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

NCT01565681 | Completed Phase 1

• 1 other identifier: 7163-CL-0101
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics of ASKP1240; Healthy Volunteers

Keywords

Healthy Volunteers; B cell CD40 receptor occupancy; anti-CD40 monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Pharmacokinetics profile: AUClast, tmax, t1/2, Vz, and CLtot

  Days 1-8,15, 22, 29, 43 and 60

• Total lymphocyte count

  Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60

• Peripheral lymphocyte subset quantification

  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

Study Arms (13)

Arm A: ASKP1240 lowest dose

EXPERIMENTAL

Drug: ASP1240

Arm B: ASKP1240 second lowest dose

EXPERIMENTAL

Drug: ASP1240

Arm C: ASKP1240 third lowest dose

EXPERIMENTAL

Drug: ASP1240

Arm D: ASKP1240 fourth lowest dose

EXPERIMENTAL

Drug: ASP1240

Arm E: ASKP1240 fifth lowest dose

EXPERIMENTAL

Drug: ASP1240

Arm F: ASKP1240 middle dose

EXPERIMENTAL

Drug: ASP1240

Arm G: ASKP1240 sixth highest dose

EXPERIMENTAL

Drug: ASP1240

Arm H: ASKP1240 fifth highest dose

EXPERIMENTAL

Drug: ASP1240

Arm I: ASKP1240 fourth highest dose

EXPERIMENTAL

Drug: ASP1240

Arm J: ASKP1240 third highest dose

EXPERIMENTAL

Drug: ASP1240

Arm K: ASKP1240 second highest dose

EXPERIMENTAL

Drug: ASP1240

Arm L: ASKP1240 highest dose

EXPERIMENTAL

Drug: ASP1240

Arm M: Placebo

PLACEBO COMPARATOR

Sodium Chloride solution

Drug: Placebo

Interventions

ASP1240 DRUG

infusion

Arm A: ASKP1240 lowest dose; Arm B: ASKP1240 second lowest dose; Arm C: ASKP1240 third lowest dose; Arm D: ASKP1240 fourth lowest dose; Arm E: ASKP1240 fifth lowest dose; Arm F: ASKP1240 middle dose; Arm G: ASKP1240 sixth highest dose; Arm H: ASKP1240 fifth highest dose; Arm I: ASKP1240 fourth highest dose; Arm J: ASKP1240 third highest dose; Arm K: ASKP1240 second highest dose; Arm L: ASKP1240 highest dose

Placebo DRUG

infusion

Also known as: Sodium Chloride solution

Arm M: Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Kyowa Kirin Co., Ltd.: collaborator

Study Sites (1)

Parexel

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Interventions

Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: March 29, 2012
• Study Start: January 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: December 10, 2012

Record last verified: 2012-12

Locations

US (1)