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NCT04115488: Antelope

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

Completed Phase 3 Results posted Last updated 3 July 2023
What this trial tests

Phase 3 trial testing Intravenous (IV) infusions in Relapsing-Remitting Multiple Sclerosis (RRMS) in 265 participants. Completed in 7 February 2022.

Timeline
1 October 2019
Primary endpoint
23 August 2021
7 February 2022

Quick facts

Lead sponsorPolpharma Biologics S.A.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment265
Start date1 October 2019
Primary completion23 August 2021
Estimated completion7 February 2022
Sites48 locations across Georgia, Ukraine, Serbia, Poland, Moldova, Belarus, Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Polpharma Biologics S.A. — full company profile →

Who can join

Adults 18 to 60, any sex, with Relapsing-Remitting Multiple Sclerosis (RRMS). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cumulative Number of New Active Lesions Over 24 Weeks Primary · 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.

GroupValue95% CI
PB006 (Per-Protocol)1.4± 3.73
Tysabri (Per-Protocol)1.9± 3.97
PB006 (Safety-Switch)1.4± 3.65
Tysabri Switched to PB006 at Week 24 (Safety-Switch)2.1± 3.78
Tysabri Continued at Week 24 (Safety-Switch)1.9± 4.09
Cumulative Number of New Active Lesions Over 48 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)1.5± 3.72
Tysabri (Full Analysis Set)2.3± 5.68
PB006 (Safety-Switch)1.5± 3.75
Tysabri Switched to PB006 at Week 24 (Safety-Switch)2.1± 3.82
Tysabri Continued at Week 24 (Safety-Switch)2.3± 5.70
Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)0.3± 1.01
Tysabri (Full Analysis Set)0.4± 1.25
PB006 (Safety-Switch)0.3± 1.02
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.4± 0.81
Tysabri Continued at Week 24 (Safety-Switch)0.4± 1.37
Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)0.3± 1.02
Tysabri (Full Analysis Set)0.4± 1.39
PB006 (Safety-Switch)0.3± 1.03
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.4± 0.82
Tysabri Continued at Week 24 (Safety-Switch)0.4± 1.40
Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)109
Tysabri (Full Analysis Set)105
PB006 (Safety-Switch)105
Tysabri Switched to PB006 at Week 24 (Safety-Switch)23
Tysabri Continued at Week 24 (Safety-Switch)80
Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)105
Tysabri (Full Analysis Set)80
PB006 (Safety-Switch)102
Tysabri Switched to PB006 at Week 24 (Safety-Switch)22
Tysabri Continued at Week 24 (Safety-Switch)79
Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks Secondary · 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.

GroupValue95% CI
PB006 (Full Analysis Set)1.5± 3.79
Tysabri (Full Analysis Set)2.0± 4.12
PB006 (Safety-Switch)1.5± 3.83
Tysabri Switched to PB006 at Week 24 (Safety-Switch)2.2± 3.84
Tysabri Continued at Week 24 (Safety-Switch)2.0± 4.25
Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks Secondary · 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.

GroupValue95% CI
PB006 (Full Analysis Set)1.6± 3.09
Tysabri (Full Analysis Set)2.4± 5.79
PB006 (Safety-Switch)1.6± 3.93
Tysabri Switched to PB006 at Week 24 (Safety-Switch)2.2± 3.89
Tysabri Continued at Week 24 (Safety-Switch)2.5± 5.81
Number of Persistent Lesions After 24 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)0.5± 2.46
Tysabri (Full Analysis Set)0.4± 2.92
PB006 (Safety-Switch)0.5± 2.49
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.1± 0.31
Tysabri Continued at Week 24 (Safety-Switch)0.6± 3.37
Number of Persistent Lesions After 48 Weeks Secondary · 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 \[mmol/kg\].

