A Study To Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of ASP2408 After Multiple Dose Subcutaneous Injections in Patients With Rheumatoid Arthritis on Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02052375
• Other study ID #: 2408-CL-0201
• Status: Completed
• Phase: Phase 1
• First received: January 30, 2014
• Last updated: February 5, 2014
• Start date: June 2012
• Est. completion date: December 2013

Study information

• Verified date: February 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Subject weighs at least 50 kg.

• Subject has a body mass index (BMI) of = 35 kg/m2.

• 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.

• Hydroxychloroquine (Plaquenil®) and sulfasalazine must have started = 2 months, and be stable for = 28 days, prior to Day 1.

Exclusion Criteria:

• Subject has an ongoing infection or has had an infection requiring intravenous antibiotics within 1 month prior to Day 1.

• 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 1.

• Subject received any of the following:

• Anakinra (Kineret®), etanercept (Enbrel®), or adalimumab (Humira®) within 60 days prior to Day 1.

• Rituximab (Rituxan®) or any other anti-CD20 antibody within 180 days prior to Day 1.

• 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 1.

• Oral or injectable gold, azathioprine, penicillamine, cyclosporine, or tacrolimus within 30 days prior to Day 1.

• Cyclophosphamide within 180 days prior to Day 1.

• Subject has received any CTLA4-Ig molecule (including, but not limited to abatacept [Orencia®] and belatacept [Nulojix]).

• Subject has participated in a previous clinical study with treatment with ASP2408 or ASP2409 or has participated in another dose cohort of the current trial.

• Subject has previously participated in any interventional clinical study, or has received an experimental agent within 56 days or 5 half-lives, whichever is longer, prior to Day 1.

• Subject has a history of prolonged QT syndrome.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Pharmacokinetics of ASP2408
• Rheumatoid Arthritis

Intervention

Drug:
• ASP2408
subcutaneous injection
• Placebo
subcutaneous injection

Locations

Country	Name	City	State
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Metroplex Clinical Research Center, LLC	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameter of ASP2408: AUCtau	Area Under the Concentration-Time curve for a dosing interval (AUCtau)	Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141	No
Primary	Pharmacokinetic parameter of ASP2408: Cmax	Maximum Concentration (Cmax)	Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141	No
Primary	Pharmacokinetic parameter of ASP2408: Tmax	Time to Attain Cmax (Tmax)	Days 1, 2 ,3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141	No
Primary	Pharmacokinetic parameter of ASP2408: Ctrough	Trough Concentration (Ctrough)	Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141	No
Primary	Safety assessed by adverse events (AEs), laboratory tests, electrocardiograms (ECGs), physical examinations, pulse oximetry, vital signs and Anti-ASP2408 antibody (ADA) formulation		Up to 1 year	No
Secondary	Composite of pharmacokinetics of ASP2408: t1/2, Vz/F, CL/F,	Apparent Terminal Elimination Half-life (t1/2), Volume of distribution (Vz/F), Apparent Body Clearance (CL/F)	Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22, 36, 38, 43, 50, 57, 66, 71, 78, 85, 113, 141	No
Secondary	Pharmacodynamic parameter of ASP2408: CD86 receptor occupancy	Cluster of Differentiation 86, a co-stimulatory ligand on antigen-presenting cells; alternate notation for B7.2 (CD86)	Days 1, 2, 3, 4, 5, 6, 8, 10, 15, 22,36, 38, 43, 50, 57, 66, 71, 72, 78, 85,113, 141	No