Study of ASKP1240 After a Single Intravenous Dose at Escalating Dose Levels in Healthy Subjects

Healthy Volunteers Clinical Trial

Official title:

A Phase 1 Single Ascending Dose Study of ASKP1240 in Healthy Male and Female Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565681
• Other study ID #: 7163-CL-0101
• Status: Completed
• Phase: Phase 1
• First received: March 27, 2012
• Last updated: December 7, 2012
• Start date: January 2009
• Est. completion date: December 2009

Study information

• Verified date: December 2012
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• The subject has a history of severe allergic or anaphylactic reactions

• 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)

• 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

• 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)

• The subject is known positive for human immunodeficiency virus (HIV) antibody

• The subject has a positive test for hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg)

• The subject has at screening or clinic check in that:

1. white blood cell count (WBC) is < 3.5 or > upper limit of normal

2. absolute neutrophil count (ANC) is <1.5 or > upper limit of normal

3. platelet count (PLT) is outside the normal limit

4. serum creatinine, total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) are > upper limit of normal

5. creatine phosphokinase (CPK) is > two times upper limit of normal

6. international normalized ratio (INR) is > upper limit of normal

7. 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

• The subject has received a vaccine within 60 days prior to study drug administration

• The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration.

• The subject has received any antibody or biologic product within 6 months prior to study drug administration

• The subject has received any systemic steroid within 2 months prior to study drug administration

• 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

• The subject has received an experimental agent within 30 days or ten half-lives, whichever is longer, prior to study drug administration

• The subject is participating in another clinical trial or has participated in another dose group of the current trial

• 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

• 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

• The subject has a history of thromboembolic or vascular disease especially deep vein thrombosis, pulmonary embolism and varices

• The subject has a positive test for tuberculosis

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Volunteers
• Pharmacokinetics of ASKP1240

Intervention

Drug:
• ASP1240
infusion
• Placebo
infusion

Locations

Country	Name	City	State
United States	Parexel	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Kyowa Hakko Kirin Company, Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamic variable: Individual subject cell surface antigen (CD40) occupancy levels over time	binding of ASKP1240-biotin to B cells	Days 1-3, 5, 8,15, 22, 29, 43, 60, 75, and 90	No
Primary	Pharmacokinetics profile: AUCinf and Cmax	Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) and Maximum concentration of study drug (Cmax)	Days 1-8,15, 22, 29, 43 and 60	No
Secondary	Pharmacokinetics profile: AUClast, tmax, t1/2, Vz, and CLtot	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)	Days 1-8,15, 22, 29, 43 and 60	No
Secondary	Total lymphocyte count	product of the white blood count (WBC) and percent lymphocytes [from differential]	Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60	No
Secondary	Peripheral lymphocyte subset quantification	leukocycte phenotypes: CD3, CD4, CD8,CD16, and CD20	Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60	No
Secondary	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	Yes