Clinical trial NCT02125435: A Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP2408 Following Single Intravenous Doses in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of ASP2408 Following Single Intravenous Doses in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Pharmacokinetics of ASP2408
Keywords: Healthy subjects
ASP2408
pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-04-29
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of single ascending intravenous (IV) doses of ASP2408 in non-elderly, healthy male and female subjects and to evaluate the pharmacodynamics of ASP2408.

Detailed description: This is single-dose escalation study composed of 8 sequential cohorts of healthy subjects receiving increasing doses of intravenously administered ASP2408 or matching placebo. Subjects will be confined in the clinic for 8 days.

Eligibility criteria: Inclusion Criteria:

* Subject weighs at least 50 kg, and has a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive.
* Results of subject's 12-lead electrocardiogram (ECG) are normal or, if abnormal, the abnormality is not clinically significant as determined by the investigator.
* Female subject must be at least two years postmenopausal OR surgically sterile (with documentation provided by a healthcare professional) and not pregnant or lactating.
* Male subject agrees to the use of male condoms until the end of study or 60 days post dose, whichever is longer.
* Subject is highly likely to comply with the protocol and complete the study.

Exclusion Criteria:

* Subject has a history of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding adequately treated non-melanoma skin cancer.
* Subject has a history of severe allergic or anaphylactic reactions.
* Subject is a female of child-bearing potential.
* 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 2 years (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.
* Subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check-in.
* Subject has a past history of opportunistic infection.
* Subject has a supine mean systolic blood pressure \< 90 or \> 160 mmHg and a mean diastolic blood pressure \< 50 or \> 90 mmHg, or mean pulse rate higher than 100 beats per min (bpm).
* Subject is known positive for human immunodeficiency virus (HIV) antibody.
* Subject has a positive TB skin test or Quantiferon Gold test or T-SPOT® 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.
* Subject's laboratory test results:

  * alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), are greater than 1.5 times the upper limit of normal
  * 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 vaccine within 60 days prior to study drug administration.
* Subject received any systemic immunosuppressant agent within 2 months prior to study drug administration.
* Subject has previously received any antibody or therapeutic biologic product prior to study drug administration.
* Subject received any systemic steroid within 2 months or steroid inhaler within 1 month prior to study drug administration.
* Subject has had treatment with prescription, non-prescription or complementary and alternative medicines (CAM) within 14 days prior to study drug administration.
* Subject has received an experimental agent within 30 days or five half-lives, whichever is longer, prior to study drug administration.
* 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 a history of heavy smoking or has used tobacco-containing products and nicotine or nicotine-containing products in the past six months.

Primary outcomes:
measure: Pharmacokinetic parameter of ASP2408:AUClast
timeFrame: Days 1-8, 15, 22, 29, 43, 60, 90
measure: Pharmacokinetic parameter of ASP2408: AUCinf
timeFrame: Days 1 -8, 15, 22, 29, 43, 60, 90
measure: Pharmacokinetic parameter of ASP2408:Cmax
timeFrame: Days 1-8, 15, 22, 29, 43, 60, 90
measure: Safety assessed by adverse events, laboratory tests, immunoglobulin, 12-lead electrocardiograms (ECGs), vital signs and anti-2408 antibody formulation
timeFrame: up to 90 days
Secondary outcomes:
measure: Composite of pharmacokinetics of ASP2408: tmax, t1/2, Vz, CLtot
timeFrame: Days 1-8, 15, 22, 29, 43, 60, 90
measure: Pharmacodynamic parameters of ASP2408: CD80 and CD86 receptor occupancy
timeFrame: Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90
measure: Total lymphocyte count
timeFrame: Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90
measure: Peripheral lymphocyte subset quantification
timeFrame: Days 1-3, 5, 8, 15, 22, 29, 43, 60, 90
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: PAREXEL International
state: Maryland
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: