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

NCT02698657 | Completed Phase 1 DMC

• 2 other identifiers: 5094-CL-01022015-004562-28
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 13

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)

Keywords

Rheumatoid arthritis (RA); Methotrexate; ASP5094

Outcome Measures

Primary Outcomes (21)

• Number of Participants with Treatment-Emergent Adverse Events

  A treatment-emergent adverse event (TEAE) is defined as a newly occurring or worsening adverse event (AE) observed after starting administration of study drug up until the end of study visit, inclusive. This includes abnormal laboratory tests, vital signs or electrocardiogram data that are defined as AEs if the abnormality induces clinical signs or symptoms, requires active intervention, interruption or discontinuation of study drug or is clinically significant in the investigator's opinion. A serious AE (SAE) is defined as an AE with an outcome that results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly, or birth defect or requires inpatient hospitalization or leads to prolongation of hospitalization.

  From first dose of study drug up to end of study (up to 141 days)

• Change from Baseline in Total Lymphocyte Counts

  Baseline and days 29, 57, 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD19

  Baseline and days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD19/Lymphocytes

  Baseline and days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD3

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD3/Lymphocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD4

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD4/Lymphocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD8

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: CD8/Lymphocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: Granulocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: Granulocytes/Leukocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: Natural Killer Cell Subset/Lymphocytes

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Change from Baseline in Peripheral Lymphocyte Subsets: Natural Killer Cells

  Baseline and Days 29 (predose), 57 (predose), 85, 113, 141

• Number of Participants with Anti-ASP5094 Antibody Formation

  Days 1 (predose), 29 (predose), 57 (predose), 71, 85, 113 and 141

• Area under the concentration-time curve from the time of dosing on day 1 to the end of the 4-week dosing interval for ASP5094 (AUC)

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Maximum Concentration (Cmax) of ASP5094

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Time to maximum concentration (tmax) of ASP5094

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Concentration immediately prior to dosing at multiple dosing (Ctrough) for ASP5094

  Predose on days 29, 57, and 85

• Accumulation ratio calculated using the maximum concentration (R3ac[Cmax]) for ASP5094

  Day 57 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Accumulation ratio calculated using the area under the concentration-time curve (R3ac[AUC]) for ASP5094

  Day 57 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

Secondary Outcomes (4)

• Terminal elimination half-life (t1/2)

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Total clearance after intravenous dosing (CL)

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Volume of distribution after intravenous dosing during the terminal elimination phase (VzF)

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

• Percentage of Fluctuation

  Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose

Study Arms (2)

ASP5094 Dose Escalation

EXPERIMENTAL

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.

Drug: ASP5094

Placebo Dose Escalation

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

ASP5094 DRUG

Intravenous (IV)

ASP5094 Dose Escalation

Placebo DRUG

Intravenous (IV)

Placebo Dose Escalation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (13)

Site US10002

Anniston, Alabama, 36207, United States

Location

Site US10008

DeBary, Florida, 32713-1818, United States

Location

Site US10004

Jacksonville, Florida, 32216, United States

Location

Site US10009

Miami Lakes, Florida, 33014, United States

Location

Site US10003

Duncansville, Pennsylvania, 16635, United States

Location

Site US10010

Memphis, Tennessee, 38119, United States

Location

Site US10001

Dallas, Texas, 75231, United States

Location

Site PL48009

Elblag, 82-300, Poland

Location

Site PL48011

Krakow, 31-637, Poland

Location

Site PL48006

Lodz, 91-347, Poland

Location

Site PL48007

Stalowa Wola, Poland

Location

Site PL48003

Warsaw, 00-660, Poland

Location

Site PL48008

Wroclaw, 50-556, Poland

Location

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Arthritis, Rheumatoid

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2016
• First Posted: March 4, 2016
• Study Start: February 23, 2016
• Primary Completion: September 7, 2017
• Study Completion: September 7, 2017
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); PL (6)