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The purpose of this study is to determine the safety, tolerability, and pharmacokinetics (PK) after intravenous (IV) administration of ASP2408 manufactured from a new production clone and also following single ascending doses of subcutaneous (SC) injections of the same clinical trial material.
The four doses will be studied in sequential cohorts of 8 subjects each, starting with the IV dose, followed by the subcutaneous doses in ascending order of dose. Within each cohort, subjects will be randomized to either active drug or matching placebo in a 3:1 ratio (6 active and 2 placebo).
All subjects in each arm will be confined for 8 days and followed for a minimum of 90 days up to 9 months if necessary. Subjects who have study drug terminated should remain in the study, if possible and have scheduled procedures and follow-up.
Subjects who have detectable blood levels of ASP2408 after Day 90 will be unblinded and followed monthly until ASP2408 levels are below the limit of quantification. In addition, subjects who have persistent anti-ASP2408 antibodies after Day 90 will be unblinded and followed every 30 (± 3) days for up to 9 months until the level of these antibodies are declining, no longer detectable, and/or have no clinical consequence.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous ASP2408 | Experimental |
| |
| Subcutaneous ASP2408 low dose | Experimental |
| |
| Subcutaneous ASP2408 middle dose | Experimental |
| |
| Subcutaneous ASP2408 high dose | Experimental |
| |
| Intravenous Placebo | Placebo Comparator |
| |
| Subcutaneous Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ASP2408 | Drug | Intravenous (IV) infusion and subcutaneous (SC) injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic parameter of ASP2408: AUClast | Area under the concentration - Time curve from time 0 up to the last quantifiable concentration (AUClast) | Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90 |
| Pharmacokinetic parameter of ASP2408: AUCinf | Area under the concentration - Time curve from time 0 extrapolated to infinity (AUCinf) | Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90 |
| Pharmacokinetic parameter of ASP2408: Cmax | Maximum concentration (Cmax) | Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90 |
| Safety assessed by adverse events (AEs), laboratory tests, immunoglobulin quantification (class), 12-lead electrocardiograms, vital signs and anti-ASP2408 antibody formation | Up to day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of pharmacokinetics of ASP2408: tmax, t 1/2, Vz/F, CL/F and F (%) | Time to attain Cmax (tmax), apparent terminal elimination half-life (t 1/2), apparent volume of distribution (Vz/F), apparent body clearance (CL/F) and absolute bioavailability (F%) | Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90 |
| Pharmacodynamic Profile: CD80 and CD86 receptor occupancy, peripheral lymphocyte subset quantification (leukocyte phenotypes) and total lymphocyte count |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Senior Medical Director | Astellas Pharma Global Development, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel International | Baltimore | Maryland | 21225 | United States |
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| Placebo | Drug | Intravenous (IV) infusion and Subcutaneous (SC) injection |
|
| Days 1-3, 5, 8, 15, 22, 29, 43, 60 and 90 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000626017 | ASP2408 |
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