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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02698657
Recruitment Status : Completed
First Posted : March 4, 2016
Last Update Posted : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

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).

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis (RA) Drug: ASP5094 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Randomized, Placebo-controlled, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP5094 Following Multiple Intravenous Doses in Subjects With Rheumatoid Arthritis on Methotrexate
Actual Study Start Date : February 23, 2016
Actual Primary Completion Date : September 7, 2017
Actual Study Completion Date : September 7, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: ASP5094
Intravenous (IV)

Placebo Comparator: 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.
Drug: Placebo
Intravenous (IV)




Primary Outcome Measures :
  1. Number of Participants with Treatment-Emergent Adverse Events [ Time Frame: From first dose of study drug up to end of study (up to 141 days) ]
    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.

  2. Change from Baseline in Total Lymphocyte Counts [ Time Frame: Baseline and days 29, 57, 85, 113, 141 ]
  3. Change from Baseline in Peripheral Lymphocyte Subsets: CD19 [ Time Frame: Baseline and days 29 (predose), 57 (predose), 85, 113, 141 ]
  4. Change from Baseline in Peripheral Lymphocyte Subsets: CD19/Lymphocytes [ Time Frame: Baseline and days 29 (predose), 57 (predose), 85, 113, 141 ]
  5. Change from Baseline in Peripheral Lymphocyte Subsets: CD3 [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  6. Change from Baseline in Peripheral Lymphocyte Subsets: CD3/Lymphocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  7. Change from Baseline in Peripheral Lymphocyte Subsets: CD4 [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  8. Change from Baseline in Peripheral Lymphocyte Subsets: CD4/Lymphocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  9. Change from Baseline in Peripheral Lymphocyte Subsets: CD8 [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  10. Change from Baseline in Peripheral Lymphocyte Subsets: CD8/Lymphocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  11. Change from Baseline in Peripheral Lymphocyte Subsets: Granulocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  12. Change from Baseline in Peripheral Lymphocyte Subsets: Granulocytes/Leukocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  13. Change from Baseline in Peripheral Lymphocyte Subsets: Natural Killer Cell Subset/Lymphocytes [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  14. Change from Baseline in Peripheral Lymphocyte Subsets: Natural Killer Cells [ Time Frame: Baseline and Days 29 (predose), 57 (predose), 85, 113, 141 ]
  15. Number of Participants with Anti-ASP5094 Antibody Formation [ Time Frame: Days 1 (predose), 29 (predose), 57 (predose), 71, 85, 113 and 141 ]
  16. 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) [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  17. Maximum Concentration (Cmax) of ASP5094 [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  18. Time to maximum concentration (tmax) of ASP5094 [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  19. Concentration immediately prior to dosing at multiple dosing (Ctrough) for ASP5094 [ Time Frame: Predose on days 29, 57, and 85 ]
  20. Accumulation ratio calculated using the maximum concentration (R3ac[Cmax]) for ASP5094 [ Time Frame: Day 57 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  21. Accumulation ratio calculated using the area under the concentration-time curve (R3ac[AUC]) for ASP5094 [ Time Frame: Day 57 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]

Secondary Outcome Measures :
  1. Terminal elimination half-life (t1/2) [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  2. Total clearance after intravenous dosing (CL) [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  3. Volume of distribution after intravenous dosing during the terminal elimination phase (VzF) [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]
  4. Percentage of Fluctuation [ Time Frame: Day 1 predose, 0.5, 24, 96, 168, 216, 336, 504, 672 hours postdose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02698657


Locations
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United States, Alabama
Site US10002
Anniston, Alabama, United States, 36207
United States, Florida
Site US10008
DeBary, Florida, United States, 32713-1818
Site US10004
Jacksonville, Florida, United States, 32216
Site US10009
Miami Lakes, Florida, United States, 33014
United States, Pennsylvania
Site US10003
Duncansville, Pennsylvania, United States, 16635
United States, Tennessee
Site US10010
Memphis, Tennessee, United States, 38119
United States, Texas
Site US10001
Dallas, Texas, United States, 75231
Poland
Site PL48009
Elblag, Poland, 82-300
Site PL48011
Krakow, Poland, 31-637
Site PL48006
Lodz, Poland, 91-347
Site PL48007
Stalowa Wola, Poland
Site PL48003
Warszawa, Poland, 00-660
Site PL48008
Wroclaw, Poland, 50-556
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
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Study Director: Senior Medical Director Astellas Pharma Global Development, Inc.
Additional Information:
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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02698657    
Other Study ID Numbers: 5094-CL-0102
2015-004562-28 ( EudraCT Number )
First Posted: March 4, 2016    Key Record Dates
Last Update Posted: June 28, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Rheumatoid arthritis (RA)
Methotrexate
ASP5094
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases