Serious Adverse Events (SAEs) | 1 participants |
| Interferon Beta-1a | Incidence of Treatment-emergent Serious Adverse Events (SAEs) | 1 participants |
| Glatiramer Acetate | Incidence of Treatment-emergent Serious Adverse Events (SAEs) | 0 participants |