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 of other systemic therapies including cyclosporin, methotrexate and PUVA |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10037153 |
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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 |
To establish control of moderate to severe chronic plaque psoriasis with efalizumab in patients who have failed to respond to, or who have a contraindication to, or are intolerant of other systemic therapies including cyclosporin, methotrexate and PUVA. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the management of psoriasis events, namely rebound and exacerbation (psoriasis flare-ups) in patients while i) on efalizumab therapy and ii) subsequent to its discontinuation: - Rebound of disease is defined as: worsening of disease in responders as assessed by >125% baseline PASI, or new pustular, erythrodermic, or more inflammatory psoriasis occurring within 2 months of stopping therapy. - Exacerbation of disease is defined as: disease worsening in non responders either during or after treatment, which is more inflammatory in nature, and occurring either within pre-existing plaques, at previously uninvolved sites, or as new morphologies of disease, compared to baseline. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Moderate to severe plaque psoriasis patients who have failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including cyclosporin, methotrexate and PUVA OR Subjects who have completed the CLEAR study IMP24011 and are eligible according to the above criterion and who wish to continue or restart efalizumab therapy. 2. At least 18 years old. 3. For women of childbearing potential and for men whose partner can become pregnant, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study and up to 3 months after the last dose of efalizumab. 4. Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that the consent may be withdrawn by the patient at any time without prejudice to future medical care. 5. Discontinuation of any systemic psoriasis treatment as described in section 6.2.2 of the protocol. No washout period is required for these systemic psoriasis agents prior to starting study and receiving first dose of study drug (efalizumab). 6. Discontinuation of all biologic agents (other than efalizumab) 3 months prior to receiving first dose of study drug (efalizumab). 7. Discontinuation of any investigational drug or treatment 3 months prior to study day 0 as per washout requirements from previous protocol. 8. No primary vaccinations (eg, tetanus, booster, influenza vaccine) for at least 14 days prior to first dose of study drug. 9. The patient must be willing and able to comply with the protocol requirements for the duration of the study. 10. Patients previously treated with efalizumab will be permitted to enter this study, unless they withdrew from this previous therapy due to a lack of efficacy or an adverse event that was deemed related to efalizumab, and that they meet all inclusion criteria and none of the exclusion criteria within the 14 days prior to study day 0.
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E.4 | Principal exclusion criteria |
1. Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis. 2. Patients who have previously been on efalizumab treatment who withdrew due to lack of efficacy or an adverse event. If withdrawal was due to another non-drug reason (vaccination , or infection) then the patient can be included in this study. 3. History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies. 4. History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection. 5. History of opportunistic infections (eg, systemic fungal infections, parasites). 6. Seropositivity for human immunodeficiency virus (HIV). Patients will undergo mandatory testing at screening. Patients who are positive for HIV will be excluded. 7. Pregnancy or breast feeding. 8. WBC count <4.0x109/L or >14.0x109/L. 9. Patient with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count <100,000 cells/L. 10. Seropositivity for hepatitis B or C virus. Patients will undergo testing at screening. Patients who are positive for hepatitis B antigen or hepatitis C antibody will be excluded. 11. History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to study day 0. Chest X-ray (within 3 months prior to SD0) is required for high-risk patients (Protocol, appendix J). Patients with a positive chest X-ray will be excluded. 12. Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Patients with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled. 13. Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year. 14. Any medical condition that, in the judgment of the investigator, would jeopardize the patient’s safety following exposure to study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients achieving a PGA of change (Physician Global Assessment - 7 points score), rated Good, Excellent, or Cleared at week 12. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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End of study will be defined as the date of the final database lock. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |