E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 compare the safety, tolerability and clinical efficacy of adalimumab with placebo and with methotrexate in the treatment of moderate to severe chronic plaque psoriasis over a 16-week period. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects 18 years of age or older who have a diagnosis of psoriasis for at least 12 months and stable moderate to severe chronic plaque psoriasis, as defined by >10% BSA involvement and PASI score >10 at the Baseline (Week 0) visit.Other main inclusion criteria include: Candidate for systemic therapy or photo-therapy and has active psoriasis despite treatment with topical agents. An evaluation for latent tuberculosis infection with a purified protein derivative test (PPD) and CXR. Subjects who have evidence of latent TB infection may participate in the study provided that prophylactic treatment begins before study drug is administered. Women of child bearing potential must have a negative pregnancy test at Screening and Baseline and practice an adequate method of contraception during and for at least 150 days after study completion. Women must be non-lactating and non-breastfeeding. Men must practice an adequate method of contraception during and for at least 90 days after study completion. |
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E.4 | Principal exclusion criteria |
Main exclusion criteria include; Previous systemic anti-TNF therapy. Previous methotrexate therapy. Known history of allergic reaction or significant hypersensitivity to the constituents of either adalimumab, methotrexate, or placebo. Systemic therapy for psoriasis for at least 4 weeks prior to Baseline; except for biologic therapies which must be discontinued at least 12 weeks prior to enrollment. Topical psoriasis therapy for at least 2 weeks prior to Baseline, except for non-corticosteroid shampoos, bland (no alpha or beta hydroxy) emollients and low potency topical corticosteroids on the palms, soles, face, inframammary area, and groin only. Use of tanning beds, excessive sun exposure, or phototherapy (UVB, UVA), for at least 2 weeks prior to Baseline. Use of PUVA for at least 4 weeks prior to Baseline. Use of oral or injectable corticosteroids during the study. Other active skin diseases or skin infections (bacterial, viral, or fungal) that may interfere with evaluation of psoriasis. History of listeriosis, histoplasmosis, untreated TB, persistent chronic infections. Recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit. Immune deficiency, history of HIV or is immunocompromised· Positive Hepatitis B or C (previous infection) Use of anti-retroviral therapy.History of neurologic symptoms suggestive of central nervous system demyelinating disease. History of clinically significant drug or alcohol usage in the last year or cannot maintain an alcohol intake of 30g a day or less throughout the study. History of or active alcoholism, alcoholic liver disease, or other chronic liver disease, including fibrosis, hepatitis and cirrhosis. History of or active renal or hematologic disease. Malignancies other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, or cervical carcinoma in situ. Erythrodermic, generalized pustular, new onset guttate, or medication-related or exacerbated psoriasis.Subject has a poorly controlled medical condition. Investigator considers the subject unsuitable for adalimumab or methotrexate therapy for any reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable in this study is the proportion of subjects achieving clinical response, defined as at least a 75% reduction in PASI score (³ PASI 75 response) at Week 16 relative to the Baseline (Week 0) PASI score.Subjects who do not have PASI assessments at Week 16 will be imputed as non-responders. |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
E.6.12 | Pharmacoeconomic | No |
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) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 13 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 13 |