Trial Outcomes & Findings for Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® (NCT NCT04115488)

Last Updated: 2023-07-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

265 participants

Primary outcome timeframe

Scans performed at week 0 (baseline), week 8, 16, 20 and 24.

Results posted on

2023-07-03

Participant Flow

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).

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.

Participant milestones

Participant milestones
Measure	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.	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).
Overall Study STARTED	131	133
Overall Study Patients Re-randomized and Switched From Tysabri to PB006 at Week 24.	0	30
Overall Study Patients Continuing on Tysabri Following the Re-randomization at Week 24.	0	95
Overall Study COMPLETED	117	122
Overall Study NOT COMPLETED	14	11

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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).
Overall Study Adverse Event	8	4
Overall Study Withdrawal by Subject	3	6
Overall Study Investigator/ Sponsor Decision	2	0
Overall Study Patient 's location change	1	0
Overall Study Due to COVID-19 restrictions at site	0	1

Baseline Characteristics

Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PB006 n=131 Participants 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.	Tysabri n=133 Participants 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).	Total n=264 Participants Total of all reporting groups
Age, Continuous	36.8 Years STANDARD_DEVIATION 9.05 • n=5 Participants	36.6 Years STANDARD_DEVIATION 9.73 • n=7 Participants	36.7 Years STANDARD_DEVIATION 9.38 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	78 Participants n=7 Participants	162 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants	55 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	131 Participants n=5 Participants	133 Participants n=7 Participants	264 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	131 Participants n=5 Participants	133 Participants n=7 Participants	264 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=111 Participants 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.	Tysabri (Per-Protocol) n=118 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New Active Lesions Over 24 Weeks	1.4 lesions Standard Deviation 3.73	1.9 lesions Standard Deviation 3.97	1.4 lesions Standard Deviation 3.65	2.1 lesions Standard Deviation 3.78	1.9 lesions Standard Deviation 4.09

SECONDARY outcome

Timeframe: 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.

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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=96 Participants 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).	PB006 (Safety-Switch) n=119 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New Active Lesions Over 48 Weeks	1.5 lesions Standard Deviation 3.72	2.3 lesions Standard Deviation 5.68	1.5 lesions Standard Deviation 3.75	2.1 lesions Standard Deviation 3.82	2.3 lesions Standard Deviation 5.70

SECONDARY outcome

Timeframe: 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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=126 Participants 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.	Tysabri (Per-Protocol) n=127 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks	0.3 lesions Standard Deviation 1.01	0.4 lesions Standard Deviation 1.25	0.3 lesions Standard Deviation 1.02	0.4 lesions Standard Deviation 0.81	0.4 lesions Standard Deviation 1.37

SECONDARY outcome

Timeframe: 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.

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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=96 Participants 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).	PB006 (Safety-Switch) n=119 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks	0.3 lesions Standard Deviation 1.02	0.4 lesions Standard Deviation 1.39	0.3 lesions Standard Deviation 1.03	0.4 lesions Standard Deviation 0.82	0.4 lesions Standard Deviation 1.40

SECONDARY outcome

Timeframe: 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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=133 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks	109 Participants	105 Participants	105 Participants	23 Participants	80 Participants

SECONDARY outcome

Timeframe: 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.

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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=103 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks	105 Participants	80 Participants	102 Participants	22 Participants	79 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=126 Participants 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.	Tysabri (Per-Protocol) n=127 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks	1.5 lesions Standard Deviation 3.79	2.0 lesions Standard Deviation 4.12	1.5 lesions Standard Deviation 3.83	2.2 lesions Standard Deviation 3.84	2.0 lesions Standard Deviation 4.25

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=96 Participants 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).	PB006 (Safety-Switch) n=119 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks	1.6 lesions Standard Deviation 3.09	2.4 lesions Standard Deviation 5.79	1.6 lesions Standard Deviation 3.93	2.2 lesions Standard Deviation 3.89	2.5 lesions Standard Deviation 5.81

SECONDARY outcome

Timeframe: 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.

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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=126 Participants 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.	Tysabri (Per-Protocol) n=127 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Persistent Lesions After 24 Weeks	0.5 lesions Standard Deviation 2.46	0.4 lesions Standard Deviation 2.92	0.5 lesions Standard Deviation 2.49	0.1 lesions Standard Deviation 0.31	0.6 lesions Standard Deviation 3.37

SECONDARY outcome

Timeframe: 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.

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 \[mmol/kg\].

