E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult patients with moderate to severe chronic plaque psoriasis -- who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA, -- AND who have been treated with Raptiva (efalizumab) previously, -- AND who developed adverse events (AEs) corresponding to pre-specified newly diagnosed autoimmune disorders OR who developed severe thrombocytopenia.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061664 |
E.1.2 | Term | Autoimmune disorder |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025139 |
E.1.2 | Term | Lupus erythematosus systemic |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047888 |
E.1.2 | Term | Wegener's granulomatosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002817 |
E.1.2 | Term | Antiphospholipid syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040767 |
E.1.2 | Term | Sjogren's syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003827 |
E.1.2 | Term | Autoimmune hepatitis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049046 |
E.1.2 | Term | Autoimmune thyroiditis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003822 |
E.1.2 | Term | Autoimmune haemolytic anaemia NOS |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034697 |
E.1.2 | Term | Pernicious anemia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028417 |
E.1.2 | Term | Myasthenia gravis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018620 |
E.1.2 | Term | Goodpasture's syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018766 |
E.1.2 | Term | Guillain Barre syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043554 |
E.1.2 | Term | Thrombocytopenia |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037153 |
E.1.2 | Term | Psoriasis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) To assess the prevalence of anti-efalizumab positivity in two sub-populations of psoriatic subjects treated with Raptiva® in the framework of the CLEAREST study:
- Subjects developing adverse events (AEs) corresponding to pre-specified newly diagnosed autoimmune disorders including (but not limited to) systemic lupus erythematosus, Wegener’s granulomatosis, antiphospholipid syndrome, Sjögren syndrome, rheumatoid arthritis, multiple sclerosis, Type I diabetes, auto-immune uveoretinitis, auto-immune gut disorders such as Crohn disease or ulcerative colitis, auto-immune vasculitis, auto-immune hepatitis, auto-immune thyroiditis and other endocrine disorders, auto-immune haemolytic anaemia, pernicious anaemia, myasthenia gravis, Goodpasture’s syndrome, Guillain-Barré syndrome.
- Subjects developing severe thrombocytopenia (grade III or IV according to National Cancer Institute – Common Toxicity Criteria for Adverse Events – i.e. platelet count <50,000/mm3)
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E.2.2 | Secondary objectives of the trial |
- To investigate thrombocytopenia mechanism of action in subjects who develop severe thrombocytopenia (defined as platelet count <50,000/mm3) in the context of previous Raptiva® treatment in the framework of the CLEAREST study. For this secondary objective, a control group of psoriasis subjects without severe thrombocytopenia will be included. - To identify genetic profiles associated with drug-induced thrombocytopenia and autoimmune diseases. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: 1) Subject participating to Study 25878 currently treated or having been treated with efalizumab, with the last dose received within 6 weeks before inclusion in this trial. 2) Subject developing during the study 25878 either - A newly diagnosed autoimmune disease (suspected or confirmed) such as systemic lupus erythematosus, Wegener’s granulomatosis, antiphospholipid syndrome, Sjögren syndrome, rheumatoid arthritis, multiple sclerosis, diabetes type I, autoimmune uveoretinitis, autoimmune gut disorders such as Crohn disease or ulcerative colitis, autoimmune vasculitis, autoimmune hepatitis, autoimmune thyroiditis and other endocrine disorders, autoimmune haemolytic anaemia, pernicious anaemia, myasthenia gravis, Goodpasture’s syndrome, and Guillain-Barré syndrome, or - A severe thrombocytopenia defined as grade III or IV according to NCICTCAE criteria – i.e. platelet count < 50,000 mm3 - during routine monitoring or for -cause laboratory evaluation 3) Subject is willing and able to participate in the trial and has provided signed, informed consent. === In addition, for sites participating to the control group, control subjects will be included and must fulfil all the following criteria: 1) Subject participating to Study 25878 2) Absence of clinical signs of severe thrombocytopenia 3) Either currently treated with efalizumab or not (i.e. last dose of efalizumab received more than 6 weeks before study entry) 4) Subject is willing and able to participate in the trial and has provided signed, informed consent.
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E.4 | Principal exclusion criteria |
1) Participation to any interventional clinical study (inclusion in other registry/ observational study is possible) 2) Administration of specific treatment for the current thrombocytopenia before inclusion in the study (e.g. glucocorticosteroids, plasmapheresis, platelet transfusion) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with binding anti-efalizumab antibodies among subjects with newly diagnosed autoimmune disorders and proportion of subjects with binding antiefalizumab antibodies among subjects who develop severe thrombocytopenia.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Control group of psoriasis subjects w/o thrombocytopenia (only for secondary objective) |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For administrative and safety reporting purposes the end of the trial will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all trial sites. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |