A Multiple Dose Escalation Study of ASKP1240 in Subjects With Moderate to Severe Plaque Psoriasis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Kyowa Hakko Kirin Company, Limited
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01585233
First received: April 24, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Psoriasis
Drug: ASKP1240
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetics of ASKP1240: Area under the curve 0-336 (AUC336 ) [ Time Frame: Day 1 to Day 113 (12 visits) ] [ Designated as safety issue: No ]
  • Pharmacokinetics of ASKP1240: Maximum Concentration (Cmax) [ Time Frame: Day 1 to Day 113 (12 visits) ] [ Designated as safety issue: No ]
  • Pharmacodynamic variable: CD40 receptor occupancy on peripheral blood B cells [ Time Frame: Day 1 to Day 113 (12 visits) ] [ Designated as safety issue: No ]
  • Characterize safety profile of ASKP1240 through adverse event reporting, vital signs, clinical laboratory evaluations, physical examinations and 12-lead electrocardiograms (ECGs) [ Time Frame: 113 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change from baseline to 8 weeks in Psoriasis Area Severity Index (PASI) score [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline to 8 weeks in Physicians Static Global Assessment (PSGA) score [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • Proportion of Subjects Achieving Treatment Success [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Success of the treatment of psoriasis is defined as a score of 1 (almost clear) or 0 (clear) as measured by the PSGA

  • Mean change from baseline to 8 weeks in % Body Surface Area (BSA) [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
  • Cytokine Concentration [ Time Frame: Day 1 to Day 113 (9 visits) ] [ Designated as safety issue: No ]
  • Anti-ASKP1240 antibodies [ Time Frame: Day 1 to Day 113 (8 visits ) ] [ Designated as safety issue: No ]
  • Lymphocyte subset quantitation [ Time Frame: Day 1 to Day 113 (9 visits) ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2012
Estimated Study Completion Date: March 2015
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
ASKP1240 lowest dose
Drug: ASKP1240
Intravenous
Experimental: Cohort 2
ASKP1240 low dose
Drug: ASKP1240
Intravenous
Experimental: Cohort 3
ASKP1240 high dose
Drug: ASKP1240
Intravenous
Experimental: Cohort 4
ASKP1240 highest dose
Drug: ASKP1240
Intravenous
Placebo Comparator: Placebo Drug: Placebo
Intravenous

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585233

Locations
Australia, Queensland
Specialist Connect
Brisbane, Queensland, Australia, 4102
Australia, Victoria
CMAX
Adelaide, Victoria, Australia, 5000
Epworth Hospital
Richmond, Victoria, Australia, 3121
Australia, Western Australia
Linear Research
Nedlands, Western Australia, Australia, 6009
Canada, New Brunswick
Durondel C.P. Inc, The Dermatology Clinic
Moncton, New Brunswick, Canada, E1C 8X3
Canada, Newfoundland and Labrador
New Lab Clinical Research
St. John's, Newfoundland and Labrador, Canada, A1C 2H5
Canada, Ontario
Ultranova Skincare
Barrie, Ontario, Canada, L4M 6L2
K. Papp Clinical Research
Waterloo, Ontario, Canada, N2J 1C4
Canada, Quebec
Innovaderm Research, Inc.
Montreal, Quebec, Canada, H2K 4L5
New Zealand
Auckland Clinical Studies
Auckland, New Zealand, 1010
Christchurch Clincial Studies Trust, Ltd.
Christchurch, New Zealand, 8011
P3 Research, Tauranga
Tauranga, New Zealand, 3110
P3 Research, Wellington
Wellington, New Zealand, 6021
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Kyowa Hakko Kirin Company, Limited
Investigators
Study Director: Senior Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01585233     History of Changes
Other Study ID Numbers: 7163-CL-0107
Study First Received: April 24, 2012
Last Updated: June 23, 2014
Health Authority: Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Ministry of Health

Keywords provided by Astellas Pharma Inc:
Moderate Psoriasis
Severe Psoriasis
Skin disease
ASKP1240
CD40 antigen
Anti-CD40 monoclonal antibody

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on August 18, 2014