Multiple Sclerosis MS
Conditions
Interventions
The volunteer will receive PB006, EU approved Tysabri, or US-licensed Tysabri
as an intravenous infusion over 60 minutes. The dose he or she will receive is
3 mg/kg body weight.
Sponsors
Polpharma Biologics S.A.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. The subject is male/female and 18 to 54 years of age, inclusive 2. The subject is healthy as determined by their medical history, a physical examination, vital signs, an ECG and clinical laboratory testing 3. The subject has a BMI within the range of 18.5 to 30.0 kg/m2, inclusive and a body weight of 50 - 92 kg, inclusive 4. The subject provided written, informed consent prior to any clinical study-specific procedures. 5. Male subject (if his female spouse/partner is of childbearing potential) must confirm that he is using two acceptable methods for contraception during the study and for 3 months after final study drug administration. Male subject should confirm he has informed his partner of participation in the study and the need to avoid pregnancy. Surgically sterilised male subjects do not require additional use of contraception. Subject needs, after implementation of amendment 3, 2 negative PCR SARS-CoV-2 tests before dosing with natalizumab (after admission to the clinic and prior to dosing). Further criteria apply
Exclusion criteria
Exclusion criteria: 1. Any known exposure to natalizumab, alemtuzumab, ocrelizumab, daclizumab, rituximab, ofatumumab or obinutuzumab or any other B- and T-cell targeting therapies. 2. Any known exposure to immunosuppressive agents 3. Known or suspected hypersensitivity to natalizumab, or any components of the formulation used 4. Any exposure to steroids prior to dosing, to agents such as interferon-β, glatiramer acetate, fingolimod or laquinimod, to teriflunomide or to dimethyl fumarate 5. Plasma exchange within 3 weeks prior to dosing. Exclusion of subjects with a history or evidence of SARS-CoV-2 infection in the last month prior screening 1 or having been in confirmed contact with SARS-CoV-2 positive subjects in the last 2 weeks before dosing (after implementation of amendment 3). Further criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • To demonstrate pharmacokinetic comparability of PB006 to US-licensed Tysabri® in terms of AUC0-inf of total natalizumab • To demonstrate pharmacokinetic comparability of PB006 to EU-approved Tysabri® in terms of AUC0-inf of total natalizumab • To demonstrate comparability pharmacokinetics of US-licensed and EU-approved Tysabri® in terms of AUC0-inf of total natalizumab • To demonstrate pharmacodynamic comparability of PB006 to pooled reference (US-licensed Tysabri® and EU-approved Tysabri®) in terms of baseline-adjusted AUEC0-12w of CD19+ • To demonstrate pharmacodynamic comparability of PB006 to US-licensed Tysabri® and EU-approved Tysabri® in terms of parameters of a4-integrin receptor saturation | — |
Secondary
| Measure | Time frame |
|---|---|
| • To support pharmacokinetic comparability of PB006 to US-licensed Tysabri® and EU-approved Tysabri® in terms of secondary PK parameters of total natalizumab • To support pharmacokinetic comparability of PB006 to US-licensed Tysabri® and EU-approved Tysabri® in terms of PK parameters of unexchanged natalizumab • To support comparability of PB006 to US-licensed Tysabri® and EU-approved Tysabri® in terms of secondary PD parameters of baseline-adjusted CD19+ • To support pharmacodynamic comparability of PB006 with US-licensed Tysabri® and EU-approved Tysabri® in terms of sVCAM decrease • To support pharmacodynamic comparability of PB006 with US-licensed Tysabri® and EU-approved Tysabri® in terms of sMAdCAM decrease • To support pharmacodynamic comparability of PB006 to US-licensed Tysabri® and EU-approved Tysabri® in terms of PD parameters of CD34+ • To support comparable immunogenicity profiles of PB006 with US-licensed Tysabri® and with EU-approved Tysabri® • To support comparable safety and tolerability profiles of PB006 and both US-licensed Tysabri® and EU-approved Tysabri® | — |
Countries
Netherlands
Outcome results
None listed