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

Study Overview
=================
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.

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

Conditions
-----------------
Pharmacokinetics of ASKP1240, Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: ASP1240
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: ASKP1240 lowest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm B: ASKP1240 second lowest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm C: ASKP1240 third lowest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm D: ASKP1240 fourth lowest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm E: ASKP1240 fifth lowest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm F: ASKP1240 middle dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm G: ASKP1240 sixth highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm H: ASKP1240 fifth highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm I: ASKP1240 fourth highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm J: ASKP1240 third highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm K: ASKP1240 second highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Experimental: Arm L: ASKP1240 highest dose<br> | Drug: ASP1240<br>* infusion<br>|
| Placebo Comparator: Arm M: Placebo<br>Sodium Chloride solution | Drug: Placebo<br>* infusion<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy Volunteers, B cell CD40 receptor occupancy, anti-CD40 monoclonal antibody