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=96 Participants 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).	PB006 (Safety-Switch) n=119 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Persistent Lesions After 48 Weeks	0.5 lesions Standard Deviation 2.55	0.6 lesions Standard Deviation 3.35	0.5 lesions Standard Deviation 2.58	0.1 lesions Standard Deviation 0.26	0.6 lesions Standard Deviation 3.37

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=133 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Annualized Relapse Rate After 24 Weeks	0.206 Relapses per patient-year	0.152 Relapses per patient-year	0.194 Relapses per patient-year	0.143 Relapses per patient-year	0.114 Relapses per patient-year

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=103 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Annualized Relapse Rate After 48 Weeks	0.174 Relapses per patient-year	0.133 Relapses per patient-year	0.168 Relapses per patient-year	0.146 Relapses per patient-year	0.113 Relapses per patient-year

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks	-0.03 score on a scale Standard Deviation 0.211	0.00 score on a scale Standard Deviation 0.354	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=93 Participants 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).	PB006 (Safety-Switch) n=117 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks	-0.14 score on a scale Standard Deviation 0.536	-0.05 score on a scale Standard Deviation 0.443	-0.10 score on a scale Standard Deviation 0.498	-0.03 score on a scale Standard Deviation 0.325	-0.02 score on a scale Standard Deviation 0.312

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks Persistently positive (confirmed)	28.7 Percentage of subjects	27.2 Percentage of subjects	28.7 Percentage of subjects	43.3 Percentage of subjects	22.1 Percentage of subjects
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks Positive, confirmed	30.3 Percentage of subjects	29.6 Percentage of subjects	30.3 Percentage of subjects	43.3 Percentage of subjects	25.3 Percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=115 Participants 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.	Tysabri (Per-Protocol) n=121 Participants 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).	PB006 (Safety-Switch) n=115 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=28 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks Persistently positive (confirmed)	10.4 Percentage of subjects	11.6 Percentage of subjects	10.4 Percentage of subjects	17.9 Percentage of subjects	9.7 Percentage of subjects
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks Positive, confirmed)	11.3 Percentage of subjects	11.6 Percentage of subjects	11.3 Percentage of subjects	17.9 Percentage of subjects	9.7 Percentage of subjects

SECONDARY outcome

Timeframe: Up to 24 weeks.

Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=37 Participants 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.	Tysabri (Per-Protocol) n=37 Participants 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).	PB006 (Safety-Switch) n=37 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=13 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=24 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Percentage of Subjects With Neutralizing Antibodies After 24 Weeks	67.6 Percentage of subjects	64.9 Percentage of subjects	67.6 Percentage of subjects	61.5 Percentage of subjects	66.7 Percentage of subjects

SECONDARY outcome

Timeframe: Up to 48 weeks.

Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=13 Participants 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.	Tysabri (Per-Protocol) n=14 Participants 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).	PB006 (Safety-Switch) n=13 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=5 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=9 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Percentage of Subjects With Neutralizing Antibodies After 48 Weeks	61.5 Percentage of subjects	50.0 Percentage of subjects	61.5 Percentage of subjects	60.0 Percentage of subjects	44.4 Percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=133 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks TEAE	62 participants	64 participants	—	—	—
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	0 participants	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=30 Participants 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).	PB006 (Safety-Switch) n=103 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks TEAE	85 participants	22 participants	71 participants	—	—
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	0 participants	2 participants	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=118 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 8	26804.75 Nanograms per milliliter (ng/mL) Standard Deviation 12949.541	25010.49 Nanograms per milliliter (ng/mL) Standard Deviation 12557.895	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=122 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 16	33872.92 Nanograms per milliliter (ng/mL) Standard Deviation 18151.190	32543.28 Nanograms per milliliter (ng/mL) Standard Deviation 14636.925	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=121 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 24	36853.93 Nanograms per milliliter (ng/mL) Standard Deviation 15292.389	35617.65 Nanograms per milliliter (ng/mL) Standard Deviation 16049.669	—	—	—

SECONDARY outcome

Timeframe: 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.

Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=115 Participants 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.	Tysabri (Per-Protocol) n=94 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 32	37450.04 Nanograms per milliliter (ng/mL) Standard Deviation 16877.010	36865.81 Nanograms per milliliter (ng/mL) Standard Deviation 19756.050	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=110 Participants 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.	Tysabri (Per-Protocol) n=91 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 48	39097.58 Nanograms per milliliter (ng/mL) Standard Deviation 16801.710	38432.86 Nanograms per milliliter (ng/mL) Standard Deviation 16495.407	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=133 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks	75 Participants	72 Participants	72 Participants	18 Participants	52 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=131 Participants 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.	Tysabri (Per-Protocol) n=103 Participants 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).	PB006 (Safety-Switch) n=122 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=30 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=95 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks	71 Participants	52 Participants	69 Participants	17 Participants	51 Participants

SECONDARY outcome

Timeframe: 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).