GroupValue95% CI
PB006 (Full Analysis Set)0.5± 2.55
Tysabri (Full Analysis Set)0.6± 3.35
PB006 (Safety-Switch)0.5± 2.58
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.1± 0.26
Tysabri Continued at Week 24 (Safety-Switch)0.6± 3.37
Annualized Relapse Rate After 24 Weeks Secondary · 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) /

GroupValue95% CI
PB006 (Full Analysis Set)0.206
Tysabri (Full Analysis Set)0.152
PB006 (Safety-Switch)0.194
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.143
Tysabri Continued at Week 24 (Safety-Switch)0.114
Annualized Relapse Rate After 48 Weeks Secondary · 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) /

GroupValue95% CI
PB006 (Full Analysis Set)0.174
Tysabri (Full Analysis Set)0.133
PB006 (Safety-Switch)0.168
Tysabri Switched to PB006 at Week 24 (Safety-Switch)0.146
Tysabri Continued at Week 24 (Safety-Switch)0.113

Adverse events — posted to ClinicalTrials.gov

Time frame: From first infusion till the last + 4 weeks, up to 48 weeks. Deaths (all causes): From first infusion till the last (at Week 44) + 24 ± 2 weeks, up to 68 ± 2 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PB006
Serious: 3/161 (2%)
Deaths: 0/161
Tysabri
Serious: 2/133 (2%)
Deaths: 0/133

Serious adverse events (5 terms)

ReactionSystemPB006Tysabri
HypotensionVascular disorders
TremorNervous system disorders
Nasal septum deviationRespiratory, thoracic and mediastinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PneumoniaInfections and infestations
Other adverse events (152 terms — click to expand)

ReactionSystemPB006Tysabri
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
COVID-19Infections and infestations
Back painMusculoskeletal and connective tissue disorders
AstheniaGeneral disorders
FatigueGeneral disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
DepressionPsychiatric disorders
InsomniaPsychiatric disorders
Weight decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
PharyngitisInfections and infestations
DizzinessNervous system disorders
HypoaesthesiaNervous system disorders
ConstipationGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
BronchitisInfections and infestations
HyperthermiaGeneral disorders
Feeling hotGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood pressure increasedInvestigations
C-reactive protein increasedInvestigations
ContusionInjury, poisoning and procedural complications
PresyncopeNervous system disorders
Tension headacheNervous system disorders
VomitingGastrointestinal disorders
HyperbilirubinaemiaHepatobiliary disorders
UrticariaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
LeukocyturiaRenal and urinary disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders
Respiratory tract infectionInfections and infestations

Most-reported serious reactions: Hypotension, Tremor, Nasal septum deviation, Pain in extremity, Pneumonia.

Data from ClinicalTrials.gov NCT04115488 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting integrin pathways: mechanisms and advances in therapy.
    Pang X, He X, Qiu Z, Zhang H, et al · · 2023 · cited 704× · PMID 36588107 · DOI 10.1038/s41392-022-01259-6
  2. Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial.
    Hemmer B, Wiendl H, Roth K, Wessels H, et al · · 2023 · cited 22× · PMID 36689214 · DOI 10.1001/jamaneurol.2022.5007
  3. Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.
    Chao Z, Mei Q, Yang C, Luo J, et al · · 2025 · cited 10× · PMID 40784895 · DOI 10.1038/s41392-025-02332-6
  4. Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab.
    Selmaj K, Roth K, Höfler J, Vitzithum K, et al · · 2024 · cited 7× · PMID 39343860 · DOI 10.1007/s40259-024-00671-4
  5. Targeting Integrin α3 Blocks β1 Maturation, Triggers Endoplasmic Reticulum Stress, and Sensitizes Glioblastoma Cells to TRAIL-Mediated Apoptosis.
    Kuranaga Y, Yu B, Osuka S, Zhang H, et al · · 2024 · cited 3× · PMID 38727288 · DOI 10.3390/cells13090753
  6. Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile.
    Chamberlain P, Hemmer B, Höfler J, Wessels H, et al · · 2024 · cited 1× · PMID 39749348 · DOI 10.3389/fimmu.2024.1414304
  7. Adult and pediatric relapsing multiple sclerosis phase II and phase III trial design and their primary end points: A systematic review.
    Hiramatsu K, Maeda H. · · 2024 · cited 1× · PMID 38708586 · DOI 10.1111/cts.13794

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing