Clinical Trial Results:
Antelope: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS)
Summary
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EudraCT number |
2018-004751-20 |
Trial protocol |
PL HR |
Global end of trial date |
23 Aug 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2022
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First version publication date |
29 Mar 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PB006-03-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04115488 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Polpharma Biologics S.A.
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Sponsor organisation address |
ul. Trzy Lipy 3, Gdańsk, Poland, 80-172
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Public contact |
Karsten Roth, Director Clinical Research and Development, Polpharma Biologics S.A., +48 607 697 896, clinicaltrials@polpharmabiologics.com
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Scientific contact |
Karsten Roth, Director Clinical Research and Development, Polpharma Biologics S.A., +48 607 697 896, clinicaltrials@polpharmabiologics.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Oct 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Aug 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate and compare the cumulative number of new active lesions
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Jun 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 59
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Country: Number of subjects enrolled |
Croatia: 2
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Country: Number of subjects enrolled |
Belarus: 49
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Country: Number of subjects enrolled |
Moldova, Republic of: 2
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Country: Number of subjects enrolled |
Serbia: 24
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Country: Number of subjects enrolled |
Ukraine: 99
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Country: Number of subjects enrolled |
Georgia: 30
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Worldwide total number of subjects |
265
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EEA total number of subjects |
61
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
265
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This was a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the similarity in efficacy, safety, and immunogenicity of biosimilar natalizumab PB006 compared to European Union-approved Tysabri in patients with Relapsing-remitting multiple sclerosis (RRMS). | ||||||||||||||||||
Pre-assignment
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Screening details |
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. | ||||||||||||||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Investigator, Monitor, Data analyst, Carer, Subject, Assessor | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PB006 | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
PB006
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg).
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Arm title
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Tysabri | ||||||||||||||||||
Arm description |
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). | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Tysabri
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Investigational medicinal product code |
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Other name |
natalizumab
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of Tysabri at a dose of 300 milligram (mg).
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Investigational medicinal product name |
PB006
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients with relapsing-remitting multiple sclerosis (RRMS) received IV infusions every 4 weeks of PB006 at a dose of 300 milligram (mg).
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Out of the 265 enrolled subjects, 264 were randomized. |
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Baseline characteristics reporting groups
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Reporting group title |
PB006
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tysabri
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Reporting group description |
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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PB006
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Reporting group description |
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. | ||
Reporting group title |
Tysabri
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Reporting group description |
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). | ||
Subject analysis set title |
PB006 (SSW)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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.
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 switched or not.
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Subject analysis set title |
Tysabri Switched to PB006 at week 24 (SSW)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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. 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 switched or not.
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Subject analysis set title |
Tysabri continued at week 24 (SSW)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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. 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 switched or not.
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Subject analysis set title |
PB006 (SAF)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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. 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.
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Subject analysis set title |
Tysabri Switched to PB006 at week 24 (SAF)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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. 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.
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Subject analysis set title |
Tysabri continued at week 24 (SAF)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
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. 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.
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End point title |
Cumulative number of new active lesions over 24 weeks | ||||||||||||||||||||||||
End point description |
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.
Per-Protocol Population (PP): 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 (incl baseline, Week 24 and at least 1/3 MRI visits).
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 switched or not.
Only subjects with non-missing endpoints were included in the analysis.
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End point type |
Primary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
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Notes [1] - PP [2] - PP [3] - SSW [4] - SSW [5] - SSW |
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Statistical analysis title |
Primary Efficacy Analysis | ||||||||||||||||||||||||
Statistical analysis description |
Data was analyzed using a negative binomial model with a logarithmic link function and fixed effects for the treatment group and stratification factors. Equivalence was tested based 95% confidence interval. Difference calculated as Tysabri minus PB006.
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Comparison groups |
PB006 v Tysabri
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Number of subjects included in analysis |
253
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||||||
Method |
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Parameter type |
Exponentiated Difference | ||||||||||||||||||||||||
Point estimate |
0.17
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.613 | ||||||||||||||||||||||||
upper limit |
0.944 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.397
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End point title |
Cumulative number of new active lesions over 48 weeks | ||||||||||||||||||||||||
End point description |
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].
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
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Notes [6] - FAS [7] - FAS, patients who switch from Tysabri to PB006 are excluded. [8] - SSW [9] - SSW [10] - SSW |
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No statistical analyses for this end point |
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End point title |
Cumulative number of new GdE T1-weighted lesions over 24 weeks | ||||||||||||||||||||||||
End point description |
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].
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
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Notes [11] - FAS [12] - FAS [13] - FAS [14] - FAS [15] - FAS |
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No statistical analyses for this end point |
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End point title |
Cumulative number of new GdE T1-weighted lesions over 48 weeks | ||||||||||||||||||||||||
End point description |
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].
