Double-blind, Randomised, Placebo-controlled Trial Investigating BIRT 2584 XX in Patients With Moderate/Severe Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this clinical study is to determine the effectiveness, pharmacokinetics and
      safety of several doses of BIRT 2584 XX (100mg, 300mg and 500mg) taken once daily in the
      treatment of moderate to severe plaque-type psoriasis. This new medicine will be compared to
      a so-called placebo medicine over 12 weeks with a 12 weeks treatment extension possible.
    

Detailed description: 
      The proposed study is a phase 2a/b international multicentre clinical trial. The general aim
      of this study is to investigate the safety and efficacy (clinical proof of concept) of three
      different doses (100 mg, 300 mg, or 500 mg) of BIRT 2584 XX tablets administered orally once
      daily compared to placebo tablets for the treatment of patients with moderate to severe
      plaque-type psoriasis patients who are candidates for systemic treatment or phototherapy.
      This study may also provide dose-finding information for future pivotal studies.

      The response to treatment will be measured for all patients in the study after 12 weeks of
      treatment using the PASI as the primary endpoint, and also the sPGA. Both instruments
      evaluate the clinical severity of plaque-type psoriatic lesions. Training on PASI and sPGA
      assessment will be provided in order to decrease inter-observer variability. The sPGA is thus
      to be validated for future phase 3 trials.

      After 12 weeks of treatment, only those patients with a response equivalent or better than
      PASI50 and with a satisfactory safety experience will enter a 12 week extension of the
      treatment period. The total time of exposure to study drug in this subgroup of patients will
      be 24 weeks. All other study patients will terminate treatment with study drug after 12
      weeks.

      In addition, the durability of remission/response, and the occurrence of any relapse or
      rebound during the treatment with study drug and after the end of treatment will be assessed
      in an 8 weeks follow-up period. The follow-up period is applicable to all study participants
      who have taken at least one dose of study drug. It initiates after the last dose of study
      medication has been taken, irrespective of the duration of the patients actual treatment
      period.

      The trial will use a modified dose-escalation scheme. The randomisation to the 500 mg
      treatment arm will initiate only after a Data Safety Monitoring Board (DSMB) decision on the
      safety of the other treatment arms. An IVRS will be used for randomisation in this trial.

      Ninety (90) patients are required per dose group. With four groups and an overall 1:1:1:1
      randomisation scheme, a total of 360 eligible patients are planned to be randomised to
      treatment.

      Study Hypothesis:

      Psoriasis is a chronic inflammatory disease that leads to skin sores. These skin sores are
      dependent on the rate of growth of the skin which is driven by an underlying corresponding
      degree of local inflammation. The skin inflammation is caused by different cell types that
      move from the blood vessels into the skin. This cell movement is a result of interaction of
      different proteins. One of these proteins is called LFA-1 (Lymphocyte Function Associated
      Antigen 1). LFA-1 is then a promising target for psoriasis therapy. BIRT 2584 XX will block
      the passage of these inflammatory cells from the blood to the skin by blocking LFA-1, and
      thus indirectly block the inflammatory process. BIRT 2584 XX can also block the activation of
      local inflammatory cells, which altogether may reduce the signs and symptoms of psoriasis.

      A dose-dependent effect of BIRT 2584 XX was observed on a set of markers in the blood that
      are believed to correlate with the severity of the inflammatory process leading to psoriasis.

      Comparison(s):

      In this clinical study, BIRT 2584 XX in a dose of 100 mg, 300 mg or 500 mg, or placebo will
      be given once daily. Patients will receive the same treatment throughout the study.

      Patients will have a 1 in 4 chance (25%) of being allocated to placebo treatment. The placebo
      is identical in appearance compared to any one of the three dose groups with BIRT 2584 XX,
      but does not contain any active ingredient. The purpose of a comparison with placebo is to
      ensure a more reliable assessment of the therapeutic effect and of the side effects of BIRT
      2584 XX.
    

Intervention name(s): BIRT 2584 XX; Placebo
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment