Relapsing-Remitting Multiple Sclerosis (RRMS)Phase 3AntelopeNCT04115488
Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri®
A Phase 3 study testing Intravenous (IV) infusions in people with Relapsing-Remitting Multiple Sclerosis (RRMS), run by Polpharma Biologics S.A. at 48 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis (RRMS)
- What is being tested?
- Intravenous (IV) infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 48 sitesin 7 countries
- Study dates
- 1 Oct 2019to 7 Feb 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
48 sites in 7 countries.
48 sites in 7 countries
Ukraine20 sites
Cherkasy Regional Hospital of Cherkasy Oblast Council
Cherkasy
Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital
Dnipro
Ivano-Frankivsk City Clinical Hospital #1
Ivano-Frankivsk
Regional Clinical Hospital
Ivano-Frankivsk
City Clinical Hospital #7
Kharkiv
Institute of Neurology, Psychiatry and Narcology
Kharkiv
Kharkiv Railway Clinical Hospital
Kharkiv
Kyiv City Clinical Hospital
Kyiv
Medical Center of First Private Clinic
Kyiv
National Research Center for Radiation Medicine
Kyiv
Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
Lviv
Lviv City Clinical Hospital #5
Lviv
Center for Reconstructive and Restorative Medicine (University Clinic)
Odesa
Sklifosovskyi Regional Clinical Hospital
Poltava
Ternopil Regional Clinical Psychonevrological Hospital
Ternopil
Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital
Vinnytsia
Clinical Hospital No. 9 under Zaporizhia City Council
Zaporizhia
City Clinical Hospital #2
Zaporizhzhya
Zaporizhia Regional Clinical Hospital
Zaporizhzhya
O.F. Herbachevskyi Regional Clinical Hospital
Zhytomyr, 10008
Belarus6 sites
Grodno Regional Clinical Hospital
Grodno, 230017
Minsk City Clinical Hospital #5
Minsk, 220026
Republican Research and Development Center for Neurology and Neurosurgery
Minsk, 220114
Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
Minsk, 220116
Vitebsk Regional Diagnostic Center
Vitebsk, 210023
Vitebsk Regional Clinical Hospital
Vitebsk, 210037
Georgia6 sites
P. Sarajishvili Institute of Neurology, LTD
Tbilisi, 0112
LTD Saint Michael Archangel Multifunctional Clinical Hospital
Tbilisi, 0159
Malkhaz Katsiashvili Multiprofile Emergency Medicine Center
Tbilisi, 0172
LTD S.Khechinashvili University Hospital
Tbilisi, 0179
LTD Aversi Clinic
Tbilisi
Pineo Medical Ecosystem
Tbilisi
Poland6 sites
COPERNICUS Podmiot Leczniczy Sp. z o.o N. Copernicus Hospital, Department of Neurology
Gdansk, Pomeranian Voivodeship, 80-803
Neuro-Medic
Katowice, 40-555
Neurology Center Krzysztof Selmaj
Lodz, 90-324
Provincial Specialist Hospital in Olsztyn, Department of Neurology
Olsztyn, 10-561
MED-Polonia, Sp. z o.o. (LLC)
Poznan
NeuroProtect Medical Center
Warsaw, 01-684
Serbia4 sites
Clinical Center of Serbia, Clinic of Neurology
Belgrade, 11000
Clinical Hospital Center Zemun, Department of Neurology
Belgrade, 11080
Clinical Center Kragujevac, Clinic of Neurology
Kragujevac, 34000
Clinical Center of Vojvodina, Clinic of Neurology
Novi Sad, 21000
Croatia3 sites
Clinical Hospital Center Osijek, Clinic of Neurology
Osijek, 31000
Clinical Hospital Center Split, Clinic of Neurology
Split, 21000
University Hospital Centre Zagreb, Clinic of Neurology
Zagreb, 10000
Moldova3 sites
Institute for Emergency Medicine, Department of Neurology
Chisinau, 2004
Institute for Emergency Medicine, Department of Neurology
Chisinau, 2028
National Institute of Neurology and Neurosurgery, Vascular Neurology Department
Chisinau, 2028
About this study
Official title: Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
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.
Read the 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
- Being tested
- Intravenous (IV) infusions
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous (IV) infusionsBiological
Intravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses
| Study group | Role | What they receive |
|---|---|---|
| PB006 | Experimental | 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. Receives: Biological: Intravenous (IV) infusions |
| Tysabri | Active comparator | 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). Receives: Biological: Intravenous (IV) infusions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Number of New Active Lesions Over 24 Weeks
Cumulative number of new active lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Measured: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Secondary outcomes (34)
Cumulative Number of New Active Lesions Over 48 Weeks
Cumulative number of new active lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted and new/enlarging T2-weighted lesion. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent was administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks
Cumulative number of new GdE T1-weighted lesions over 24 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks
Cumulative number of new GdE T1-weighted lesions over 48 weeks, calculated as the sum of all new gadolinium-enhancing (GdE) T1-weighted. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks
Number of patients without new GdE T1-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks
Number of patients without new GdE T1-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks
Cumulative number of new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Measured: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks
Cumulative number of new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Number of Persistent Lesions After 24 Weeks
Number of persistent lesions after 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Number of Persistent Lesions After 48 Weeks
Number of persistent lesions after 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of GdE T1-weighted lesions and T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center. A macrocyclic Gd-based contrast agent (gadobutrol, gadoteric acid, or gadoteridol) was to be administered as an Intravenous infusion of 0.1 Millimole per kilogram [mmol/kg].
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Annualized Relapse Rate After 24 Weeks
Annualized relapse rate after 24 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
Measured: Up to 24 weeks.
Annualized Relapse Rate After 48 Weeks
Annualized relapse rate after 48 weeks. Relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality had to be present for at least 24 hours and have occurred in the absence of fever or infection. Annualized relapse rate: A: Number of medically confirmed relapses overall. B: Duration of follow-up time overall, where follow-up time was defined as: (last day of follow-up - day of randomization + 1) / 365.25. The ratio of relapses per patient-year: A/B. Annualized Relapse Rate was calculated across the entire group.
Measured: Up to 48 weeks.
Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks
Change from baseline in Expanded Disability Status Scale (EDSS) after 24 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in multiple sclerosis (MS), is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists. After re-randomization, Week 24 is considered baseline.
Measured: Baseline and week 24.
Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks
Change from baseline in Expanded Disability Status Scale (EDSS) after 48 weeks. The Kurtzke EDSS, commonly used to evaluate the degree of neurologic impairment in MS, is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. Based on a standard neurological examination, the 7 functional systems (plus "other") are rated. These ratings are then used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS. EDSS ratings were performed by independent examining neurologists.
Measured: FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 24 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
Measured: Up to 24 weeks.
Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks
Percentage of subjects with anti-drug (natalizumab) antibodies (ADA) and persistent antibodies after 48 weeks. A positive ADA patient was defined as a patient who had at least 1 positive ADA result in any post-baseline sample. A persistently positive ADA patient was defined as a patient with confirmed positive ADAs in 2 or more consecutive positive ADA samples at post-dose visits.
Measured: Up to 48 weeks.
Percentage of Subjects With Neutralizing Antibodies After 24 Weeks
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 24 weeks.
Measured: Up to 24 weeks.
Percentage of Subjects With Neutralizing Antibodies After 48 Weeks
Percentage of subjects with positive (transient and persistent) neutralizing antibodies after 48 weeks.
Measured: Up to 48 weeks.
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 24 weeks.
Measured: Up to week 24
Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks
Number of subjects with any Treatment-Emergent Adverse Event (TEAE) or any Treatment-Emergent Serious Adverse Event (SAE) after 48 weeks.
Measured: Up to 48 weeks.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 8
Natalizumab trough concentration (Ctrough) over time, week 8. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Measured: Week 8
Natalizumab Trough Concentration (Ctrough) Over Time, Week 16
Natalizumab trough concentration (Ctrough) over time, week 16. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Measured: Week 16
Natalizumab Trough Concentration (Ctrough) Over Time, Week 24
Natalizumab trough concentration (Ctrough) over time, week 24. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Measured: Week 24
Natalizumab Trough Concentration (Ctrough) Over Time, Week 32
Natalizumab trough concentration (Ctrough) over time, week 32. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Measured: Week 32
Natalizumab Trough Concentration (Ctrough) Over Time, Week 48
Natalizumab trough concentration (Ctrough) over time, week 48. Serum samples were collected prior to treatment. Sample was taken prior to treatment for each patient.
Measured: Week 48
Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks
Number of patients without new/enlarging T2-weighted lesions over 24 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Measured: Week 0 (baseline), week 8, 16, 20 and 24.
Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks
Number of patients without new/enlarging T2-weighted lesions over 48 weeks. Assessment of lesions was performed using Magnetic Resonance Imaging (MRI). Identification of T2-weighted lesions was done by a trained and certified radiology reviewer according to standard procedures at the MRI central reading center.
Measured: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Number of Patients With Abnormal Clinical Laboratory Tests at Week 24
Number of patients with abnormal clinical laboratory tests at week 24.
Measured: At week 24.
Number of Patients With Abnormal Clinical Laboratory Tests at Week 48
Number of patients with abnormal clinical laboratory tests at week 48.
Measured: At week 48.
Number of Patients With Abnormal Findings in Physical Examination at Week 24
Number of patients with abnormal findings in physical examination at week 24.
Measured: Week 24.
