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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Pharmacokinetics of ASKP1240
• Intervention / Treatment: Drug: Placebo; Drug: ASP1240

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 29, 2012

Study Record Updates

• Last Update Posted (Estimate): December 10, 2012
• Last Update Submitted That Met QC Criteria: December 7, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Healthy Volunteers; B cell CD40 receptor occupancy; anti-CD40 monoclonal antibody
• Other Study ID Numbers: 7163-CL-0101