Study of ASKP1240 After a Single Intravenous Dose at Escalating Dose Levels in Healthy Subjects
- Conditions
- Pharmacokinetics of ASKP1240Healthy Volunteers
- Interventions
- Drug: ASP1240Drug: Placebo
- Registration Number
- NCT01565681
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
The objective of this study is to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of ASKP1240 after a single intravenous dose at escalating dose levels in healthy subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 109
- The subject weighs at least 50 kg, and has a body mass index (BMI) of 18 to 32 kg/m2 inclusive
- The female subject must be of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year with follicle stimulating hormone [FSH] > 40 U/L)
- Male subject agrees to no sperm donation until end of study or 90 days post dose, whichever is longer
- The subject is highly likely to comply with the protocol and complete the study
- The subject has a negative urine screen for drugs of abuse, and negative blood or breathalyzer alcohol screen at Screening and clinic admission on Day 1
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The subject has a history of severe allergic or anaphylactic reactions
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The subject has 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 2 years prior to screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits)
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The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check in
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The subject has a supine mean systolic blood pressure < 90 or > 160 mmHg and a mean diastolic blood pressure < 50 or > 90 mmHg, or pulse rate higher than 100 beats per min (bpm), either at screening or clinic check in (blood pressure measurements taken in triplicate after subject has been resting in a supine position for a minimum of 5 minutes)
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The subject is known positive for human immunodeficiency virus (HIV) antibody
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The subject has a positive test for hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg)
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The subject has at screening or clinic check in that:
- white blood cell count (WBC) is < 3.5 or > upper limit of normal
- absolute neutrophil count (ANC) is <1.5 or > upper limit of normal
- platelet count (PLT) is outside the normal limit
- serum creatinine, total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) are > upper limit of normal
- creatine phosphokinase (CPK) is > two times upper limit of normal
- international normalized ratio (INR) is > upper limit of normal
- OR remaining laboratory tests are outside the normal limits and considered by the investigator to be clinically significant with regard to the remaining per protocol laboratory tests
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The subject has received a vaccine within 60 days prior to study drug administration
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The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration.
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The subject has received any antibody or biologic product within 6 months prior to study drug administration
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The subject has received any systemic steroid within 2 months prior to study drug administration
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The subject has had treatment with prescription or non-prescription drugs, including complementary and alternative medicines (CAM) and excluding over-the-counter (OTC) allergy medications, nasal steroids, nasal inhalers, oral contraceptives, stable hormone replacement therapy (HRT; per Investigator judgment and dose change not expected during study), and intermittent acetaminophen, within 14 days prior to study drug administration
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The subject has received an experimental agent within 30 days or ten half-lives, whichever is longer, prior to study drug administration
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The subject is participating in another clinical trial or has participated in another dose group of the current trial
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The subject has donated or has had significant blood loss or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to dosing
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The subject has a history of heavy smoking or has used tobacco-containing products and nicotine or nicotine-containing products in the past six months prior to Screening
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The subject has a history of thromboembolic or vascular disease especially deep vein thrombosis, pulmonary embolism and varices
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The subject has a positive test for tuberculosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: ASKP1240 lowest dose ASP1240 - Arm B: ASKP1240 second lowest dose ASP1240 - Arm C: ASKP1240 third lowest dose ASP1240 - Arm D: ASKP1240 fourth lowest dose ASP1240 - Arm E: ASKP1240 fifth lowest dose ASP1240 - Arm F: ASKP1240 middle dose ASP1240 - Arm G: ASKP1240 sixth highest dose ASP1240 - Arm H: ASKP1240 fifth highest dose ASP1240 - Arm I: ASKP1240 fourth highest dose ASP1240 - Arm J: ASKP1240 third highest dose ASP1240 - Arm L: ASKP1240 highest dose ASP1240 - Arm M: Placebo Placebo Sodium Chloride solution Arm K: ASKP1240 second highest dose ASP1240 -
- Primary Outcome Measures
Name Time Method Pharmacodynamic variable: Individual subject cell surface antigen (CD40) occupancy levels over time Days 1-3, 5, 8,15, 22, 29, 43, 60, 75, and 90 binding of ASKP1240-biotin to B cells
Pharmacokinetics profile: AUCinf and Cmax Days 1-8,15, 22, 29, 43 and 60 Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) and Maximum concentration of study drug (Cmax)
- Secondary Outcome Measures
Name Time Method Pharmacokinetics profile: AUClast, tmax, t1/2, Vz, and CLtot Days 1-8,15, 22, 29, 43 and 60 Area under the plasma concentration-time curve from time 0 up to the last quantifiable concentration (AUClast),Time to attain Cmax (tmax), Apparent terminal elimination of half-life (t1/2), Apparent volume of distribution ( Vz), and Total body clearance (CLtot)
Total lymphocyte count Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60 product of the white blood count (WBC) and percent lymphocytes \[from differential\]
Peripheral lymphocyte subset quantification Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60 leukocycte phenotypes: CD3, CD4, CD8,CD16, and CD20
Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs), physical examination, pulse oximetry, and incidence of anti-ASKP1240 antibody formation Up to day 90
Trial Locations
- Locations (1)
Parexel
🇺🇸Baltimore, Maryland, United States