Multiple Sclerosis
Conditions
Keywords
natalizumab, Tysabri, Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis
Brief summary
The primary objective of the study was to evaluate the immunogenicity of natalizumab (Tysabri®) produced by a modified manufacturing process (natalizumab high titer; BG00002-E) administered intravenously (IV) to participants with relapsing forms of multiple sclerosis (MS). The secondary objective of this study was to evaluate the safety of natalizumab high titer.
Interventions
BIOLOGICALBG00002-E (natalizumab high titer)
Sponsors
Elan Pharmaceuticals
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of a relapsing form of MS * Must fall within the therapeutic indications stated in the locally approved label for natalizumab * Other protocol-defined inclusion criteria may apply
Exclusion criteria
* Prior treatment with natalizumab * Considered by investigator to be immunocompromised * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status | Assessed every 12 weeks from Week 0 (Baseline) to Week 36 | Negative: no detectable antibody at all post-baseline visits. Persistent positive: antibody positive at 2 or more post-baseline visits at least 42 days apart, or positive at the last post-baseline visit. Transient positive: antibody positive at only 1 post-baseline visit prior to the last visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal. | AE: any sign, symptom, or diagnosis/disease that was unfavorable or unintended, new, or if pre-existing, worsened in a participant administered a study treatment and that did not necessarily have a causal relationship with this treatment. SAE: an event that resulted in death; an event that, in the view of the investigator, placed the participant at immediate risk of death (life-threatening event); an outcome that resulted in a congenital anomaly/birth defect diagnosed in a child of a participant in this study; an event that required or prolonged inpatient hospitalization; an event that resulted in persistent or significant disability/incapacity; any other medically important event that, in the opinion of the investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed above. Events were classified as 'related' or 'not related' to study drug, and categorized as 'mild' moderate' or 'severe' per protocol. |
| Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 36 | Baseline, Week 36 | EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline. |
| Annualized Relapse Rate | Through Week 36 | Annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of years the participant was followed in the study. The annualized relapse rate was based only on those relapses that were determined to meet the definition of relapse per the investigator's clinical judgment. New or recurrent symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Natalizumab High Titer natalizumab high titer 300 mg administered as intravenous (IV) infusion over 60 minutes once every 4 weeks for up to 9 doses | 113 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Noncompliance | 2 |
| Overall Study | Persistent Antibodies per Protocol | 6 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Received Medication From Another Study | 1 |
| Overall Study | Relocated | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Natalizumab High Titer |
|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 8.64 |
| Age, Customized ≥ 18 to < 20 years | 2 participants |
| Age, Customized ≥ 20 to < 30 years | 15 participants |
| Age, Customized ≥ 30 to < 40 years | 43 participants |
| Age, Customized ≥ 40 to < 50 years | 41 participants |
| Age, Customized ≥ 50 to < 56 years | 10 participants |
| Age, Customized ≥ 56 years | 2 participants |
| Expanded Disability Status Score (EDSS) Score | 3.66 scores on a scale STANDARD_DEVIATION 1.817 |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Black | 8 participants |
| Race/Ethnicity, Customized Hispanic | 12 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 91 participants |
| Region of Enrollment United States | 113 participants |
| Sex: Female, Male Female | 91 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 79 / 112 |
| serious Total, serious adverse events | 7 / 112 |
Outcome results
Primary
Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status
Negative: no detectable antibody at all post-baseline visits. Persistent positive: antibody positive at 2 or more post-baseline visits at least 42 days apart, or positive at the last post-baseline visit. Transient positive: antibody positive at only 1 post-baseline visit prior to the last visit.
Time frame: Assessed every 12 weeks from Week 0 (Baseline) to Week 36
Population: Participants who received at least 1 dose of natalizumab, had a negative baseline antibody result, and had at least 1 antibody assessment after the first dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Natalizumab High Titer | Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status | Antibody negative | 96 participants |
| Natalizumab High Titer | Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status | Transient positive | 3 participants |
| Natalizumab High Titer | Number of Participants With Anti-Natalizumab Antibody Negative, Transient Positive, and Persistent Positive Status | Persistent positive | 9 participants |
Secondary
Annualized Relapse Rate
Annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of years the participant was followed in the study. The annualized relapse rate was based only on those relapses that were determined to meet the definition of relapse per the investigator's clinical judgment. New or recurrent symptoms that occurred less than 30 days following the onset of a protocol-defined relapse were considered part of the same relapse.
Time frame: Through Week 36
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab High Titer | Annualized Relapse Rate | 0.13 relapses/participant-years |
Secondary
Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 36
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline.
Time frame: Baseline, Week 36
Population: Participants with EDSS scores at Baseline and Week 36 (includes participants who withdrew from the study).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Natalizumab High Titer | Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Week 36 | -0.19 scores on a scale | Standard Deviation 0.982 |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
AE: any sign, symptom, or diagnosis/disease that was unfavorable or unintended, new, or if pre-existing, worsened in a participant administered a study treatment and that did not necessarily have a causal relationship with this treatment. SAE: an event that resulted in death; an event that, in the view of the investigator, placed the participant at immediate risk of death (life-threatening event); an outcome that resulted in a congenital anomaly/birth defect diagnosed in a child of a participant in this study; an event that required or prolonged inpatient hospitalization; an event that resulted in persistent or significant disability/incapacity; any other medically important event that, in the opinion of the investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed above. Events were classified as 'related' or 'not related' to study drug, and categorized as 'mild' moderate' or 'severe' per protocol.
Time frame: AEs: collected from Baseline (Week 0) until Week 36 or premature withdrawal. SAEs: collected from informed consent until Week 36 or premature withdrawal.
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Adverse event (AE) | 106 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Moderate or severe AE | 63 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Severe AE | 18 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | AE related to study drug | 23 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Serious adverse event (SAE) | 7 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | SAE related to study drug | 0 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Treatment discontinuation due to AE | 4 participants |
| Natalizumab High Titer | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Withdrawal from study due to AE | 3 participants |