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
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Notes [16] - FAS [17] - FAS [18] - SSW [19] - SSW [20] - SSW |
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No statistical analyses for this end point |
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End point title |
Number of patients without new GdE T1-weighted lesions over 24 weeks | ||||||||||||||||||
End point description |
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].
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
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Notes [21] - FAS [22] - FAS [23] - SSW [24] - SSW [25] - SSW |
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No statistical analyses for this end point |
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End point title |
Number of patients without new GdE T1-weighted lesions over 48 weeks | ||||||||||||||||||
End point description |
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].
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
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Notes [26] - FAS [27] - FAS, patients who switch from Tysabri to PB006 are excluded. [28] - SSW [29] - SSW [30] - SSW |
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No statistical analyses for this end point |
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End point title |
Cumulative number of new/enlarging T2-weighted lesions over 24 weeks | ||||||||||||||||||||||||
End point description |
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.
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.
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End point type |
Secondary
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End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [31] - FAS [32] - FAS [33] - SSW [34] - SSW [35] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Cumulative number of new/enlarging T2-weighted lesions over 48 weeks | ||||||||||||||||||||||||
End point description |
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.
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [36] - FAS [37] - FAS, patients who switch from Tysabri to PB006 are excluded. [38] - SSW [39] - SSW [40] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of persistent lesions after 24 weeks | ||||||||||||||||||||||||
End point description |
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].
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [41] - FAS [42] - FAS [43] - SSW [44] - SSW [45] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of persistent lesions after 48 weeks | ||||||||||||||||||||||||
End point description |
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].
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [46] - FAS [47] - FAS, patients who switch from Tysabri to PB006 are excluded. [48] - SSW [49] - SSW [50] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Annualized relapse rate after 24 weeks | ||||||||||||||||||||||||
End point description |
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 per patient. B: Duration of follow-up time per patient,
defined as: (last day of follow-up - day of randomization + 1) / 365.25. Relapses per patient-year: A/B.
FAS: patients who were randomized and have received at least one (complete or partial) infusion of the study drug.
SSW: 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 24 weeks.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [51] - FAS [52] - FAS [53] - SSW [54] - SSW [55] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Annualized relapse rate after 48 weeks | ||||||||||||||||||||||||
End point description |
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 per patient. B: Duration of follow-up time per patient,
defined as: (last day of follow-up - day of randomization + 1) / 365.25. Relapses per patient-year: A/B.
FAS: patients who were randomized and have received at least one (complete or partial) infusion of the study drug.
SSW: 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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 48 weeks.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [56] - FAS [57] - FAS, patients who switch from Tysabri to PB006 are excluded. [58] - SSW [59] - SSW [60] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks | ||||||||||||
End point description |
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.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 24.
|
||||||||||||
|
|||||||||||||
Notes [61] - FAS [62] - FAS |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks | ||||||||||||||||||||||||
End point description |
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.
FAS population: patients who were randomized and have received at least one (complete or partial) infusion of the study drug.
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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
FAS: Baseline (week 0) and week 48.
SSW: Baseline (week 24) and week 48.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [63] - FAS [64] - FAS, patients who switch from Tysabri to PB006 are excluded. [65] - SSW [66] - SSW [67] - SSW |
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks | ||||||||||||||||||||||||||||||||||||
End point description |
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.
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 (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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 24 weeks.
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [68] - SAF [69] - SAF [70] - SSW [71] - SSW [72] - SSW |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks | ||||||||||||||||||||||||||||||||||||
End point description |
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.
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 (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.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Up to 48 weeks.
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [73] - SAF [74] - SAF [75] - SSW [76] - SSW [77] - SSW |
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with neutralizing antibodies after 24 weeks | ||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks.
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 (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.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Up to 24 weeks.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [78] - SAF [79] - SAF [80] - SSW [81] - SSW [82] - SSW |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with neutralizing antibodies after 48 weeks | ||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks.
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 (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.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Up to 48 weeks.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [83] - SAF [84] - SAF [85] - SSW [86] - SSW [87] - SSW |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks | |||||||||||||||
End point description |
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks.
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.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to week 24
|
|||||||||||||||
|
||||||||||||||||
Notes [88] - SAF [89] - SAF |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks | ||||||||||||||||||||
End point description |
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks. 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.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Up to 48 weeks.
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [90] - SAF [91] - SAF [92] - SAF |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Natalizumab trough concentration (Ctrough) over time, week 8 | ||||||||||||
End point description |
Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 8
|
||||||||||||
|
|||||||||||||
Notes [93] - FAS [94] - FAS |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Natalizumab trough concentration (Ctrough) over time, week 16 | ||||||||||||
End point description |
Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 16
|
||||||||||||
|
|||||||||||||
Notes [95] - FAS [96] - FAS |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Natalizumab trough concentration (Ctrough) over time, week 24 | ||||||||||||
End point description |
Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Notes [97] - FAS [98] - FAS |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Natalizumab trough concentration (Ctrough) over time, week 32 | ||||||||||||
End point description |
Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 32
|
||||||||||||
|
|||||||||||||
Notes [99] - FAS [100] - FAS, patients who switch from Tysabri to PB006 are excluded. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Natalizumab trough concentration (Ctrough) over time, week 48 | ||||||||||||
End point description |
Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment.
The Full Analysis Set (FAS) population: 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 48
|
||||||||||||
|
|||||||||||||
Notes [101] - FAS [102] - FAS, patients who switch from Tysabri to PB006 are excluded. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of patients without new/enlarging T2-weighted lesions over 24 weeks | ||||||||||||||||||
End point description |
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.
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Week 0 (baseline), week 8, 16, 20 and 24.
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [103] - FAS [104] - FAS [105] - SSW [106] - SSW [107] - SSW |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of patients without new/enlarging T2-weighted lesions over 48 weeks | ||||||||||||||||||
End point description |
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.
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [108] - FAS [109] - FAS, patients who switch from Tysabri to PB006 are excluded. [110] - SSW [111] - SSW [112] - SSW |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal clinical laboratory tests at week 24 and week 48 | ||||||||||||||||||||||||||||||
End point description |
Number of patients with abnormal clinical laboratory tests at week 24 and 48.
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 switched or not.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
At week 24 and week 48.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [113] - FAS [114] - FAS, patients who switch from Tysabri to PB006 are excluded at week 48. [115] - SSW [116] - SSW [117] - SSW |
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of patients with abnormal findings in physical examination at week 24 and week 48 | |||||||||||||||
End point description |
Number of patients with abnormal findings in physical examination at week 24 and week 48.
Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF).
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Week 24 and end of study (week 48).
|
|||||||||||||||
|
||||||||||||||||
Notes [118] - SAF [119] - SAF |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from baseline in blood pressure at week 24 | ||||||||||||||||||
End point description |
Change from baseline in diastolic and systolic blood Pressure at week 24.
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.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
At baseline and week 24.
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [120] - SAF [121] - SAF |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in blood pressure at week 48 | ||||||||||||
End point description |
Change from baseline in diastolic and systolic blood Pressure at week 48.
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At baseline and end of study (week 48).
|
||||||||||||
|
|||||||||||||
Notes [122] - SAF [123] - SAF, patients who switch from Tysabri to PB006 are excluded. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in heart rate at week 24 | ||||||||||||
End point description |
Change from baseline in heart rate at week 24.
Safety Population: Patients who received at least 1 (complete or partial) infusion of the study drug were included in the Safety Population (SAF). Patients in this group were analyzed as treated.
Only subjects with non-missing endpoints were included in the analysis.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At baseline and week 24.
|
||||||||||||
|
|||||||||||||
Notes [124] - SAF [125] - SAF |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in heart rate at week 48 | ||||||||||||
End point description |
Change from baseline in heart rate at week 48.
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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At baseline and end of study (week 48).
|
||||||||||||
|
|||||||||||||
Notes [126] - SAF [127] - SAF, patients who switch from Tysabri to PB006 are excluded. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
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).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
PB006
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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. Included in this arm are subjects who switched from Tysabri to PB006 at week 24, covering the period from week 24 till the end of study (week 48). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tysabri
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
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). Included in this arm are subjects who switched from Tysabri to PB006 at week 24, covering the period from week 0 till week 24. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Sep 2019 |
The section about Overall Study Design has been revised to show that serum samples for anti-drug antibody (ADA) formation testing will now be collected at 2 additional time points: 4 Weeks and 28 Weeks. |
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05 Feb 2020 |
The sections Secondary Objectives, Overall Study Design, Secondary Endpoints, Statistical Methods, Secondary endpoints and Planned Sample Size have been updated to include the new study design of switching a group of patients from Tysabri to PB006 at Week 24 to evaluate and compare the immunogenic profiles of those on Tysabri only with those who switched. |
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15 Jul 2020 |
In order to simplify Clinical Study Reporting, the analysis of the primary endpoint will now be conducted together with all secondary endpoints at the end of the study (at Visit 13, Week 48). The primary endpoint itself (at Visit 7, Week 24) is not changed. Most protocol changes in this amendment relate to this simplification |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |