Clinical trial NCT00669916: A Study Comparing AIN457 to Placebo in Subjects With a Diagnosis of Moderate to Severe Stable Plaque Psoriasis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Plaque Psoriasis
Keywords: Plaque psoriasis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-05-01
Enrollment: 36
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: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Mean Score
timeFrame: Baseline, Week 4
measure: Percentage of Participants With Change From Baseline in Investigators Global Assessment (IGA) Score
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Pharmacokinetics of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
timeFrame: Day 182
measure: Pharmacokinetics of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)
timeFrame: Day 182
measure: 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)
timeFrame: Day 182
measure: Pharmacokinetics of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)
timeFrame: Day 182
measure: Pharmacokinetics of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL)
timeFrame: Day 182
measure: Pharmacokinetics of AIN457: Terminal Elimination Half-life (T1/2)
timeFrame: Day 182
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.