Number of Patients With Abnormal Findings in Physical Examination at Week 48
Number of patients with abnormal findings in physical examination at week 48.
Measured: End of study (week 48).
Change From Baseline in Blood Pressure at Week 24
Change from baseline in diastolic and systolic blood Pressure at week 24.
Measured: At baseline and week 24.
Change From Baseline in Blood Pressure at Week 48
Change from baseline in diastolic and systolic blood Pressure at week 48.
Measured: At baseline and end of study (week 48).
Change From Baseline in Heart Rate at Week 24
Change from baseline in heart rate at week 24.
Measured: At baseline and week 24.
Change From Baseline in Heart Rate at Week 48
Change from baseline in heart rate at week 48.
Measured: At baseline and end of study (week 48).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start1 Oct 2019
- Primary completion23 Aug 2021
- Study completion7 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsing-Remitting Multiple Sclerosis (RRMS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 265 participants (actual)
Sponsor and investigators
- Lead sponsor
- Polpharma Biologics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Karsten Roth, Dr., Study director, Polpharma Biologics S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04115488
- Sponsor's protocol ID
- PB006-03-01
- Acronym
- Antelope
- Status last verified
- Jun 2023
- First submitted
- 10 Sep 2019
- Last updated
- 3 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 36689214Chamberlain P, Hemmer B, Hofler J, Wessels H, von Richter O, Hornuss C, Poetzl J, Roth K. Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile. Front Immunol. 2024 Dec 19;15:1414304. doi: 10.3389/fimmu.2024.1414304. eCollection 2024.
PubMed 39749348
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of the Biosimilar Natalizumab PB006 in Comparison to Tysabri® in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
- ClinicalTrials.gov ID
- NCT04115488
- Acronym / sponsor ID
- Antelope / PB006-03-01
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 265 participants (actual)
- Lead sponsor
- Polpharma Biologics S.A.Industry (pharma, biotech, devices)
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 23 Aug 2021 (actual)
- Study completion
- 7 Feb 2022 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PB006 | Experimental | Biological: Intravenous (IV) infusionsPatients with relapsing-remitting multiple sclerosis (RRMS) received intravenous (IV) infusions every 4 weeks of PB006 at a dose of 300 milligram (mg) starting at Visit 1 (Week 0) through Visit 12 (Week 44), for a total of 12 infusions. |
| Tysabri | Active comparator | Biological: Intravenous (IV) infusionsPatients 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). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous (IV) infusionsIntravenous (IV) infusions of a dose of 300mg, every 4 weeks with a total of 12 doses | Biological | PB006, Tysabri |
Primary outcome
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.
34 secondary outcomes
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 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 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 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 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 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 48 Weeks
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
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 48 Weeks
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
Annualized Relapse Rate After 24 Weeks
Time frame: Up to 24 weeks.
Annualized Relapse Rate After 48 Weeks
Time frame: Up to 48 weeks.
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 48 Weeks
Time frame: FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.
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 48 Weeks
Time frame: Up to 48 weeks.
Percentage of Subjects With Neutralizing Antibodies After 24 Weeks
Time frame: Up to 24 weeks.
Percentage of Subjects With Neutralizing Antibodies 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 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 48 Weeks
Time frame: Up to 48 weeks.
Natalizumab Trough Concentration (Ctrough) Over Time, Week 8
Time frame: Week 8
Natalizumab Trough Concentration (Ctrough) Over Time, Week 16
Time frame: Week 16
Natalizumab Trough Concentration (Ctrough) Over Time, Week 24
Time frame: Week 24
Natalizumab Trough Concentration (Ctrough) Over Time, Week 32
Time frame: Week 32
Natalizumab Trough Concentration (Ctrough) Over Time, Week 48
Time frame: Week 48
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 48 Weeks
Time frame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
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 48
Time frame: 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 48
Time frame: End of study (week 48).
Change From Baseline in Blood Pressure at Week 24
Time frame: At baseline and 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 Heart Rate at Week 24
Time frame: At baseline and week 24.
Change From Baseline in Heart Rate at Week 48
Time frame: At baseline and end of study (week 48).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36689214Hemmer 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.
- Derived from this study: PubMed 39749348Chamberlain P, Hemmer B, Hofler J, Wessels H, von Richter O, Hornuss C, Poetzl J, Roth K. Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile. Front Immunol. 2024 Dec 19;15:1414304. doi: 10.3389/fimmu.2024.1414304. eCollection 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karsten Roth, Dr. study director
Polpharma Biologics S.A.
48 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous (IV) infusions in people with Relapsing-Remitting Multiple Sclerosis (RRMS), run by Polpharma Biologics S.A. at 48 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in Ukraine, Belarus, Georgia, Poland, Serbia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Number of New Active Lesions Over 24 Weeks (time frame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04115488, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2023.