A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
Overview
- Phase
- Phase 1
- Intervention
- ASP2409
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 58
- Locations
- 10
- Primary Endpoint
- Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of single, ascending, intravenous (IV) doses of ASP2409 in patients with Rheumatoid Arthritis (RA) on methotrexate (MTX) and to evaluate the pharmacodynamics (PD) of ASP2409.
Detailed Description
This is a dose-escalation study. Sequential cohorts of subjects will receive increasing doses of ASP2409 or matching placebo. Subjects in all cohorts will stay confined in the unit for 3 days. All subjects will have scheduled outpatient visits and be followed for a minimum of 90 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject weighs at least 50 kg.
- •Subject has a body mass index (BMI) of ≤ 35 kg/m
- •Subject's 12-lead electrocardiogram (ECG) results are normal at Screening and Day -1 or, if abnormal, the abnormality is not clinically significant
- •Female subject must be either:
- •Of non-childbearing potential:
- •post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
- •documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening).
- •Or, if of childbearing potential:
- •must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -
- •must use two forms of birth control (at least one of which must be a barrier method) starting at Screening and throughout the Treatment and Observation Period, and for ≥ 120 days after final study drug administration.
Exclusion Criteria
- •Subject has an ongoing clinically significant systemic disease such as uncompensated heart failure, uncontrolled diabetes mellitus, severe hepatic failure or severe pulmonary disease.
- •Subject has a history of any malignancy except for adequately-treated, non-melanoma skin cancer and adequately-treated in-situ cervical cancer.
- •Subject has a history of severe allergic or anaphylactic reactions.
- •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 past 6 months prior to Screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).
- •Subject has a positive test for alcohol or drugs of abuse (excluding drugs prescribed to subject) at Screening or Day -
- •Subject has/had a viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to Day -
- •Subject has a past history of serious opportunistic infection.
- •Subject is known positive for human immunodeficiency virus (HIV) antibody.
- •Subject has a positive tuberculosis (TB) skin test or Quantiferon Gold test at Screening.
- •Subject has a positive test for hepatitis C antibody, or positive test for hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody at Screening.
Arms & Interventions
ASP2409 Dose Escalation
Intervention: ASP2409
Placebo Dose Escalation
Intervention: Placebo
Outcomes
Primary Outcomes
Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)
Time Frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Safety assessed by laboratory tests
Time Frame: Up to 1 year
Safety assessed by adverse events
Time Frame: Up to 1 year
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf)
Time Frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Safety assessed by physical examinations
Time Frame: Up to 1 year
Safety assessed by vital signs
Time Frame: Up to 1 year
Safety assessed by anti-ASP2409 antibody formation
Time Frame: Up to 1 year
Safety assessed by electrocardiograms (ECGs)
Time Frame: Up to 1 year
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast)
Time Frame: Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
Secondary Outcomes
- Composite of pharmacokinetics of ASP2409 concentration: tmax, t1/2, Vz, Vss, CLtot(Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120)
- Pharmacodynamics of ASP2409: CD86 receptor occupancy(Days 1-3, Days 5, 8, 15, 22, 29, 43, 60, and 90)