Double-blind, Randomised, Placebo-controlled Trial Investigating BIRT 2584 XX in Patients With Moderate/Severe Psoriasis
- Registration Number
- NCT00333411
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 360
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIRT 2584 XX high dose BIRT 2584 XX - BIRT 2584 XX medium dose BIRT 2584 XX - BIRT 2584 XX low dose BIRT 2584 XX - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Achievement of > 75% reduction from baseline in Psoriasis Area and Severity Index (PASI) score (PASI75 ) at 12 weeks 12 weeks
- Secondary Outcome Measures
Name Time Method Other PASI assessments, NPF Psoriasis Score Static Psoriasis Global Assessment (sPGA), Discontinuations of therapy due to lack of efficacy, Relapse and rebound, Dermatology Life Quality Index, Pain Visual Analog Scale for psoriatic arthritis 12 and 24 weeks
Trial Locations
- Locations (39)
Hôpital Dupuytren
🇫🇷Limoges cedex 1, France
Otto-von-Guericke-Universität Magdeburg
🇩🇪Magdeburg, Germany
Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Hôpital Nord
🇫🇷Saint Priest en Jarez cedex, France
CHU - Hôpital Nord
🇫🇷St Priest en Jarez cedex, France
UZ Antwerpen
🇧🇪Edegem, Belgium
Hôpital de L'Archet
🇫🇷Nice, France
Universitätsklinikum Münster
🇩🇪Münster, Germany
Dermatologie Kliniek
🇧🇪Antwerpen, Belgium
Hôpital Saint Louis
🇫🇷Paris cedex 10, France
Universitäts-Hautklinik
🇩🇪Freiburg, Germany
Eastern Canada Cutaneous Research Associates Ltd.
🇨🇦Halifax, Nova Scotia, Canada
Dr. Wayne Carey
🇨🇦Montreal, Quebec, Canada
Amtssygehuset i Gentofte
🇩🇰Hellerup, Denmark
Cardiff University, Dermatology Department
🇬🇧Cardiff, United Kingdom
Royal Free Hospital, Dermatology Department,
🇬🇧London, United Kingdom
Western Infirmary, Department of Dermatology
🇬🇧Glasgow, United Kingdom
Hope Hospital, The Dermatology Centre,
🇬🇧Salford, United Kingdom
Royal South Hants Hospital, Dept of Dermatology
🇬🇧Southampton, United Kingdom
Hôpital Erasme
🇧🇪Bruxelles, Belgium
Innovaderm Research Inc.
🇨🇦Montreal, Quebec, Canada
Odense Universitetshospital
🇩🇰Odense C, Denmark
Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
Marselisborg Centret
🇩🇰Aarhus C, Denmark
Päijät-Hämeen keskussairaala
🇫🇮Lahti, Finland
Hôpital Saint Jacques
🇫🇷Besançon cedex, France
St. Josef-Hospital
🇩🇪Bochum, Germany
Universitätsklinikum an der TU Dresden
🇩🇪Dresden, Germany
Charite, Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
Universitätsklinikum Schleswig-Holstein
🇩🇪Kiel, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Academic Medical Centre
🇳🇱Amsterdam, Netherlands
University Medical Centre Nijmegen St. Radboud West
🇳🇱Nijmegen, Netherlands
Servicio de Dermatología
🇪🇸Madrid, Spain
Karolinska Universitetssjukhuset Solna
🇸🇪Stockholm, Sweden
Aberdeen Royal Infirmary, Department of Dermatology
🇬🇧Aberdeen, United Kingdom
Skin Therapy Research Unit, St John's Inst of Dermatolology
🇬🇧London, United Kingdom
George Eliot Hospital, Dermatology Department
🇬🇧Nuneaton,, United Kingdom