Phase 3 N=264 Randomized Quadruple-blind Treatment

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

Relapsing-Remitting Multiple Sclerosis (RRMS)

Bottom Line

View on ClinicalTrials.gov: NCT04115488 ↗

Enrolled (actual)

264

Serious AEs

1.7%

Results posted

Jul 2023

Primary outcome: Primary: Cumulative Number of New Active Lesions Over 24 Weeks — 1.4; 1.9; 1.4; 2.1 lesions

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Intravenous (IV) infusions (Biological)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Polpharma Biologics S.A.
Primary completion: Aug 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Cumulative Number of New Active Lesions Over 24 Weeks	1.4; 1.9; 1.4; 2.1; 1.9	—
SECONDARY Cumulative Number of New Active Lesions Over 48 Weeks	1.5; 2.3; 1.5; 2.1; 2.3	—
SECONDARY Cumulative Number of New GdE T1-weighted Lesions Over 24 Weeks	0.3; 0.4; 0.3; 0.4; 0.4	—
SECONDARY Cumulative Number of New GdE T1-weighted Lesions Over 48 Weeks	0.3; 0.4; 0.3; 0.4; 0.4	—
SECONDARY Number of Patients Without New GdE T1-weighted Lesions Over 24 Weeks	109; 105; 105; 23; 80	—
SECONDARY Number of Patients Without New GdE T1-weighted Lesions Over 48 Weeks	105; 80; 102; 22; 79	—
SECONDARY Cumulative Number of New/Enlarging T2-weighted Lesions Over 24 Weeks	1.5; 2.0; 1.5; 2.2; 2.0	—
SECONDARY Cumulative Number of New/Enlarging T2-weighted Lesions Over 48 Weeks	1.6; 2.4; 1.6; 2.2; 2.5	—
SECONDARY Number of Persistent Lesions After 24 Weeks	0.5; 0.4; 0.5; 0.1; 0.6	—
SECONDARY Number of Persistent Lesions After 48 Weeks	0.5; 0.6; 0.5; 0.1; 0.6	—
SECONDARY Annualized Relapse Rate After 24 Weeks	0.206; 0.152; 0.194; 0.143; 0.114	—
SECONDARY Annualized Relapse Rate After 48 Weeks	0.174; 0.133; 0.168; 0.146; 0.113	—
SECONDARY Change From Baseline in Expanded Disability Status Scale (EDSS) After 24 Weeks	-0.03; 0.00	—
SECONDARY Change From Baseline in Expanded Disability Status Scale (EDSS) After 48 Weeks	-0.14; -0.05; -0.10; -0.03; -0.02	—
SECONDARY Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 24 Weeks	28.7; 27.2; 28.7; 43.3; 22.1; 30.3	—
SECONDARY Percentage of Subjects With Anti-drug (Natalizumab) Antibodies (ADA) and Persistent Antibodies After 48 Weeks	10.4; 11.6; 10.4; 17.9; 9.7; 11.3	—
SECONDARY Percentage of Subjects With Neutralizing Antibodies After 24 Weeks	67.6; 64.9; 67.6; 61.5; 66.7	—
SECONDARY Percentage of Subjects With Neutralizing Antibodies After 48 Weeks	61.5; 50.0; 61.5; 60.0; 44.4	—
SECONDARY Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 24 Weeks	62; 64; 1; 0	—
SECONDARY Number of Subjects With Any Treatment-Emergent Adverse Event (TEAE) or Any Treatment-Emergent Serious Adverse Event (SAE) After 48 Weeks	85; 22; 71; 3; 0; 2	—
SECONDARY Natalizumab Trough Concentration (Ctrough) Over Time, Week 8	26804.75; 25010.49	—
SECONDARY Natalizumab Trough Concentration (Ctrough) Over Time, Week 16	33872.92; 32543.28	—
SECONDARY Natalizumab Trough Concentration (Ctrough) Over Time, Week 24	36853.93; 35617.65	—
SECONDARY Natalizumab Trough Concentration (Ctrough) Over Time, Week 32	37450.04; 36865.81	—
SECONDARY Natalizumab Trough Concentration (Ctrough) Over Time, Week 48	39097.58; 38432.86	—
SECONDARY Number of Patients Without New/Enlarging T2-weighted Lesions Over 24 Weeks	75; 72; 72; 18; 52	—
SECONDARY Number of Patients Without New/Enlarging T2-weighted Lesions Over 48 Weeks	71; 52; 69; 17; 51	—
SECONDARY Number of Patients With Abnormal Clinical Laboratory Tests at Week 24	116; 114	—
SECONDARY Number of Patients With Abnormal Clinical Laboratory Tests at Week 48	108; 26; 88	—
SECONDARY Number of Patients With Abnormal Findings in Physical Examination at Week 24	10; 12	—
SECONDARY Number of Patients With Abnormal Findings in Physical Examination at Week 48	11; 10; 11; 3; 7	—
SECONDARY Change From Baseline in Blood Pressure at Week 24	-2.2; -0.6; -1.0; -1.5	—
SECONDARY Change From Baseline in Blood Pressure at Week 48	1.0; 1.8; 0.8; 1.7; 2.4; 3.0	—
SECONDARY Change From Baseline in Heart Rate at Week 24	-0.4; -1.4	—
SECONDARY Change From Baseline in Heart Rate at Week 48	0.8; 1.7; 1.1	—

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.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04115488). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.