Clinical trial NCT04115488: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis (RRMS)
Lead sponsor: Polpharma Biologics S.A.
Sponsor class: INDUSTRY
First posted: 2019-10-04
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Cumulative Number of New Active Lesions Over 24 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
Secondary outcomes:
measure: Cumulative Number of New Active Lesions Over 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
measure: Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
measure: Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
measure: Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Number of Persistent Lesions After 24 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20 and 24.
measure: Number of Persistent Lesions After 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Annualized Relapse Rate After 24 Weeks
timeFrame: Up to 24 weeks.
measure: Annualized Relapse Rate After 48 Weeks
timeFrame: Up to 48 weeks.
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks
timeFrame: Baseline and week 24.
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks
timeFrame: FAS: Baseline (week 0) and week 48. SSW: Baseline (week 24) and week 48.
measure: Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks
timeFrame: Up to 24 weeks.
measure: Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks
timeFrame: Up to 48 weeks.
measure: Percentage of Subjects With Neutralizing Antibodies After 24 Weeks
timeFrame: Up to 24 weeks.
measure: Percentage of Subjects With Neutralizing Antibodies After 48 Weeks
timeFrame: Up to 48 weeks.
measure: Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks
timeFrame: Up to week 24
measure: Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks
timeFrame: Up to 48 weeks.
measure: Natalizumab Trough Concentration (Ctrough) Over Time, Week 8
timeFrame: Week 8
measure: Natalizumab Trough Concentration (Ctrough) Over Time, Week 16
timeFrame: Week 16
measure: Natalizumab Trough Concentration (Ctrough) Over Time, Week 24
timeFrame: Week 24
measure: Natalizumab Trough Concentration (Ctrough) Over Time, Week 32
timeFrame: Week 32
measure: Natalizumab Trough Concentration (Ctrough) Over Time, Week 48
timeFrame: Week 48
measure: Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks
timeFrame: Week 0 (baseline), week 8, 16, 20 and 24.
measure: Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks
timeFrame: Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.
measure: Number of Patients With Abnormal Clinical Laboratory Tests at Week 24
timeFrame: At week 24.
measure: Number of Patients With Abnormal Clinical Laboratory Tests at Week 48
timeFrame: At week 48.
measure: Number of Patients With Abnormal Findings in Physical Examination at Week 24
timeFrame: Week 24.
measure: Number of Patients With Abnormal Findings in Physical Examination at Week 48
timeFrame: End of study (week 48).
measure: Change From Baseline in Blood Pressure at Week 24
timeFrame: At baseline and week 24.
measure: Change From Baseline in Blood Pressure at Week 48
timeFrame: At baseline and end of study (week 48).
measure: Change From Baseline in Heart Rate at Week 24
timeFrame: At baseline and week 24.
measure: Change From Baseline in Heart Rate at Week 48
timeFrame: At baseline and end of study (week 48).
Other outcomes:
Locations:
city: Grodno
country: Belarus
facility: Grodno Regional Clinical Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Hospital #5
city: Minsk
country: Belarus
facility: Republican Research and Development Center for Neurology and Neurosurgery
city: Minsk
country: Belarus
facility: Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Diagnostic Center
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Osijek
country: Croatia
facility: Clinical Hospital Center Osijek, Clinic of Neurology
city: Split
country: Croatia
facility: Clinical Hospital Center Split, Clinic of Neurology
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb, Clinic of Neurology
city: Tbilisi
country: Georgia
facility: P. Sarajishvili Institute of Neurology, LTD
city: Tbilisi
country: Georgia
facility: LTD Saint Michael Archangel Multifunctional Clinical Hospital
city: Tbilisi
country: Georgia
facility: Malkhaz Katsiashvili Multiprofile Emergency Medicine Center
city: Tbilisi
country: Georgia
facility: LTD S.Khechinashvili University Hospital
city: Tbilisi
country: Georgia
facility: LTD Aversi Clinic
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem
city: Chisinau
country: Moldova, Republic of
facility: Institute for Emergency Medicine, Department of Neurology
city: Chisinau
country: Moldova, Republic of
facility: Institute for Emergency Medicine, Department of Neurology
city: Chisinau
country: Moldova, Republic of
facility: National Institute of Neurology and Neurosurgery, Vascular Neurology Department
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o.o N. Copernicus Hospital, Department of Neurology
state: Pomerania
city: Katowice
country: Poland
facility: Neuro-Medic
city: Lodz
country: Poland
facility: Neurology Center Krzysztof Selmaj
city: Olsztyn
country: Poland
facility: Provincial Specialist Hospital in Olsztyn, Department of Neurology
city: Poznan
country: Poland
facility: MED-Polonia, Sp. z o.o. (LLC)
city: Warszawa
country: Poland
facility: NeuroProtect Medical Center
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic of Neurology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun, Department of Neurology
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac, Clinic of Neurology
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina, Clinic of Neurology
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Hospital of Cherkasy Oblast Council
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankivsk City Clinical Hospital #1
city: Ivano-Frankivs'k
country: Ukraine
facility: Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: City Clinical Hospital #7
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology
city: Kharkiv
country: Ukraine
facility: Kharkiv Railway Clinical Hospital
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital
city: Kyiv
country: Ukraine
facility: Medical Center of First Private Clinic
city: Kyiv
country: Ukraine
facility: National Research Center for Radiation Medicine
city: Lviv
country: Ukraine
facility: Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
city: Lviv
country: Ukraine
facility: Lviv City Clinical Hospital #5
city: Odesa
country: Ukraine
facility: Center for Reconstructive and Restorative Medicine (University Clinic)
city: Poltava
country: Ukraine
facility: Sklifosovskyi Regional Clinical Hospital
city: Ternopil'
country: Ukraine
facility: Ternopil Regional Clinical Psychonevrological Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital
city: Zaporizhia
country: Ukraine
facility: Clinical Hospital No. 9 under Zaporizhia City Council
city: Zaporizhzhya
country: Ukraine
facility: City Clinical Hospital #2
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhia Regional Clinical Hospital
city: Zhytomyr
country: Ukraine
facility: O.F. Herbachevskyi Regional Clinical Hospital
Study officials:
affiliation: Polpharma Biologics S.A.
name: Karsten Roth, Dr.
role: STUDY_DIRECTOR
References:
citation: 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.