A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Study To Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of ASP2408 After Subcutaneous Injections in Patients With Rheumatoid Arthritis on Methotrexate
Overview
- Phase
- Phase 1
- Intervention
- ASP2408
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 24
- Locations
- 3
- Primary Endpoint
- Pharmacokinetic parameter of ASP2408: AUCtau
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics (PK) of two dosing regimens of multiple, subcutaneous (sc) injections of ASP2408 in patients with Rheumatoid Arthritis (RA) on Methotrexate (MTX) and to evaluate the pharmacodynamics (PD) of ASP2408.
Detailed Description
This is an ascending dose frequency study. There are two cohorts of active and placebo patients. The first cohort is dosed every 4 weeks for a total of 3 doses. The second cohort is dosed every two weeks for a total of 3 doses.
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 prior to study drug dosing or, if abnormal, the abnormality is not clinically significant as determined by the Investigator.
- •Subject has Rheumatoid Arthritis (RA) that was diagnosed according to the 1987 revised criteria of the American College of Rheumatology (ACR) ≥ 6 months prior to Screening.
- •Subject meets the ACR 1991 revised criteria for Global Functional Status in RA, Class I, II or III at Screening.
- •Subject MUST be on concomitant methotrexate (MTX):
- •for ≥ 3 months prior to Day 1, AND
- •at a stable dose (10 - 25 mg/week) for ≥ 28 days prior to Day 1 and throughout the study.
- •Subject's other related medications taken for the treatment of RA at the time of Screening must meet the noted stability requirements and remain on a stable regimen, as follows:
- •Non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxy-genase-2 (COX-2) inhibitors, oral corticosteroids (≤ 10 mg of prednisone, or equivalent, daily) or low dose opioids (≤ 30 mg of oral morphine, or equivalent, daily) must be stable for ≥ 28 days prior to Screening and remain so throughout the Treatment and Observation Period.
Exclusion Criteria
- •Subject has an ongoing infection or has had an infection requiring intravenous antibiotics within 1 month prior to Day
- •Subject has a past history of serious opportunistic infection.
- •Subject has a positive Mantoux tuberculin skin or QuantiFERON-TB Gold test within 90 days of, or at Screening, and has not completed an adequate course of antimicrobial therapy per CDC guidelines.
- •Subject received any live or live-attenuated vaccine within 30 days prior to Day
- •Subject received any of the following:
- •Anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 60 days prior to Day
- •Rituximab (Rituxan®) or any other anti-CD20 antibody within 180 days prior to Day
- •Leflunomide (Arava®) within 60 days prior to drug dosing on Day 1, unless the subject has undergone cholestyramine washout at least 30 days prior to Day
- •Oral or injectable gold, azathioprine, penicillamine, cyclosporine, or tacrolimus within 30 days prior to Day
- •Cyclophosphamide within 180 days prior to Day
Arms & Interventions
ASP2408 low dosing frequency
Intervention: ASP2408
ASP2408 high dosing frequency
Intervention: ASP2408
Placebo low dosing frequency
Intervention: Placebo
Placebo high dosing frequency
Intervention: Placebo
Outcomes
Primary Outcomes
Pharmacokinetic parameter of ASP2408: AUCtau
Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141
Area Under the Concentration-Time curve for a dosing interval (AUCtau)
Pharmacokinetic parameter of ASP2408: Cmax
Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141
Maximum Concentration (Cmax)
Pharmacokinetic parameter of ASP2408: Tmax
Time Frame: Days 1, 2 ,3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141
Time to Attain Cmax (Tmax)
Pharmacokinetic parameter of ASP2408: Ctrough
Time Frame: Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141
Trough Concentration (Ctrough)
Safety assessed by adverse events (AEs), laboratory tests, electrocardiograms (ECGs), physical examinations, pulse oximetry, vital signs and Anti-ASP2408 antibody (ADA) formulation
Time Frame: Up to 1 year
Secondary Outcomes
- Composite of pharmacokinetics of ASP2408: t1/2, Vz/F, CL/F,(Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141)
- Pharmacodynamic parameter of ASP2408: CD86 receptor occupancy(Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22,36, 38, 43, 50, 57, 66, 71, 72, 78, 85,113, 141)