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

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01565681

Collaborator

Kyowa Kirin Co., Ltd. (Industry)

109

Enrollment

Location

Arms

Duration (Months)

9.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics of ASKP1240 Healthy Volunteers	Drug: ASP1240 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

109 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Official Title:

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

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: ASKP1240 lowest dose	Drug: ASP1240 infusion
Experimental: Arm B: ASKP1240 second lowest dose	Drug: ASP1240 infusion
Experimental: Arm C: ASKP1240 third lowest dose	Drug: ASP1240 infusion
Experimental: Arm D: ASKP1240 fourth lowest dose	Drug: ASP1240 infusion
Experimental: Arm E: ASKP1240 fifth lowest dose	Drug: ASP1240 infusion
Experimental: Arm F: ASKP1240 middle dose	Drug: ASP1240 infusion
Experimental: Arm G: ASKP1240 sixth highest dose	Drug: ASP1240 infusion
Experimental: Arm H: ASKP1240 fifth highest dose	Drug: ASP1240 infusion
Experimental: Arm I: ASKP1240 fourth highest dose	Drug: ASP1240 infusion
Experimental: Arm J: ASKP1240 third highest dose	Drug: ASP1240 infusion
Experimental: Arm K: ASKP1240 second highest dose	Drug: ASP1240 infusion
Experimental: Arm L: ASKP1240 highest dose	Drug: ASP1240 infusion
Placebo Comparator: Arm M: Placebo Sodium Chloride solution	Drug: Placebo infusion Other Names: Sodium Chloride solution

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.
Kyowa Kirin Co., Ltd.

Investigators

Study Director: Medical Director, Astellas Pharma Global Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Astellas Pharma Global Development, Inc.

ClinicalTrials.gov Identifier:

NCT01565681

Other Study ID Numbers:

7163-CL-0101

First Posted:

Mar 29, 2012

Last Update Posted:

Dec 10, 2012

Last Verified:

Dec 1, 2012

Keywords provided by Astellas Pharma Global Development, Inc.

Healthy Volunteers

B cell CD40 receptor occupancy

anti-CD40 monoclonal antibody

Study Results

No Results Posted as of Dec 10, 2012