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A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00669916
Recruitment Status : Completed
First Posted : May 1, 2008
Results First Posted : April 10, 2015
Last Update Posted : April 10, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 29, 2008
First Posted Date  ICMJE May 1, 2008
Results First Submitted Date  ICMJE January 28, 2015
Results First Posted Date  ICMJE April 10, 2015
Last Update Posted Date April 10, 2015
Study Start Date  ICMJE February 2007
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2015)
  • Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score [ Time Frame: Baseline, Week 4 ]
    The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease) where a reduction in PASI score from baseline indicates improvement. The percentage change was calculated by subtracting the week 4 values from the baseline values.The percentage change was calculated for each entire treatment group (not for each participant). A positive percentage change from baseline indicates improvement.
  • Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score [ Time Frame: Baseline, Week 4 ]
    The IGA is an instrument which captured and categorized the global assessment of all clinical signs and symptoms of disease. The investigator used all available information for the assessment, including subjective information from the participant and (where available) photographs taken at baseline. The IGA categories were clear, almost clear, mild disease, moderate disease, severe disease and very severe disease. This outcome measure shows the percentage of patients who experienced a category change from baseline. Category changes of 1, 2 or 3 indicate improvement.
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2008)
  • This study will have two primary endpoints which are the reduction in PASI score from baseline to 4 weeks of follow-up and the number of responses as determined by an IGA.
  • Efficacy of AIN457 will be evaluated by comparing the coprimary endpoint of the reduction in PASI score between the placebo and treatment arms
Change History Complete list of historical versions of study NCT00669916 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2015)
  • Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
  • Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
  • Pharmacokinetics of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
  • Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
  • Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
  • Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2) [ Time Frame: Day 182 ]
    Blood was drawn for PK analyses at baseline (prior to dosing), end of infusion, 1 hr and 2 hr after infusion, and during office visits in Weeks 1, 2, 3, 4, 5, 6, 8, 12, 16, 20 and 26. The PK samples may have been taken at any time during each office visit, following the day of study drug infusion. This outcome measure shows the mean of all values resulting from each time point outlined above.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2008)
  • To evaluate the safety of AIN457 when administered as a single dose infusion to patients with stable plaque psoriasis
  • To evaluate the population pharmacokinetics of AIN457 when administered as a single dose infusion to patients with stable plaque psoriasis
  • Characterize the binding kinetics of IL-17/AIN457 complex in blood
  • Characterize the pharmacodynamics of AIN457 in a sentinel plaque
  • Conduct exploratory genomic, proteomic and metabolomic studies to identify gene expression patterns, proteins, and metabolites of blood that are associated with treatment response to AIN457.
  • Perform exploratory analysis of soluble protein markers (by multiplex based immunoassay in serum) and, when applicable, exploratory Pharmacogenomic analysis of skin biopsy if clinical and/or histological response has been demonstrated
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis
Official Title  ICMJE Phase 2a Single-Dose, Randomized, Double Blind, Multi-Center, Parallel-Group, Placebo-Controlled Proof of Concept Study to Assess the Efficacy, Safety, Tolerability, and Population Pharmacokinetics of AIN457 in Patients With Stable Plaque-type Psoriasis
Brief Summary This is a two-arm, parallel group, double-blind, placebo-controlled proof-of-concept study comparing 3 mg/kg of AIN457 to placebo. Subjects with a diagnosis of moderate to severe stable plaque psoriasis will be randomized to receive either AIN457 or placebo. AIN457 or placebo will be administered by single infusion at baseline and subjects will be observed for up to 26 weeks following the infusion.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Basic Science
Condition  ICMJE Plaque Psoriasis
Intervention  ICMJE
  • Biological: AIN457
    single infusion of 3 mg/kg
  • Drug: Placebo
    single infusion of placebo
Study Arms  ICMJE
  • Experimental: AIN457
    AIN457A 3mg/kg was administered intravenously as a single dose.
    Intervention: Biological: AIN457
  • Placebo Comparator: Placebo
    Placebo was administered intravenously as a single dose.
    Intervention: Drug: Placebo
Publications * Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group, Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group, Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010 Oct 6;2(52):52ra72. doi: 10.1126/scitranslmed.3001107.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 30, 2008)
36
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2007
Actual Primary Completion Date November 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or females, aged 18-69 at time of consent.
  • Post menopausal or surgically sterile female patients are allowed. Male patients must be willing to use contraception method at least for 3 months following the completion of the study. Women of child-bearing potential will not be allowed to participate.
  • Diagnosis of plaque psoriasis for at least 6 months prior to screening. The patients must meet both of the following criterion:

    1. Coverage of the body surface area (BSA) of 10% or more with plaques
    2. A score of 3 or more on the IGA scale
  • Stable plaque psoriasis at screening and randomization.
  • PASI score of 12 or greater at randomization.
  • Able to communicate well with the investigator, and to understand and comply with the requirements of the study. Understand and sign the written informed consent.
  • Patients must have normal laboratory values for screening laboratory test results of hematological (hemoglobin, WBCs, neutrophils, platelets) and renal (serum creatinine) assessments. For the transaminases, aspartate aminotransferase and alanine aminotransferase, levels 1.5 times the upper limit of normal will be accepted. For the additional hepatic laboratory results (alkaline phosphatase, gamma-glutamyltransferase, bilirubin), patients must have non-clinically significant values.

Exclusion Criteria:

  • Currently have any of the nonplaque forms of psoriasis: erythrodermic, guttate, or pustular.
  • Currently have drug-induced psoriasis (new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium).
  • Men who are planning to initiate a pregnancy while enrolled in the study or for 3 months following completion of the study.
  • Women of child-bearing potential are not allowed in the study.
  • Used any investigational drug within the previous 4 weeks.
  • Recent previous treatment with anti-TNF-α therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus. The following washout period will be required for such patients to be eligible to participate in the trial.

    1. 2 months washout prior to screening for etanercept, adalimumab, or infliximab.
    2. 1 month washout prior to screening for cyclosporine, mycophenolate, tacrolimus, and any systemic immunosuppressants including, but not limited to, methotrexate, azathioprine, 6-thioguanine, mercaptopurine, and hydroxyurea

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00669916
Other Study ID Numbers  ICMJE CAIN457A2102
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP