A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP5094 Following Multiple Intravenous Doses in Subjects With Rheumatoid Arthritis on Methotrexate

NCT ID: NCT02698657

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-23
• Study Completion Date: 2017-09-07

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of multiple ascending intravenous doses of ASP5094 in male and female subjects with rheumatoid arthritis (RA) on methotrexate (MTX).

Conditions

Rheumatoid Arthritis (RA)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

ASP5094 Dose Escalation

Three sequential cohorts will receive increasing intravenous doses of ASP5094. After all subjects in a cohort have completed study procedures the overall safety and tolerability of the dose will be determined after evaluation of the safety data. If there are no events which meet the stopping criteria, the next sequential cohort will begin enrollment while the current subjects continue through the third dose and the remainder of the study.

Group Type: EXPERIMENTAL

ASP5094

Intervention Type: DRUG

Intravenous (IV)

Placebo Dose Escalation

Three sequential cohorts will receive increasing intravenous doses of Placebo. After all subjects in a cohort have completed study procedures the overall safety and tolerability of the dose will be determined after evaluation of the safety data. If there are no events which meet the stopping criteria, the next sequential cohort will begin enrollment while the current subjects continue through the third dose and the remainder of the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous (IV)

Interventions

ASP5094

Intravenous (IV)

Intervention Type: DRUG

Placebo

Intravenous (IV)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject has a body mass index (BMI) of ≤ 35 kg/m2, inclusive, and must weigh at least 50 kg at screening.
• Subject has absolute neutrophil count within normal limits at screening. The assessment may be repeated once during screening.
• Subject has 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 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 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:

• Nonsteroidal antiinflammatory drugs (NSAIDs), selective cyclooxygenase-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,
• Hydroxychloroquine (Plaquenil®) and sulfasalazine (e.g., Azulfidine®) must have started ≥ 2 months, and be stable for ≥ 28 days, prior to day 1.
• Female subject must be either:

• Of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile
• Or, if of childbearing potential, Agree not to try to become pregnant during the study and for 60 days after the final study drug administration; must have a negative urine pregnancy test at screening and day 1, And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control† (at least 1 of which must be a barrier method) starting at screening and throughout the study period and for 60 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days.
• Female subject must not donate ova starting at screening and throughout the study period, and for 60 days after the final study drug administration.
• Male subject and his female spouse/partner who is of childbearing potential must be using highly effective forms of contraception consisting of 2 forms of birth control† (1 of which must be a barrier method) starting at screening and continue throughout the study period and for 60 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period, and for 60 days after the final study drug administration
• Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until completion of the last study visit.

Exclusion Criteria

• Subject has an ongoing clinically significant systemic disease such as uncompensated heart failure, uncontrolled diabetes mellitus, severe hepatic failure, severe pulmonary disease or inflammatory bowel disease.
• Subject has a history of any malignancy in the past 5 years, except for adequately-treated, nonmelanoma skin cancer and adequately-treated in-situ cervical cancer.
• Subject has a history of severe allergic or anaphylactic reactions to drugs.
• 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: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits).
• Subject has an ongoing infection or has had an infection requiring intravenous antibiotics within 1 month prior to day 1.
• Subject has a known history of a positive test for human immunodeficiency virus (HIV) antibody.
• Subject has a past history of serious opportunistic infection.
• Subject has a positive QuantiFERON-TB Gold test within 90 days of, or at screening, and has not completed an adequate course of antimicrobial therapy per Centers for Disease Control or local guidelines.
• Subject's laboratory test results at screening or prior to study drug dosing on day 1:

• Outside the normal limits and considered by the investigator to be clinically significant with regard to the remaining per-protocol laboratory tests, and/or
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) are > 2 times the upper limit of normal.
• Subject received any live or live-attenuated vaccine within 30 days prior to day 1.
• Subject received any of the following:

• Oral or injectable gold, azathioprine, penicillamine, cyclosporine, tacrolimus or tofacitinib (Xeljanz®) within 30 days prior to day 1.
• Anakinra (Kineret®), etanercept (Enbrel®), adalimumab (Humira®), tocilizumab (Actemra®), infliximab (Remicade®), or golimumab (Simponi®) within 60 days prior to day 1.
• Leflunomide (Arava®) within 60 days prior to day 1, unless the subject has undergone cholestyramine washout at least 30 days prior to day 1.
• Certolizumab (Cimzia®) and abatacept (Orencia®) within 90 days prior to day 1.
• Rituximab (Rituxan®) or any other antiCD20 antibody, and cyclophosphamide within 180 days prior to day 1.
• Treatment with any other conventional disease modifying antirheumatic drugs (DMARDs), or treatment with any other biologics not previously noted within 28 days or 5 half-lives, whichever is longer, prior to day 1.
• Subject has participated in a previous clinical study with treatment with ASP5094 or has participated in another dose cohort of the current trial.
• Subject has previously received an experimental agent within 28 days or 5 half-lives, whichever is longer, prior to day 1.
• Subject has had any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to day 1.
• Subject had surgery or has a planned elective surgery (including oral surgery) within 1 month prior to screening and 3 months after last study drug administration.
• Subject has a wound that is currently healing.
• Subject has any other condition, which in the opinion of the investigator, precludes the subject's participation in the trial.
• Subject is an employee of the Astellas group or vendors involved in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senior Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Site US10002

Anniston, Alabama, United States

Site US10008

DeBary, Florida, United States

Site US10004

Jacksonville, Florida, United States

Site US10009

Miami Lakes, Florida, United States

Site US10003

Duncansville, Pennsylvania, United States

Site US10010

Memphis, Tennessee, United States

Site US10001

Dallas, Texas, United States

Site PL48009

Elblag, , Poland

Site PL48011

Krakow, , Poland

Site PL48006

Lodz, , Poland

Site PL48007

Stalowa Wola, , Poland

Site PL48003

Warsaw, , Poland

Site PL48008

Wroclaw, , Poland

Countries

United States; Poland

Related Links

https://astellasclinicalstudyresults.com/study.aspx?ID=326

Link to results on the Astellas Clinical Study Results website

Other Identifiers

2015-004562-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5094-CL-0102

Identifier Type: -

Identifier Source: org_study_id