Relapsing-Remitting Multiple Sclerosis (RRMS)
Conditions
Brief summary
This is a multi-center, randomized, parallel arm, double-blind study with a total duration of subjects' participation of 48 weeks. Approximately 260 participants with relapsing-remitting multiple sclerosis will be randomized to receive 12 doses of either PB006 or EU-licensed Natalizumab.
Detailed description
This is a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the equivalence in efficacy and similarity in safety of biosimilar PB006 compared to Tysabri in patients with RRMS. All eligible patients will be randomly assigned to one of two treatment groups in a 1:1 ratio, to receive a total of twelve intravenous (IV) infusion of either PB006 or Tysabri at a dose of 300 mg at each intravenous (IV) infusion administered with every single one intravenous (IV) infusion administered every 4 weeks of either PB006 or Tysabri at a dose of 300 mg starting at visit 1 (week 0) through visit 12 (week 44), for a total of 12 infusions. The End-of-Study Visit (visit 13, week 48) will be performed 4 weeks after the last infusion
Interventions
BIOLOGICALIntravenous (IV) infusions
Intravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses
Sponsors
Polpharma Biologics S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients (age ≥18 to 60 years), with relapsing-remitting multiple sclerosis (RRMS) defined by the 2010 revised McDonald criteria * At least 1 documented relapse within the previous year and either ≥1 GdE T1-weighted brain lesions or ≥9 T2-weighted brain lesions at Screening * Kurtzke Expanded Disability Status Scale (EDSS) score from 0 to 5 (inclusive) at Screening
Exclusion criteria
* Manifestation of multiple sclerosis (MS) other than relapsing-remitting multiple sclerosis (RRMS) * Relapse within the 30 days prior Screening and until administration of the first dose of study drug * Prior treatment with natalizumab, alemtuzumab, ocrelizumab, daclizumab, rituximab, cladribine, or other B- and T-cell targeting therapies * Prior total lymphoid irradiation or bone marrow or organ transplantation * Patients with John Cunningham Virus (JCV) index \>1.5 at Screening * Past or current Progressive Multi-focal leukoencephalopathy (PML) diagnosis * Severe renal function impairment as defined by serum creatinine values \>120 micromol per litre
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of New Active Lesions Over 24 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20 and 24. | Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20 and 24. | Cumulative number of new GdE T1-weighted lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Cumulative number of new GdE T1-weighted lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20 and 24. | Number of patients without new GdE T1-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Number of patients without new GdE T1-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20 and 24. | Cumulative number of new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. |
| Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Cumulative number of new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. |
| Number of Persistent Lesions After 24 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20 and 24. | Number of persistent lesions after 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Number of Persistent Lesions After 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Number of persistent lesions after 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Annualized Relapse Rate After 24 Weeks | Up to 24 weeks. | Annualized relapse rate after 24 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group. |
| Annualized Relapse Rate After 48 Weeks | Up to 48 weeks. | Annualized relapse rate after 48 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group. |
| Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks | Baseline and week 24. | Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in multiple sclerosis (MS), is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus other) are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. After re-randomization, Week 24 is considered baseline. |
| Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48. | Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in MS, is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus other) are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. |
| Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Up to 24 weeks. | Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits. |
| Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Up to 48 weeks. | Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits. |
| Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | Up to 24 weeks. | Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks. |
| Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | Up to 48 weeks. | Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks. |
| Cumulative Number of New Active Lesions Over 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Cumulative number of new active lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent was administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\]. |
| Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | Up to 48 weeks. | Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks. |
| Natalizumab Trough Concentration (Ctrough) Over Time, Week 8 | Week 8 | Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient. |
| Natalizumab Trough Concentration (Ctrough) Over Time, Week 16 | Week 16 | Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient. |
| Natalizumab Trough Concentration (Ctrough) Over Time, Week 24 | Week 24 | Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient. |
| Natalizumab Trough Concentration (Ctrough) Over Time, Week 32 | Week 32 | Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient. |
| Natalizumab Trough Concentration (Ctrough) Over Time, Week 48 | Week 48 | Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient. |
| Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | Week 0 (baseline), week 8, 16, 20 and 24. | Number of patients without new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. |
| Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. | Number of patients without new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. |
| Number of Patients With Abnormal Clinical Laboratory Tests at Week 24 | At week 24. | Number of patients with abnormal clinical laboratory tests at week 24. |
| Number of Patients With Abnormal Clinical Laboratory Tests at Week 48 | At week 48. | Number of patients with abnormal clinical laboratory tests at week 48. |
| Number of Patients With Abnormal Findings in Physical Examination at Week 24 | Week 24. | Number of patients with abnormal findings in physical examination at week 24. |
| Number of Patients With Abnormal Findings in Physical Examination at Week 48 | End of study (week 48). | Number of patients with abnormal findings in physical examination at week 48. |
| Change From Baseline in Blood Pressure at Week 24 | At baseline and week 24. | Change from baseline in diastolic and systolic blood Pressure at week 24. |
| Change From Baseline in Blood Pressure at Week 48 | At baseline and end of study (week 48). | Change from baseline in diastolic and systolic blood Pressure at week 48. |
| Change From Baseline in Heart Rate at Week 24 | At baseline and week 24. | Change from baseline in heart rate at week 24. |
| Change From Baseline in Heart Rate at Week 48 | At baseline and end of study (week 48). | Change from baseline in heart rate at week 48. |
| Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks | Up to week 24 | Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks. |
Countries
Belarus, Croatia, Georgia, Moldova, Poland, Serbia, Ukraine
Participant flow
Recruitment details
This was a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the similarity in efficacy, safety, and immunogenicity of biosimilar natalizumab PB006 compared to European Union-approved Tysabri in patients with Relapsing-remitting multiple sclerosis (RRMS).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. One subject withdrew consent before receiving study drug and was not included in the results.
Participants by arm
| Arm | Count |
|---|---|
| PB006 Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. | 131 |
| Tysabri Patients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. At Week 24, patients in the Tysabri group were re-randomized through a re-randomization step. Patients re-randomized and switched from Tysabri to PB006 at Week 24 still received a total of 12 infusions (6 infusions of Tysabri and 6 infusions of PB006). | 133 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 |
| Overall Study | Due to COVID-19 restrictions at site | 0 | 1 |
| Overall Study | Investigator/ Sponsor Decision | 2 | 0 |
| Overall Study | Patient 's location change | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Tysabri | Total | PB006 |
|---|---|---|---|
| Age, Continuous | 36.6 Years STANDARD_DEVIATION 9.73 | 36.7 Years STANDARD_DEVIATION 9.38 | 36.8 Years STANDARD_DEVIATION 9.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 133 Participants | 264 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 133 Participants | 264 Participants | 131 Participants |
| Sex: Female, Male Female | 78 Participants | 162 Participants | 84 Participants |
| Sex: Female, Male Male | 55 Participants | 102 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 133 |
| other Total, other adverse events | 100 / 161 | 93 / 133 |
| serious Total, serious adverse events | 3 / 161 | 2 / 133 |
Outcome results
Primary
Cumulative Number of New Active Lesions Over 24 Weeks
Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Population: Per-Protocol: patients who completed the 24-week treatment period without major protocol deviations that may have influenced the analysis of the primary endpoint and for whom sufficient post-baseline MRI data were available (baseline, Week 24 and at least 1/3 MRI visits). Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not. Subjects with non-missing endpoints in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New Active Lesions Over 24 Weeks | 1.4 lesions | Standard Deviation 3.73 |
| Tysabri (Per-Protocol) | Cumulative Number of New Active Lesions Over 24 Weeks | 1.9 lesions | Standard Deviation 3.97 |
| PB006 (Safety-Switch) | Cumulative Number of New Active Lesions Over 24 Weeks | 1.4 lesions | Standard Deviation 3.65 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New Active Lesions Over 24 Weeks | 2.1 lesions | Standard Deviation 3.78 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New Active Lesions Over 24 Weeks | 1.9 lesions | Standard Deviation 4.09 |
95% CI: [-0.613, 0.944]
Secondary
Annualized Relapse Rate After 24 Weeks
Annualized relapse rate after 24 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
Time frame: Up to 24 weeks.
Population: Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PB006 (Per-Protocol) | Annualized Relapse Rate After 24 Weeks | 0.206 Relapses per patient-year |
| Tysabri (Per-Protocol) | Annualized Relapse Rate After 24 Weeks | 0.152 Relapses per patient-year |
| PB006 (Safety-Switch) | Annualized Relapse Rate After 24 Weeks | 0.194 Relapses per patient-year |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Annualized Relapse Rate After 24 Weeks | 0.143 Relapses per patient-year |
| Tysabri Continued at Week 24 (Safety-Switch) | Annualized Relapse Rate After 24 Weeks | 0.114 Relapses per patient-year |
Secondary
Annualized Relapse Rate After 48 Weeks
Annualized relapse rate after 48 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
Time frame: Up to 48 weeks.
Population: Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PB006 (Per-Protocol) | Annualized Relapse Rate After 48 Weeks | 0.174 Relapses per patient-year |
| Tysabri (Per-Protocol) | Annualized Relapse Rate After 48 Weeks | 0.133 Relapses per patient-year |
| PB006 (Safety-Switch) | Annualized Relapse Rate After 48 Weeks | 0.168 Relapses per patient-year |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Annualized Relapse Rate After 48 Weeks | 0.146 Relapses per patient-year |
| Tysabri Continued at Week 24 (Safety-Switch) | Annualized Relapse Rate After 48 Weeks | 0.113 Relapses per patient-year |
Secondary
Change From Baseline in Blood Pressure at Week 24
Change from baseline in diastolic and systolic blood Pressure at week 24.
Time frame: At baseline and week 24.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Blood Pressure at Week 24 | Diastolic Blood Pressure | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 7.3 |
| PB006 (Per-Protocol) | Change From Baseline in Blood Pressure at Week 24 | Systolic Blood Pressure | -1.0 Millimeter of mercury (mmHg) | Standard Deviation 9.76 |
| Tysabri (Per-Protocol) | Change From Baseline in Blood Pressure at Week 24 | Diastolic Blood Pressure | -0.6 Millimeter of mercury (mmHg) | Standard Deviation 7.35 |
| Tysabri (Per-Protocol) | Change From Baseline in Blood Pressure at Week 24 | Systolic Blood Pressure | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 11.33 |
Secondary
Change From Baseline in Blood Pressure at Week 48
Change from baseline in diastolic and systolic blood Pressure at week 48.
Time frame: At baseline and end of study (week 48).
Population: Safety-Switch Population: Patients who were included in the SAF and received at least 1 infusion of the study drug after the timepoint of re-randomization, independent of whether they switched or not, were included in the Safety-Switch Population (SSW). Patients in this group were analyzed as treated after re-randomization, also considering treatment before re-randomization.~Tysabri (SSW): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Blood Pressure at Week 48 | Diastolic Blood Pressure | 1.0 Millimeter of mercury (mmHg) | Standard Deviation 7.58 |
| PB006 (Per-Protocol) | Change From Baseline in Blood Pressure at Week 48 | Systolic Blood Pressure | 1.7 Millimeter of mercury (mmHg) | Standard Deviation 8.67 |
| Tysabri (Per-Protocol) | Change From Baseline in Blood Pressure at Week 48 | Diastolic Blood Pressure | 1.8 Millimeter of mercury (mmHg) | Standard Deviation 8.16 |
| Tysabri (Per-Protocol) | Change From Baseline in Blood Pressure at Week 48 | Systolic Blood Pressure | 2.4 Millimeter of mercury (mmHg) | Standard Deviation 12.38 |
| PB006 (Safety-Switch) | Change From Baseline in Blood Pressure at Week 48 | Diastolic Blood Pressure | 0.8 Millimeter of mercury (mmHg) | Standard Deviation 7.68 |
| PB006 (Safety-Switch) | Change From Baseline in Blood Pressure at Week 48 | Systolic Blood Pressure | 3.0 Millimeter of mercury (mmHg) | Standard Deviation 10.18 |
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks
Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in multiple sclerosis (MS), is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus other) are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. After re-randomization, Week 24 is considered baseline.
Time frame: Baseline and week 24.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks | -0.03 score on a scale | Standard Deviation 0.211 |
| Tysabri (Per-Protocol) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks | 0.00 score on a scale | Standard Deviation 0.354 |
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks
Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in MS, is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus other) are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists.
Time frame: FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.
Population: Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | -0.14 score on a scale | Standard Deviation 0.536 |
| Tysabri (Per-Protocol) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | -0.05 score on a scale | Standard Deviation 0.443 |
| PB006 (Safety-Switch) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | -0.10 score on a scale | Standard Deviation 0.498 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | -0.03 score on a scale | Standard Deviation 0.325 |
| Tysabri Continued at Week 24 (Safety-Switch) | Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks | -0.02 score on a scale | Standard Deviation 0.312 |
Secondary
Change From Baseline in Heart Rate at Week 24
Change from baseline in heart rate at week 24.
