A Dose Escalation Study to Assess Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP2409 Following a Single Intravenous Dose in Patients With Rheumatoid Arthritis on Methotrexate
調査の概要
詳細な説明
This is a dose-escalation study. Sequential cohorts of subjects will receive increasing doses of ASP2409 or matching placebo.
Subjects in all cohorts will stay confined in the unit for 3 days. All subjects will have scheduled outpatient visits and be followed for a minimum of 90 days.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Alabama
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Anniston、Alabama、アメリカ、36027
- Pinnacle Research Group, LLC
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California
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Costa Mesa、California、アメリカ、92626
- West Coast Clinical Trials, Llc
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Florida
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Clearwater、Florida、アメリカ、33765
- Clinical Research of West Florida, Inc.
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Edgewater、Florida、アメリカ、32132
- Riverside Clinical Research
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North Carolina
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Raleigh、North Carolina、アメリカ、27612
- Carolina Phase 1 Research
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Ohio
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Cincinnati、Ohio、アメリカ、45255
- Community Research
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ、73122
- Lynn Health Science Institute
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Pennsylvania
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Duncansville、Pennsylvania、アメリカ、16635
- Altoona Center for Clinical Research
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Texas
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Dallas、Texas、アメリカ、75231
- Metroplex Clinical Research Center, LLC
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San Antonio、Texas、アメリカ、78217
- Texas Arthritis Research Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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 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.
- Female subject must not donate ova starting at Screening and throughout the Treatment and Observation period and for ≥ 120 days after final study drug administration.
- Male subject must not donate sperm starting at Screening and throughout the Treatment and Observation period and for at least ≥ 120 days after final study drug administration.
- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the Treatment and Observation period and for ≥ 120 days after final study drug administration.
- 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 study drug infusion, AND
- at a stable dose (10 - 25 mg/week) for ≥ 28 days prior to study drug infusion and throughout the study.
Subjects on the following medications must remain on a stable regimen: non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, hydroxychloroquine (Plaquenil®), sulfasalazine, oral corticosteroids (≤ 10 mg of prednisone, or equivalent, daily) or low dose opioids (≤ 30 mg of oral morphine, or equivalent, daily) for
≥ 28 days prior to Screening and remain so throughout the Treatment and Observation Period. (The start of Plaquenil and sulfasalazine must be ≥ 2 months prior to study drug infusion.)
- Subject is highly likely to comply with the protocol and complete the study.
Exclusion Criteria:
- 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.
- Subject has previously received any antibody or therapeutic biologic product within 56 days or 5 half-lives, whichever is longer, prior to study drug infusion.
- 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 study drug infusion.
- Subject is participating in another clinical trial or has participated in another dose group of the current trial.
- Subject has had any significant blood loss, donated one 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 clinic admission on Day -1.
- Subject has taken Orencia® (abatacept), Nulojix® (belatacept) or any other CTLA4-Ig molecule.
- Subject has any other condition which precludes the subject's participation in the trial.
- Subject has a history of prolonged QT syndrome.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:ASP2409 Dose Escalation
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intravenous (IV)
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プラセボコンパレーター:Placebo Dose Escalation
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intravenous (IV)
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
---|---|
Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 up to the last quantifiable concentration (AUClast)
時間枠:Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Pharmacokinetics of ASP2409 concentration: Area under the concentration - time curve from time 0 extrapolated to infinity (AUCinf)
時間枠:Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Pharmacokinetics of ASP2409 concentration: Maximum concentration (Cmax)
時間枠:Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Safety assessed by adverse events
時間枠:Up to 1 year
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Up to 1 year
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Safety assessed by laboratory tests
時間枠:Up to 1 year
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Up to 1 year
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Safety assessed by electrocardiograms (ECGs)
時間枠:Up to 1 year
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Up to 1 year
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Safety assessed by physical examinations
時間枠:Up to 1 year
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Up to 1 year
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Safety assessed by vital signs
時間枠:Up to 1 year
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Up to 1 year
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Safety assessed by anti-ASP2409 antibody formation
時間枠:Up to 1 year
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Up to 1 year
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Composite of pharmacokinetics of ASP2409 concentration: tmax, t1/2, Vz, Vss, CLtot
時間枠:Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Time to attain Cmax (tmax), apparent terminal elimination half-life (t1/2), terminal phase volume (Vz), volume of distribution at steady-state (Vss), and total body clearance (CLtot)
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Days 1-8, Days 15, 22, 29, 43, 60, 90, and 120
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Pharmacodynamics of ASP2409: CD86 receptor occupancy
時間枠:Days 1-3, Days 5, 8, 15, 22, 29, 43, 60, and 90
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Cluster of Differentiation 86 (CD86), a co-stimulatory ligand on lymphocytes
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Days 1-3, Days 5, 8, 15, 22, 29, 43, 60, and 90
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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