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

NCT04115488 | Completed Phase 3 Results FDA Drug

• 1 other identifier: PB006-03-01
• Study Type: interventional
• Target: 265
• Locations: 7 countries
• Sites: 48

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.

Conditions

Relapsing-Remitting Multiple Sclerosis (RRMS)

Outcome Measures

Primary Outcomes (1)

• 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.

  Scans performed at week 0 (baseline), week 8, 16, 20 and 24.

Secondary Outcomes (34)

• Cumulative Number of New Active Lesions Over 48 Weeks

  Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.

• Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks

  Scans performed at week 0 (baseline), week 8, 16, 20 and 24.

• Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks

  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

  Scans performed at week 0 (baseline), week 8, 16, 20 and 24.

• Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks

  Scans performed at week 0 (baseline), week 8, 16, 20, 24 and 48.

Study Arms (2)

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.

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).

Biological: Intravenous (IV) infusions

Interventions

Intravenous (IV) infusions BIOLOGICAL

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

PB006; Tysabri

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Polpharma Biologics S.A.: lead

Study Sites (48)

Grodno Regional Clinical Hospital

Grodno, 230017, Belarus

Location

Minsk City Clinical Hospital #5

Minsk, 220026, Belarus

Location

Republican Research and Development Center for Neurology and Neurosurgery

Minsk, 220114, Belarus

Location

Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology

Minsk, 220116, Belarus

Location

Vitebsk Regional Diagnostic Center

Vitebsk, 210023, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, 210037, Belarus

Location

Clinical Hospital Center Osijek, Clinic of Neurology

Osijek, 31000, Croatia

Location

Clinical Hospital Center Split, Clinic of Neurology

Split, 21000, Croatia

Location

University Hospital Centre Zagreb, Clinic of Neurology

Zagreb, 10000, Croatia

Location

P. Sarajishvili Institute of Neurology, LTD

Tbilisi, 0112, Georgia

Location

LTD Saint Michael Archangel Multifunctional Clinical Hospital

Tbilisi, 0159, Georgia

Location

Malkhaz Katsiashvili Multiprofile Emergency Medicine Center

Tbilisi, 0172, Georgia

Location

LTD S.Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

LTD Aversi Clinic

Tbilisi, Georgia

Location

Pineo Medical Ecosystem

Tbilisi, Georgia

Location

Institute for Emergency Medicine, Department of Neurology

Chisinau, 2004, Moldova

Location

Institute for Emergency Medicine, Department of Neurology

Chisinau, 2028, Moldova

Location

National Institute of Neurology and Neurosurgery, Vascular Neurology Department

Chisinau, 2028, Moldova

Location

COPERNICUS Podmiot Leczniczy Sp. z o.o N. Copernicus Hospital, Department of Neurology

Gdansk, Pomeranian Voivodeship, 80-803, Poland

Location

Neuro-Medic

Katowice, 40-555, Poland

Location

Neurology Center Krzysztof Selmaj

Lodz, 90-324, Poland

Location

Provincial Specialist Hospital in Olsztyn, Department of Neurology

Olsztyn, 10-561, Poland

Location

MED-Polonia, Sp. z o.o. (LLC)

Poznan, Poland

Location

NeuroProtect Medical Center

Warsaw, 01-684, Poland

Location

Clinical Center of Serbia, Clinic of Neurology

Belgrade, 11000, Serbia

Location

Clinical Hospital Center Zemun, Department of Neurology

Belgrade, 11080, Serbia

Location

Clinical Center Kragujevac, Clinic of Neurology

Kragujevac, 34000, Serbia

Location

Clinical Center of Vojvodina, Clinic of Neurology

Novi Sad, 21000, Serbia

Location

Cherkasy Regional Hospital of Cherkasy Oblast Council

Cherkasy, Ukraine

Location

Dnipropetrovsk I.I. Mechnykov Regional Clinical Hospital

Dnipro, Ukraine

Location

Ivano-Frankivsk City Clinical Hospital #1

Ivano-Frankivsk, Ukraine

Location

Regional Clinical Hospital

Ivano-Frankivsk, Ukraine

Location

City Clinical Hospital #7

Kharkiv, Ukraine

Location

Institute of Neurology, Psychiatry and Narcology

Kharkiv, Ukraine

Location

Kharkiv Railway Clinical Hospital

Kharkiv, Ukraine

Location

Kyiv City Clinical Hospital

Kyiv, Ukraine

Location

Medical Center of First Private Clinic

Kyiv, Ukraine

Location

National Research Center for Radiation Medicine

Kyiv, Ukraine

Location

Communal Noncommercial Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

Lviv, Ukraine

Location

Lviv City Clinical Hospital #5

Lviv, Ukraine

Location

Center for Reconstructive and Restorative Medicine (University Clinic)

Odesa, Ukraine

Location

Sklifosovskyi Regional Clinical Hospital

Poltava, Ukraine

Location

Ternopil Regional Clinical Psychonevrological Hospital

Ternopil, Ukraine

Location

Vinnytsia O.I. Yushchenko Regional Psychoneurology Hospital

Vinnytsia, Ukraine

Location

Clinical Hospital No. 9 under Zaporizhia City Council

Zaporizhia, Ukraine

Location

City Clinical Hospital #2

Zaporizhzhya, Ukraine

Location

Zaporizhia Regional Clinical Hospital

Zaporizhzhya, Ukraine

Location

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, 10008, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 36689214 RESULT

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Director Clinical Research and Development
• Organization: Polpharma Biologics S.A.

clinicaltrials@polpharmabiologics.com

+48 607 697 896

Study Officials

• Karsten Roth, Dr.

  Polpharma Biologics S.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: October 4, 2019
• Study Start: October 1, 2019
• Primary Completion: August 23, 2021
• Study Completion: February 7, 2022
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

UA (20); GE (6); CR (3); BE (6); MO (3); PL (6); SE (4)