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

• ClinicalTrials.gov Identifier: NCT04115488
• Recruitment Status: Completed
• First Posted: October 4, 2019
• Results First Posted: July 3, 2023
• Last Update Posted: July 3, 2023
• Sponsor: Polpharma Biologics S.A.
• Information provided by (Responsible Party): Polpharma Biologics S.A.

Tracking Information

• First Submitted Date: September 10, 2019
• First Posted Date: October 4, 2019
• Results First Submitted Date: April 28, 2023
• Results First Posted Date: July 3, 2023
• Last Update Posted Date: July 3, 2023
• Actual Study Start Date: October 1, 2019
• Actual Primary Completion Date: August 23, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2023)

Cumulative Number of New Active Lesions Over 24 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24. ]

Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.

Original Primary Outcome Measures (submitted: October 1, 2019)

Evaluate and compare the cumulative number of new actives lesions [ Time Frame: Change from baseline to Week 24 ]

Brain MRI scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new active lesions" per patient

Current Secondary Outcome Measures (submitted: June 13, 2023)

• Cumulative Number of New Active Lesions Over 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Cumulative number of new active lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent was administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24. ]
  Cumulative number of new GdE T1-weighted lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Cumulative number of new GdE T1-weighted lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24. ]
  Number of patients without new GdE T1-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Number of patients without new GdE T1-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24. ]
  Cumulative number of new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
• Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Cumulative number of new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
• Number of Persistent Lesions After 24 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24. ]
  Number of persistent lesions after 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Number of Persistent Lesions After 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Number of persistent lesions after 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
• Annualized Relapse Rate After 24 Weeks [ Time Frame: Up to 24 weeks. ]
  Annualized relapse rate after 24 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
• Annualized Relapse Rate After 48 Weeks [ Time Frame: Up to 48 weeks. ]
  Annualized relapse rate after 48 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
• Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks [ Time Frame: Baseline and week 24. ]
  Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in multiple sclerosis (MS), is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. After re-randomization, Week 24 is considered baseline.
• Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks [ Time Frame: FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48. ]
  Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in MS, is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists.
• Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks [ Time Frame: Up to 24 weeks. ]
  Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
• Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks [ Time Frame: Up to 48 weeks. ]
  Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
• Percentage of Subjects With Neutralizing Antibodies After 24 Weeks [ Time Frame: Up to 24 weeks. ]
  Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks.
• Percentage of Subjects With Neutralizing Antibodies After 48 Weeks [ Time Frame: Up to 48 weeks. ]
  Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks.
• Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks [ Time Frame: Up to week 24 ]
  Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks.
• Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks [ Time Frame: Up to 48 weeks. ]
  Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks.
• Natalizumab Trough Concentration (Ctrough) Over Time, Week 8 [ Time Frame: Week 8 ]
  Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
• Natalizumab Trough Concentration (Ctrough) Over Time, Week 16 [ Time Frame: Week 16 ]
  Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
• Natalizumab Trough Concentration (Ctrough) Over Time, Week 24 [ Time Frame: Week 24 ]
  Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
• Natalizumab Trough Concentration (Ctrough) Over Time, Week 32 [ Time Frame: Week 32 ]
  Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
• Natalizumab Trough Concentration (Ctrough) Over Time, Week 48 [ Time Frame: Week 48 ]
  Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
• Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks [ Time Frame: Week 0 (baseline), week 8, 16, 20 and 24. ]
  Number of patients without new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
• Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks [ Time Frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48. ]
  Number of patients without new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
• Number of Patients With Abnormal Clinical Laboratory Tests at Week 24 [ Time Frame: At week 24. ]
  Number of patients with abnormal clinical laboratory tests at week 24.
• Number of Patients With Abnormal Clinical Laboratory Tests at Week 48 [ Time Frame: At week 48. ]
  Number of patients with abnormal clinical laboratory tests at week 48.
• Number of Patients With Abnormal Findings in Physical Examination at Week 24 [ Time Frame: Week 24. ]
  Number of patients with abnormal findings in physical examination at week 24.
• Number of Patients With Abnormal Findings in Physical Examination at Week 48 [ Time Frame: End of study (week 48). ]
  Number of patients with abnormal findings in physical examination at week 48.
• Change From Baseline in Blood Pressure at Week 24 [ Time Frame: At baseline and week 24. ]
  Change from baseline in diastolic and systolic blood Pressure at week 24.
• Change From Baseline in Blood Pressure at Week 48 [ Time Frame: At baseline and end of study (week 48). ]
  Change from baseline in diastolic and systolic blood Pressure at week 48.
• Change From Baseline in Heart Rate at Week 24 [ Time Frame: At baseline and week 24. ]
  Change from baseline in heart rate at week 24.
• Change From Baseline in Heart Rate at Week 48 [ Time Frame: At baseline and end of study (week 48). ]
  Change from baseline in heart rate at week 48.

Original Secondary Outcome Measures (submitted: October 1, 2019)

• Evaluate and compare the cumulative number of new active lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new active lesions" per patient
• Evaluate and compare the cumulative number of new gadolinium-enhancing T1-weighted lesions [ Time Frame: Change from baseline to Week 24 ]
  Brain MRI T1-weighted scans with contrast agent done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new gadolinium enhancing T1-weighted lesions" per patient
• Evaluate and compare the cumulative number of new gadolinium-enhancing T1-weighted lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI T1-weighted scans with contrast agent done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new gadolinium enhancing T1-weighted lesions" per patient
• Evaluate and compare the number of patients without new gadolinium-enhancing T1-weighted lesions [ Time Frame: Change from baseline to Week 24 ]
  Brain MRI T1-weighted scans with contrast agent done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of patients without new gadolinium enhancing T1-weighted lesions" per patient
• Evaluate and compare the number of patients without new gadolinium-enhancing T1-weighted lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI T1-weighted scans with contrast agent done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of patients without new gadolinium enhancing T1-weighted lesions" per patient
• Evaluate and compare the cumulative number of new or enlarging T2-weighted lesions [ Time Frame: Change from baseline to Week 24 ]
  Brain MRI T2-weighted scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new or enlarging T2-weighted lesions" per patient
• Evaluate and compare the cumulative number of new or enlarging T2-weighted lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI T2-weighted scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of new or enlarging T2-weighted lesions" per patient
• Evaluate and compare the number of patients without new or enlarging T2-weighted lesions [ Time Frame: Change from baseline to Week 24 ]
  Brain MRI T2-weighted scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of patients with new or enlarging T2-weighted lesions"
• Evaluate and compare the number of patients without new or enlarging T2-weighted lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI T2-weighted scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of patients with new or enlarging T2-weighted lesions"
• Evalueate and compare the number of persistent lesions [ Time Frame: Change from baseline to Week 24 ]
  Brain MRI scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of persistent lesions"
• Evalueate and compare the number of persistent lesions [ Time Frame: Change from baseline to Week 48 ]
  Brain MRI scans done at site for assessing lesions by trained and certified radiology reviewers at MRI central reading center to analyze the "number of persistent lesions"
• Evaluate and compare the annualized relapse rates and changes in Expanded Disability Status Scale (EDSS) [ Time Frame: Change from baseline to Week 24 ]
  Patient assessment through standard neurological examination on 8 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral or mental, other) by rating investigator and documentation as Kurtzke Expanded Disability Status Scale defined as a total score as a numeric value between 0,0 and 10,0
• Evaluate and compare the annualized relapse rates and changes in Expanded Disability Status Scale (EDSS) [ Time Frame: Change from baseline to Week 48 ]
  Patient assessment through standard neurological examination on 8 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral or mental, other) by rating investigator and documentation as Kurtzke Expanded Disability Status Scale defined as a total score as a numeric value between 0,0 and 10,0
• Evaluate and compare local and systemic adverse events and serious adverse events [ Time Frame: Change from baseline to Week 24 ]
  Assessment of adverse events and documentation and grading using common terminology criteria
• Evaluate and compare local and systemic adverse events and serious adverse events [ Time Frame: Change from baseline to Week 48 ]
  Assessment of adverse events and documentation and grading using common terminology criteria
• Evaluate and compare the immunogenic profile (incidence rate of anti-drug (Natalizumab) antibodies and persistent antibodies [ Time Frame: Change from baseline to Week 24 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the presence or absence of anti-Natalizumab antibodies with a validated assay
• Evaluate and compare the immunogenic profile (incidence rate of anti-drug (Natalizumab) antibodies and persistent antibodies [ Time Frame: Change from baseline to Week 48 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the presence or absence of anti-Natalizumab antibodies with a validated assay
• Evaluate and compare Natalizumab trough concentration [ Time Frame: Change from baseline to Week 8 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the Natalizumab trough concentration measured as International Units per litre with a validated assay
• Evaluate and compare Natalizumab trough concentration [ Time Frame: Change from baseline to Week 16 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the Natalizumab trough concentration measured as International Units per litre with a validated assay
• Evaluate and compare Natalizumab trough concentration [ Time Frame: Change from baseline to Week 24 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the Natalizumab trough concentration measured as International Units per litre with a validated assay
• Evaluate and compare Natalizumab trough concentration [ Time Frame: Change from baseline to Week 32 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the Natalizumab trough measured as International Units per litre with a validated assay
• Evaluate and compare Natalizumab trough concentration [ Time Frame: Change from baseline to Week 48 ]
  Serum samples from study participants will be analyzed at a central laboratory to determine the Natalizumab trough concentration measured as International Units per litre with a validated assay
• Evaluate and compare the safety profile by examination of body systems rated as normal or abnormal [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of body systems (injection sites with draining nodes, head/ears/nose/throat, auscultation of lungs, abdominal examination of liver/spleen/lower abdomen, assessment for neurological deficits, musculoskeletal assessment, other observations) rated as normal or abnormal. and analyzed as percentage of patients per treatment arm with abnormal outcomes
• Evaluate and compare the safety profile by examination of body systems rated as normal or abnormal [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of body systems (injection sites with draining nodes, head/ears/nose/throat, auscultation of lungs, abdominal examination of liver/spleen/lower abdomen, assessment for neurological deficits, musculoskeletal assessment, other observations) rated as normal or abnormal. and analyzed as percentage of patients per treatment arm with abnormal outcomes
• Evaluate and compare heart rate, rated as normal or abnormal [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of body temperature in degrees centigrade and analyzed as percentage of patients with normal or abnormal outcomes per treatment arm
• Evaluate and compare heart rate, rated as normal or abnormal [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of body temperature in degrees centigrade and analyzed as percentage of patients with normal or abnormal outcomes per treatment arm
• Evaluate and compare blood pressure, rated as normal or abnormal [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of blood pressure and comprised of systolic blood pressure in mm Hg, diastolic blood pressure in mm Hg rated as normal or abnormal and analyzed as percentage of patients with normal or abnormal outcomes per treatment arm
• Evaluate and compare blood pressure, rated as normal or abnormal [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of blood pressure and comprised of systolic blood pressure in mm Hg, diastolic blood pressure in mm Hg rated as normal or abnormal and analyzed as percentage of patients with normal or abnormal outcomes per treatment arm
• Evaluate and compare body weight [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of body weight in kilograms and analyzed as mean value per treatment arm
• Evaluate and compare body weight [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of body weight in kilograms and analyzed as mean value per treatment arm
• Evaluate and compare body height [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of body height in centimeter and analyzed as mean value per treatment arm
• Evaluate and compare body height [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of body height in centimeter and analyzed as mean value per treatment arm
• Evaluate and compare the safety profile by number of patients with treatment-emergent adverse events [ Time Frame: Change from baseline to Week 24 ]
  Safety profile analyzed as number of patients per treatment group with treatment-emergent adverse events described by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and defined as any adverse event starting or worsening after start of first infusion of investigational medicinal product and summarized by medical dictionary for regulatory activities version 22 by system organ class and preferred term overall, by severity
• Evaluate and compare the safety profile by number of patients with treatment-emergent adverse events [ Time Frame: Change from baseline to Week 48 ]
  Safety profile analyzed as number of patients per treatment group with treatment-emergent adverse events described by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and defined as any adverse event starting or worsening after start of first infusion of investigational medicinal product and summarized by medical dictionary for regulatory activities version 22 by system organ class and preferred term overall, by severity
• Evaluate and compare the safety profile by percentage of patients with treatment-emergent adverse events [ Time Frame: Change from baseline to Week 24 ]
  Safety profile analyzed as percentage of patients per treatment group with treatment-emergent adverse events described by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and defined as any adverse event starting or worsening after start of first infusion of investigational medicinal product and summarized by medical dictionary for regulatory activities version 22 by system organ class and preferred term overall, by severity
• Evaluate and compare the safety profile by percentage of patients with treatment-emergent adverse events [ Time Frame: Change from baseline to Week 48 ]
  Safety profile analyzed as percentage of patients per treatment group with treatment-emergent adverse events described by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 and defined as any adverse event starting or worsening after start of first infusion of investigational medicinal product and summarized by medical dictionary for regulatory activities version 22 by system organ class and preferred term overall, by severity
• Evaluate and compare the safety profile by examination of body systems rated as normal or abnormal [ Time Frame: Change from baseline to Week 24 ]
  Physical examination of body systems (injection sites with draining nodes, head/ears/nose/throat, auscultation of lungs, abdominal examination of liver/spleen/lower abdomen, assessment for neurological deficits, musculoskeletal assessment, other observations) rated as normal or abnormal and analyzed as percentage of patients with abnormal outcomes per treatment arm
• Evaluate and compare the safety profile by examination of body systems rated as normal or abnormal [ Time Frame: Change from baseline to Week 48 ]
  Physical examination of body systems (injection sites with draining nodes, head/ears/nose/throat, auscultation of lungs, abdominal examination of liver/spleen/lower abdomen, assessment for neurological deficits, musculoskeletal assessment, other observations) rated as normal or abnormal and analyzed as percentage of patients with abnormal outcomes per treatment arm

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri®
• Official Title: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
• Brief Summary: This is a multi-center, randomized, parallel arm, double-blind study with a total duration of subjects' participation of 48 weeks. Approximately 260 participants with relapsing-remitting multiple sclerosis will be randomized to receive 12 doses of either PB006 or EU-licensed Natalizumab.

Detailed Description

This is a Phase 3 multicenter, double-blind, active-controlled, randomized, parallel-group study to assess the equivalence in efficacy and similarity in safety of biosimilar PB006 compared to Tysabri in patients with RRMS.

All eligible patients will be randomly assigned to one of two treatment groups in a 1:1 ratio, to receive a total of twelve intravenous (IV) infusion of either PB006 or Tysabri at a dose of 300 mg at each intravenous (IV) infusion administered with every single one intravenous (IV) infusion administered every 4 weeks of either PB006 or Tysabri at a dose of 300 mg starting at visit 1 (week 0) through visit 12 (week 44), for a total of 12 infusions. The End-of-Study Visit (visit 13, week 48) will be performed 4 weeks after the last infusion

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Relapsing-Remitting Multiple Sclerosis (RRMS)

Intervention

Biological: Intravenous (IV) infusions

Intravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses

Study Arms

• Experimental: 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.
  Intervention: Biological: Intravenous (IV) infusions
• Active Comparator: 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).
  Intervention: Biological: Intravenous (IV) infusions

• Publications *: Hemmer B, Wiendl H, Roth K, Wessels H, Hofler J, Hornuss C, Liedert B, Selmaj K. Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial. JAMA Neurol. 2023 Mar 1;80(3):298-307. doi: 10.1001/jamaneurol.2022.5007.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 11, 2022): 265
• Original Estimated Enrollment (submitted: October 1, 2019): 260
• Actual Study Completion Date: February 7, 2022
• Actual Primary Completion Date: August 23, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients (age ≥18 to 60 years), with relapsing-remitting multiple sclerosis (RRMS) defined by the 2010 revised McDonald criteria
• At least 1 documented relapse within the previous year and either ≥1 GdE T1-weighted brain lesions or ≥9 T2-weighted brain lesions at Screening
• Kurtzke Expanded Disability Status Scale (EDSS) score from 0 to 5 (inclusive) at Screening

Exclusion Criteria:

• Manifestation of multiple sclerosis (MS) other than relapsing-remitting multiple sclerosis (RRMS)
• Relapse within the 30 days prior Screening and until administration of the first dose of study drug
• Prior treatment with natalizumab, alemtuzumab, ocrelizumab, daclizumab, rituximab, cladribine, or other B- and T-cell targeting therapies
• Prior total lymphoid irradiation or bone marrow or organ transplantation
• Patients with John Cunningham Virus (JCV) index >1.5 at Screening
• Past or current Progressive Multi-focal leukoencephalopathy (PML) diagnosis
• Severe renal function impairment as defined by serum creatinine values >120 micromol per litre

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Croatia, Georgia, Moldova, Republic of, Poland, Serbia, Ukraine

Administrative Information

• NCT Number: NCT04115488
• Other Study ID Numbers: PB006-03-01
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Polpharma Biologics S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Polpharma Biologics S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Karsten Roth, Dr.; Polpharma Biologics S.A.

• PRS Account: Polpharma Biologics S.A.
• Verification Date: June 2023