Time frame: At baseline and week 24.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Heart Rate at Week 24 | -0.4 beats/minute | Standard Deviation 9.05 |
| Tysabri (Per-Protocol) | Change From Baseline in Heart Rate at Week 24 | -1.4 beats/minute | Standard Deviation 9.1 |
Secondary
Change From Baseline in Heart Rate at Week 48
Change from baseline in heart rate at week 48.
Time frame: At baseline and end of study (week 48).
Population: Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Change From Baseline in Heart Rate at Week 48 | 0.8 beats/minute | Standard Deviation 7.07 |
| Tysabri (Per-Protocol) | Change From Baseline in Heart Rate at Week 48 | 1.7 beats/minute | Standard Deviation 10.53 |
| PB006 (Safety-Switch) | Change From Baseline in Heart Rate at Week 48 | 1.1 beats/minute | Standard Deviation 9.66 |
Secondary
Cumulative Number of New Active Lesions Over 48 Weeks
Cumulative number of new active lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent was administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not. Subjects with non-missing endpoints in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New Active Lesions Over 48 Weeks | 1.5 lesions | Standard Deviation 3.72 |
| Tysabri (Per-Protocol) | Cumulative Number of New Active Lesions Over 48 Weeks | 2.3 lesions | Standard Deviation 5.68 |
| PB006 (Safety-Switch) | Cumulative Number of New Active Lesions Over 48 Weeks | 1.5 lesions | Standard Deviation 3.75 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New Active Lesions Over 48 Weeks | 2.1 lesions | Standard Deviation 3.82 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New Active Lesions Over 48 Weeks | 2.3 lesions | Standard Deviation 5.7 |
Secondary
Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks
Cumulative number of new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Population: The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | 1.5 lesions | Standard Deviation 3.79 |
| Tysabri (Per-Protocol) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | 2.0 lesions | Standard Deviation 4.12 |
| PB006 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | 1.5 lesions | Standard Deviation 3.83 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | 2.2 lesions | Standard Deviation 3.84 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks | 2.0 lesions | Standard Deviation 4.25 |
Secondary
Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks
Cumulative number of new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | 1.6 lesions | Standard Deviation 3.09 |
| Tysabri (Per-Protocol) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | 2.4 lesions | Standard Deviation 5.79 |
| PB006 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | 1.6 lesions | Standard Deviation 3.93 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | 2.2 lesions | Standard Deviation 3.89 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks | 2.5 lesions | Standard Deviation 5.81 |
Secondary
Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks
Cumulative number of new GdE T1-weighted lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not. Subjects with non-missing endpoints in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | 0.3 lesions | Standard Deviation 1.01 |
| Tysabri (Per-Protocol) | Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | 0.4 lesions | Standard Deviation 1.25 |
| PB006 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | 0.3 lesions | Standard Deviation 1.02 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | 0.4 lesions | Standard Deviation 0.81 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks | 0.4 lesions | Standard Deviation 1.37 |
Secondary
Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks
Cumulative number of new GdE T1-weighted lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set (FAS) population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch (SSW) Population: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | 0.3 lesions | Standard Deviation 1.02 |
| Tysabri (Per-Protocol) | Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | 0.4 lesions | Standard Deviation 1.39 |
| PB006 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | 0.3 lesions | Standard Deviation 1.03 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | 0.4 lesions | Standard Deviation 0.82 |
| Tysabri Continued at Week 24 (Safety-Switch) | Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks | 0.4 lesions | Standard Deviation 1.4 |
Secondary
Natalizumab Trough Concentration (Ctrough) Over Time, Week 16
Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Time frame: Week 16
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 16 | 33872.92 Nanograms per milliliter (ng/mL) | Standard Deviation 18151.19 |
| Tysabri (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 16 | 32543.28 Nanograms per milliliter (ng/mL) | Standard Deviation 14636.925 |
Secondary
Natalizumab Trough Concentration (Ctrough) Over Time, Week 24
Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Time frame: Week 24
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 24 | 36853.93 Nanograms per milliliter (ng/mL) | Standard Deviation 15292.389 |
| Tysabri (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 24 | 35617.65 Nanograms per milliliter (ng/mL) | Standard Deviation 16049.669 |
Secondary
Natalizumab Trough Concentration (Ctrough) Over Time, Week 32
Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Time frame: Week 32
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis. For this outcome measure, only participants who remain in the same treatment group through study period were included.~Only patients who stayed on their randomized treatment were included in the endpoint, patients who switch from Tysabri to PB006 were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 32 | 37450.04 Nanograms per milliliter (ng/mL) | Standard Deviation 16877.01 |
| Tysabri (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 32 | 36865.81 Nanograms per milliliter (ng/mL) | Standard Deviation 19756.05 |
Secondary
Natalizumab Trough Concentration (Ctrough) Over Time, Week 48
Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Time frame: Week 48
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis. For this outcome measure, only participants who remain in the same treatment group through study period were included.~Only patients who stayed on their randomized treatment were included in the endpoint, patients who switch from Tysabri to PB006 were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 48 | 39097.58 Nanograms per milliliter (ng/mL) | Standard Deviation 16801.71 |
| Tysabri (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 48 | 38432.86 Nanograms per milliliter (ng/mL) | Standard Deviation 16495.407 |
Secondary
Natalizumab Trough Concentration (Ctrough) Over Time, Week 8
Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Time frame: Week 8
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 8 | 26804.75 Nanograms per milliliter (ng/mL) | Standard Deviation 12949.541 |
| Tysabri (Per-Protocol) | Natalizumab Trough Concentration (Ctrough) Over Time, Week 8 | 25010.49 Nanograms per milliliter (ng/mL) | Standard Deviation 12557.895 |
Secondary
Number of Patients With Abnormal Clinical Laboratory Tests at Week 24
Number of patients with abnormal clinical laboratory tests at week 24.
Time frame: At week 24.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients With Abnormal Clinical Laboratory Tests at Week 24 | 116 Participants |
| Tysabri (Per-Protocol) | Number of Patients With Abnormal Clinical Laboratory Tests at Week 24 | 114 Participants |
Secondary
Number of Patients With Abnormal Clinical Laboratory Tests at Week 48
Number of patients with abnormal clinical laboratory tests at week 48.
Time frame: At week 48.
Population: Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients With Abnormal Clinical Laboratory Tests at Week 48 | 108 Participants |
| Tysabri (Per-Protocol) | Number of Patients With Abnormal Clinical Laboratory Tests at Week 48 | 26 Participants |
| PB006 (Safety-Switch) | Number of Patients With Abnormal Clinical Laboratory Tests at Week 48 | 88 Participants |
Secondary
Number of Patients With Abnormal Findings in Physical Examination at Week 24
Number of patients with abnormal findings in physical examination at week 24.
Time frame: Week 24.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients With Abnormal Findings in Physical Examination at Week 24 | 10 Participants |
| Tysabri (Per-Protocol) | Number of Patients With Abnormal Findings in Physical Examination at Week 24 | 12 Participants |
Secondary
Number of Patients With Abnormal Findings in Physical Examination at Week 48
Number of patients with abnormal findings in physical examination at week 48.
Time frame: End of study (week 48).
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF).~Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switched or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients With Abnormal Findings in Physical Examination at Week 48 | 11 Participants |
| Tysabri (Per-Protocol) | Number of Patients With Abnormal Findings in Physical Examination at Week 48 | 10 Participants |
| PB006 (Safety-Switch) | Number of Patients With Abnormal Findings in Physical Examination at Week 48 | 11 Participants |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Patients With Abnormal Findings in Physical Examination at Week 48 | 3 Participants |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Patients With Abnormal Findings in Physical Examination at Week 48 | 7 Participants |
Secondary
Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks
Number of patients without new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Time frame: Week 0 (baseline), week 8, 16, 20 and 24.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | 75 Participants |
| Tysabri (Per-Protocol) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | 72 Participants |
| PB006 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | 72 Participants |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | 18 Participants |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks | 52 Participants |
Secondary
Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks
Number of patients without new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | 71 Participants |
| Tysabri (Per-Protocol) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | 52 Participants |
| PB006 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | 69 Participants |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | 17 Participants |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks | 51 Participants |
Secondary
Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks
Number of patients without new GdE T1-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | 109 Participants |
| Tysabri (Per-Protocol) | Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | 105 Participants |
| PB006 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | 105 Participants |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | 23 Participants |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks | 80 Participants |
Secondary
Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks
Number of patients without new GdE T1-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PB006 (Per-Protocol) | Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | 105 Participants |
| Tysabri (Per-Protocol) | Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | 80 Participants |
| PB006 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | 102 Participants |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | 22 Participants |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks | 79 Participants |
Secondary
Number of Persistent Lesions After 24 Weeks
Number of persistent lesions after 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch : treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Number of Persistent Lesions After 24 Weeks | 0.5 lesions | Standard Deviation 2.46 |
| Tysabri (Per-Protocol) | Number of Persistent Lesions After 24 Weeks | 0.4 lesions | Standard Deviation 2.92 |
| PB006 (Safety-Switch) | Number of Persistent Lesions After 24 Weeks | 0.5 lesions | Standard Deviation 2.49 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Persistent Lesions After 24 Weeks | 0.1 lesions | Standard Deviation 0.31 |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Persistent Lesions After 24 Weeks | 0.6 lesions | Standard Deviation 3.37 |
Secondary
Number of Persistent Lesions After 48 Weeks
Number of persistent lesions after 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram \[mmol/kg\].
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Population: The Full Analysis Set: patients who were randomized and have received at least one (complete or partial) infusion of the study drug. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.~Tysabri (FAS): Patients who switch from Tysabri to PB006 are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PB006 (Per-Protocol) | Number of Persistent Lesions After 48 Weeks | 0.5 lesions | Standard Deviation 2.55 |
| Tysabri (Per-Protocol) | Number of Persistent Lesions After 48 Weeks | 0.6 lesions | Standard Deviation 3.35 |
| PB006 (Safety-Switch) | Number of Persistent Lesions After 48 Weeks | 0.5 lesions | Standard Deviation 2.58 |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Number of Persistent Lesions After 48 Weeks | 0.1 lesions | Standard Deviation 0.26 |
| Tysabri Continued at Week 24 (Safety-Switch) | Number of Persistent Lesions After 48 Weeks | 0.6 lesions | Standard Deviation 3.37 |
Secondary
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks.
Time frame: Up to week 24
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PB006 (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks | TEAE | 62 participants |
| PB006 (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks | Treatment-emergent SAE | 1 participants |
| Tysabri (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks | TEAE | 64 participants |
| Tysabri (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks | Treatment-emergent SAE | 0 participants |
Secondary
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks.
Time frame: Up to 48 weeks.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PB006 (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | TEAE | 85 participants |
| PB006 (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | Treatment-emergent SAE | 3 participants |
| Tysabri (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | TEAE | 22 participants |
| Tysabri (Per-Protocol) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | Treatment-emergent SAE | 0 participants |
| PB006 (Safety-Switch) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | TEAE | 71 participants |
| PB006 (Safety-Switch) | Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks | Treatment-emergent SAE | 2 participants |
Secondary
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
Time frame: Up to 24 weeks.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PB006 (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Persistently positive (confirmed) | 28.7 Percentage of subjects |
| PB006 (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Positive, confirmed | 30.3 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Persistently positive (confirmed) | 27.2 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Positive, confirmed | 29.6 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Persistently positive (confirmed) | 28.7 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Positive, confirmed | 30.3 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Positive, confirmed | 43.3 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Persistently positive (confirmed) | 43.3 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Persistently positive (confirmed) | 22.1 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks | Positive, confirmed | 25.3 Percentage of subjects |
Secondary
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
Time frame: Up to 48 weeks.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PB006 (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Persistently positive (confirmed) | 10.4 Percentage of subjects |
| PB006 (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Positive, confirmed) | 11.3 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Persistently positive (confirmed) | 11.6 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Positive, confirmed) | 11.6 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Persistently positive (confirmed) | 10.4 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Positive, confirmed) | 11.3 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Positive, confirmed) | 17.9 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Persistently positive (confirmed) | 17.9 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Persistently positive (confirmed) | 9.7 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks | Positive, confirmed) | 9.7 Percentage of subjects |
Secondary
Percentage of Subjects With Neutralizing Antibodies After 24 Weeks
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks.
Time frame: Up to 24 weeks.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PB006 (Per-Protocol) | Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | 67.6 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | 64.9 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | 67.6 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | 61.5 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 24 Weeks | 66.7 Percentage of subjects |
Secondary
Percentage of Subjects With Neutralizing Antibodies After 48 Weeks
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks.
Time frame: Up to 48 weeks.
Population: Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated. Safety-Switch: treated patients who received at least one infusion of the study drug after the time point of re-randomization, independent of whether they switch or not. Only subjects with non-missing endpoints were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PB006 (Per-Protocol) | Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | 61.5 Percentage of subjects |
| Tysabri (Per-Protocol) | Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | 50.0 Percentage of subjects |
| PB006 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | 61.5 Percentage of subjects |
| Tysabri Switched to PB006 at Week 24 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | 60.0 Percentage of subjects |
| Tysabri Continued at Week 24 (Safety-Switch) | Percentage of Subjects With Neutralizing Antibodies After 48 Weeks | 44.4 Percentage of subjects |