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Trial record 1 of 1 for:    PB006
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Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® (Antelope)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04115488
Recruitment Status : Active, not recruiting
First Posted : October 4, 2019
Last Update Posted : August 24, 2020
Sponsor:
Information provided by (Responsible Party):
Polpharma Biologics S.A.

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.

Condition or disease Intervention/treatment Phase
Relapsing-Remitting Multiple Sclerosis (RRMS) Biological: Intravenous (IV) infusions Phase 3

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 administereds 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab

Arm Intervention/treatment
Experimental: Biosimilar Natalizumab, solution for infusion
Biological: Biosimilar (INN: Natalizumab), 15 milliliter solution for infusion in a vial at a concentration of 20 milligrams per milliliter and a total dose of 300 milligrams, for intravenous (IV) infusions after dilution with 100 milliliter sodium chloride solution at a concentration of 0,9 percent, concentration of solution for infusion will be 2,61 milligrams per milliliter, total volume of solution for infusion will be 115 milliliter, a total of 12 doses of 300mg each will be administered every 4 weeks, duration of each infusion is 1 hour at a rate of 2 milliliters per minute
Biological: Intravenous (IV) infusions
Intravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses

Active Comparator: EU licensed Natalizumab ("Tysabri®")
Biological, EU licensed Natalizumab (INN), (tradename "Tysabri®"), 15 milliliter solution for infusion in a vial at a concentration of 20 milligrams per milliliter and a total dose of 300 milligrams, for intravenous (IV) infusions after dilution with 100 milliliter sodium chloride solution at a concentration of 0,9 percent, concentration of solution for infusion will be 2,61 milligrams per milliliter, total volume of solution for infusion will be 115 milliliter, a total of 12 doses of 300mg each will be administered every 4 weeks, duration of each infusion is 1 hour at a rate of 2 milliliters per minute
Biological: Intravenous (IV) infusions
Intravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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"

  9. 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"

  10. 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"

  11. 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"

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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


  24. 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


  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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-fokal Leukencephalopathy (PML) diagnosis
  • Severe renal function impairment as defined by serum creatinine values >120 micromol per litre

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04115488


Locations
Show Show 48 study locations
Sponsors and Collaborators
Polpharma Biologics S.A.
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Responsible Party: Polpharma Biologics S.A.
ClinicalTrials.gov Identifier: NCT04115488    
Other Study ID Numbers: PB006-03-01
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: August 24, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases