A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Intravenous Administration of ASP2408 Manufactured From a New Production Clone and Following Single Ascending Doses of Subcutaneous Injections in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Pharmacokinetics of ASP2408
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic parameter of ASP2408: AUClast
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subject weighs at least 50 kg, a maximum of 92.5 kg and has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- •The subject's 12-lead electrocardiogram (ECG) results are normal
- •The female subject must be at least two years postmenopausal OR surgically sterile and not pregnant or lactating
- •The male subject agrees to the use of male condoms until the end of study or 60 days post dose, whichever is longer
Exclusion Criteria
- •The subject has a history of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding adequately-treated non-melanoma skin cancer
- •The subject has a history of severe allergic or anaphylactic reactions
- •The subject is a female of childbearing potential
- •The subject has a history of consuming more than 14 units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within the past 2 years (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits)
- •The subject has a positive test for alcohol or drugs of abuse
- •The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check-in
- •The subject has a past history of opportunistic infection
- •The subject has a supine mean systolic blood pressure \< 90 or \> 160 mmHg and a mean diastolic blood pressure \< 50 or \> 90 mmHg, or mean pulse rate higher than 100 beats per minute (bpm)
- •The subject is known positive for human immunodeficiency virus (HIV) antibody
- •The subject has a positive tuberculosis (TB) skin test, Quantiferon Gold test or T-SPOT® test
Arms & Interventions
Subcutaneous Placebo
Intervention: Placebo
Intravenous Placebo
Intervention: Placebo
Intravenous ASP2408
Intervention: ASP2408
Subcutaneous ASP2408 low dose
Intervention: ASP2408
Subcutaneous ASP2408 middle dose
Intervention: ASP2408
Subcutaneous ASP2408 high dose
Intervention: ASP2408
Outcomes
Primary Outcomes
Pharmacokinetic parameter of ASP2408: AUClast
Time Frame: Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90
Area under the concentration - Time curve from time 0 up to the last quantifiable concentration (AUClast)
Pharmacokinetic parameter of ASP2408: AUCinf
Time Frame: Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90
Area under the concentration - Time curve from time 0 extrapolated to infinity (AUCinf)
Pharmacokinetic parameter of ASP2408: Cmax
Time Frame: Days 1-9, 11, 13, 15, 22, 29, 43, 60, and 90
Maximum concentration (Cmax)
Safety assessed by adverse events (AEs), laboratory tests, immunoglobulin quantification (class), 12-lead electrocardiograms, vital signs and anti-ASP2408 antibody formation
Time Frame: Up to day 90
Secondary Outcomes
- Composite of pharmacokinetics of ASP2408: tmax, t 1/2, Vz/F, CL/F and 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(Days 1-3, 5, 8, 15, 22, 29, 43, 60 and 90)