Number of patients with abnormal clinical laboratory tests at week 24.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients With Abnormal Clinical Laboratory Tests at Week 24	116 Participants	114 Participants	—	—	—

SECONDARY outcome

Timeframe: 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.

Number of patients with abnormal clinical laboratory tests at week 48.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=29 Participants 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).	PB006 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients With Abnormal Clinical Laboratory Tests at Week 48	108 Participants	26 Participants	88 Participants	—	—

SECONDARY outcome

Timeframe: 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).

Number of patients with abnormal findings in physical examination at week 24.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients With Abnormal Findings in Physical Examination at Week 24	10 Participants	12 Participants	—	—	—

SECONDARY outcome

Timeframe: 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.

Number of patients with abnormal findings in physical examination at week 48.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=122 Participants 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).	PB006 (Safety-Switch) n=117 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) n=29 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Number of Patients With Abnormal Findings in Physical Examination at Week 48	11 Participants	10 Participants	11 Participants	3 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

Change from baseline in diastolic and systolic blood Pressure at week 24.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Blood Pressure at Week 24 Diastolic Blood Pressure	-2.2 Millimeter of mercury (mmHg) Standard Deviation 7.30	-0.6 Millimeter of mercury (mmHg) Standard Deviation 7.35	—	—	—
Change From Baseline in Blood Pressure at Week 24 Systolic Blood Pressure	-1.0 Millimeter of mercury (mmHg) Standard Deviation 9.76	-1.5 Millimeter of mercury (mmHg) Standard Deviation 11.33	—	—	—

SECONDARY outcome

Timeframe: 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.

Change from baseline in diastolic and systolic blood Pressure at week 48.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=29 Participants 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).	PB006 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Blood Pressure at Week 48 Diastolic Blood Pressure	1.0 Millimeter of mercury (mmHg) Standard Deviation 7.58	1.8 Millimeter of mercury (mmHg) Standard Deviation 8.16	0.8 Millimeter of mercury (mmHg) Standard Deviation 7.68	—	—
Change From Baseline in Blood Pressure at Week 48 Systolic Blood Pressure	1.7 Millimeter of mercury (mmHg) Standard Deviation 8.67	2.4 Millimeter of mercury (mmHg) Standard Deviation 12.38	3.0 Millimeter of mercury (mmHg) Standard Deviation 10.18	—	—

SECONDARY outcome

Timeframe: At baseline and week 24.

Change from baseline in heart rate at week 24.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=122 Participants 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.	Tysabri (Per-Protocol) n=125 Participants 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).	PB006 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Heart Rate at Week 24	-0.4 beats/minute Standard Deviation 9.05	-1.4 beats/minute Standard Deviation 9.10	—	—	—

SECONDARY outcome

Timeframe: 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.

Change from baseline in heart rate at week 48.

Outcome measures

Outcome measures
Measure	PB006 (Per-Protocol) n=117 Participants 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.	Tysabri (Per-Protocol) n=29 Participants 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).	PB006 (Safety-Switch) n=93 Participants Patients with relapsing-remitting multiple sclerosis (RRMS) received 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.	Tysabri Switched to PB006 at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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). This arm concerns patients who started on Tysabri and continued on PB006 following the re-randomization at week 24.	Tysabri Continued at Week 24 (Safety-Switch) Patients with relapsing-remitting multiple sclerosis (RRMS) received 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. This arm concerns patients who started on Tysabri and continued on Tysabri following the re-randomization at week 24.
Change From Baseline in Heart Rate at Week 48	0.8 beats/minute Standard Deviation 7.07	1.7 beats/minute Standard Deviation 10.53	1.1 beats/minute Standard Deviation 9.66	—	—

Adverse Events

PB006

Serious events: 3 serious events

Other events: 100 other events

Deaths: 0 deaths

Tysabri

Serious events: 2 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PB006 n=161 participants at risk 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. This arm includes patients who switched from Tysabri to PB006 during the re-randomization step at week 24.	Tysabri n=133 participants at risk 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).
Vascular disorders Hypotension	0.62% 1/161 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).	0.00% 0/133 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
Nervous system disorders Tremor	0.00% 0/161 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).	0.75% 1/133 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.62% 1/161 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).	0.00% 0/133 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/161 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).	0.75% 1/133 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
Infections and infestations Pneumonia	0.62% 1/161 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).	0.00% 0/133 • From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks. Patients participating in this study who receive at least one (complete or partial) infusion of the study drug were included in the Safety Population (SAF).

Other adverse events

Additional Information

Director Clinical Research and Development

Polpharma Biologics S.A.

Phone: +48 607 697 896

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place