A Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate

NCT02171143 | Completed Phase 1

• 1 other identifier: 2409-CL-0104
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 10

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.

Conditions

Rheumatoid Arthritis; Pharmacokinetics of ASP2409

Keywords

ASP2409; Rheumatoid Arthritis; methotrexate

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast)

  Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120

• Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf)

  Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120

• Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)

  Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120

• Safety assessed by adverse events

  Up to 1 year

• Safety assessed by laboratory tests

  Up to 1 year

• Safety assessed by electrocardiograms (ECGs)

  Up to 1 year

• Safety assessed by physical examinations

  Up to 1 year

• Safety assessed by vital signs

  Up to 1 year

• Safety assessed by anti-ASP2409 antibody formation

  Up to 1 year

Secondary Outcomes (2)

• 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

Study Arms (2)

ASP2409 Dose Escalation

EXPERIMENTAL

Drug: ASP2409

Placebo Dose Escalation

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ASP2409 DRUG

intravenous (IV)

ASP2409 Dose Escalation

Placebo DRUG

intravenous (IV)

Placebo Dose Escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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 -1.
• 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.
• Acceptable forms include:
• Established use or oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/ cream/suppository.
• Female subject must not be breastfeeding at Screening or during the Treatment and Observation period and for ≥ 120 days after final study drug administration.

You may not qualify if:

• 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 -1.
• Subject has/had a viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to Day -1.
• 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.
• Subject's laboratory test results at Screening:
• alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are ˃ 2 times the upper limit of normal, AND/OR
• are outside the normal limits and considered by the Investigator to be clinically significant with regard to the remaining per-protocol laboratory tests.
• Subject received any live or live attenuated vaccine within 30 days prior to study drug infusion.
• Subject received any systemic immunosuppressant agent, other than (MTX) or stable steroid regimen, within 2 months prior to study drug infusion.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (10)

Pinnacle Research Group, LLC

Anniston, Alabama, 36027, United States

Location

West Coast Clinical Trials, LLC

Costa Mesa, California, 92626, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

Carolina Phase 1 Research

Raleigh, North Carolina, 27612, United States

Location

Community Research

Cincinnati, Ohio, 45255, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73122, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Metroplex Clinical Research Center, LLC

Dallas, Texas, 75231, United States

Location

Texas Arthritis Research Center

San Antonio, Texas, 78217, United States

Location

Related Publications (1)

• Zhang W, Kernstock RM, Karrer EE, Cohen SB, Chindalore VL, Kivitz AJ, Blahunka PC, Delgado-Herrera L, Zeiher BG, Samberg NL, Garg JP. A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy. Clin Pharmacol Drug Dev. 2016 Jul;5(4):259-68. doi: 10.1002/cpdd.237. Epub 2016 Jan 8.

  PMID: 27310327 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ASP2409

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Senior Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 24, 2014
• Study Start: April 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 24, 2014

Record last verified: 2014-06

Locations

US (10)