Clinical trial NCT01585233: A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Sequential, Multiple Dose Escalation Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: Moderate Psoriasis
Severe Psoriasis
Skin disease
ASKP1240
CD40 antigen
Anti-CD40 monoclonal antibody
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Kirin Co., Ltd.
First posted: 2012-04-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to explore the safety and tolerability of multiple doses of ASKP1240 compared to placebo and determine Pharmacokinetics and Pharmacodynamics in subjects with moderate to severe psoriasis.

Detailed description: Treatment with ASKP1240 or placebo will be over 4 weeks (Baseline/Day 1, Days 15 and Day 29) with 12 weeks of follow-up for a total of 16 weeks.

Eligibility criteria: Inclusion Criteria:

* Subject has a clinical diagnosis of moderate to severe plaque psoriasis for 6 months or longer with at least 5% or greater Body Surface Area (BSA) affected with plaque psoriasis
* Subject must be a candidate for phototherapy and/or systemic therapy
* Subject must agree to avoid prolonged exposure to the sun and avoid the use of tanning booths or other ultraviolet light sources during the study
* Female subject must be either:

  * post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
  * premenarchal prior to Screening, or
  * documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening), or
* if of childbearing potential, must have a negative serum pregnancy test at Screening and if sexually active must be using highly effective contraception. All sexually active subjects will be required to use highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days \[or 5 five half lives of the study drug whichever is longer\] after final study drug administration.
* Female subject must not be lactating and must not be breastfeeding at Screening or during the study period and for 28 days \[or 5 five half lives of the study drug whichever is longer\] after final study drug administration.
* Female subject must not donate ova starting at Screening and throughout the study period and for 28 days \[or 5 five half lives of the study drug whichever is longer\] after final study drug administration.
* Male subject and their female spouse/partners who are sexually active must be using highly effective contraception1 consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 28 days \[or 5 five half lives of the study drug whichever is longer\] after final study drug administration.
* Male subject must not donate sperm starting at Screening and throughout the study period and for at least 28 days \[or 5 five half lives of the study drug whichever is longer\] after final study drug administration.
* Highly effective contraception is defined as:

  * Established use of oral, injected or implanted hormonal methods of contraception.
  * Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  * Barrier methods of contraception: Condom alone or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
* Subject must be willing and able to comply with the study requirements, including prohibited concomitant medication restrictions.
* Waivers to the inclusion criteria will NOT be allowed.

Exclusion Criteria:

* Subject has non-plaque psoriasis (such as guttate, erythrodermic or pustular psoriasis)
* Subject has received treatment with systemic, non-biologic psoriasis therapy or other systemic immunosuppressant including investigational use of an approved agent within the last 30 days or 5 half-lives, whichever is longer, prior to the first dose of study drug
* Subject has ever been treated with efalizumab (Raptiva®)
* Subject has a total B lymphocyte count by flow cytometric determination that is less than the lower limit of normal
* Subject has a hemoglobin, that are below the lower limit
* Subject has a total white count, total lymphocyte count, total neutrophil count or total platelet that are below the lower limit
* Subject has any of the following lab values:

  * ALT ≥ 1.5 x upper limit of normal
  * AST ≥ 1.5 x upper limit of normal
  * Total bilirubin ≥ 1.5 x upper limit of normal
* Subject has previously received ASKP1240 or has participated in a study involving ASKP1240
* Subject has \> 45 body mass index (BMI)
* Subject with a positive Tubercle Bacillus (TB) test who has not previously received adequate antimicrobial therapy for TB or is currently on, or is planned to start TB antimicrobial therapy
* Subject has abnormal chest x-ray indicative of acute or chronic lung disease
* Subject has uncontrolled intercurrent illness, including, but not limited to ongoing or active infection, any clinically significant cardiac disease seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements
* Subject has a history of any malignancy regardless of the location and the time of diagnosis in the last 5 years (including in-situ carcinoma of the cervix, but excluding successfully treated non-metastatic basal cell and squamous cell carcinoma)
* Subject has received live or live attenuated virus vaccinations within the last 30 days prior to first dose of study drug
* Subject has received treatment with another investigational drug within 30 days or 5 half-lives; whichever is longer, prior to the initiation of Screening
* Subject has a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody
* Subject has a history of a positive test for human immunodeficiency virus (HIV) infection
* Subject has received treatment with systemic, biologic psoriasis therapy or other systemic immunosuppressant including investigational use of an approved agent within the last 56 days or 5 half-lives whichever is longer, prior to the first dose of study drug
* Waivers to the exclusion criteria will NOT be allowed.

Primary outcomes:
measure: Pharmacokinetics of ASKP1240: Area under the curve 0-336 (AUC336 )
timeFrame: Day 1 to Day 113 (12 visits)
measure: Pharmacokinetics of ASKP1240: Maximum Concentration (Cmax)
timeFrame: Day 1 to Day 113 (12 visits)
measure: Pharmacodynamic variable: CD40 receptor occupancy on peripheral blood B cells
timeFrame: Day 1 to Day 113 (12 visits)
measure: Characterize safety profile of ASKP1240 through adverse event reporting, vital signs, clinical laboratory evaluations, physical examinations and 12-lead electrocardiograms (ECGs)
timeFrame: 113 Days
Secondary outcomes:
measure: Mean change from baseline to 8 weeks in Psoriasis Area Severity Index (PASI) score
timeFrame: Baseline and 8 weeks
measure: Mean change from baseline to 8 weeks in Physicians Static Global Assessment (PSGA) score
timeFrame: Baseline and 8 weeks
measure: Proportion of Subjects Achieving Treatment Success
timeFrame: 8 weeks
measure: Mean change from baseline to 8 weeks in % Body Surface Area (BSA)
timeFrame: Baseline and 8 weeks
measure: Cytokine Concentration
timeFrame: Day 1 to Day 113 (9 visits)
measure: Anti-ASKP1240 antibodies
timeFrame: Day 1 to Day 113 (8 visits )
measure: Lymphocyte subset quantitation
timeFrame: Day 1 to Day 113 (9 visits)
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Specialist Connect
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: Victoria
city: Richmond
country: Australia
facility: Epworth Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Research
state: Western Australia
city: Moncton
country: Canada
facility: Durondel C.P. Inc, The Dermatology Clinic
state: New Brunswick
city: St. John's
country: Canada
facility: New Lab Clinical Research
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: Ultranova Skincare
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Montreal
country: Canada
facility: Innovaderm Research, Inc.
state: Quebec
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Christchurch
country: New Zealand
facility: Christchurch Clincial Studies Trust, Ltd.
city: Tauranga
country: New Zealand
facility: P3 Research, Tauranga
city: Wellington
country: New Zealand
facility: P3 Research, Wellington
Study officials:
affiliation: Astellas Pharma Global Development
name: Senior Medical Director
role: STUDY_DIRECTOR
References: