E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Plaque Psoriasis |
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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 | 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 |
To assess the efficacy and safety of adalimumab in combination with topical psoriasis treatment, calcipotriol/betamethasone vs. adalimumab in combination with matching vehicle in subjects with moderate to severe chronic plaque psoriasis. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is ≥ 18 years of age. 2. Subject has a diagnosis of chronic plaque psoriasis with disease duration of at least 6 months since diagnosis. Subjects with concomitant psoriasis palmaris and plantaris will be permitted into this study. 3. Subject must have been treated and failed to respond to, or has a contraindication to, or is intolerant to at least two different systemic therapies, one of which must be cyclosporine, or methotrexate or oral PUVA. 4. Subject must fulfill at least two of the following three Psoriasis severity criteria: ● PASI ≥ 10 ● Affected Body Surface Area (BSA) ≥ 10% ● Dermatology Life Quality Index (DLQI) ≥ 10 5. Female subject is either not of childbearing potential, defined as postmenopausal (at least one year since last menses) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion. ● Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD) ● Contraceptives (oral, parenteral, patch) for three months prior to study drug administration) ● A vasectomized partner 6. Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Baseline. 7. Subject is judged to be in good general health by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, CXR, and 12-lead electrocardiogram (ECG) performed at Screening. 8. Subject must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections. 9. Subject has voluntarily signed and dated an informed consent form prior to any study related procedure and is willing to comply with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 10. Subject has a negative PPD test (or equivalent) and CXR (PA and lateral view) at screening. If the subject had a positive PPD test (or equivalent) and/or CXR (PA and/or lateral view), the subject must have had one of the following: ● Prophylactic treatment initiated prior to administration of study drug; however the course of prophylaxis need not be completed prior to the onset of study drug. Prophylactic treatment will be according to Appendix D (United States Centers for Disease Control [CDC] recommended preventive therapy for TB) or per local guidelines as approved by the Abbott Study Physician. ● Subject has documented prophylactic treatment for TB in the past and does not need to repeat this treatment or TB prophylaxis is ongoing.
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E.4 | Principal exclusion criteria |
1. Subject has previous exposure to adalimumab. 2. Subject has been treated with systemic corticosteroids (oral or parenteral) 4 weeks (28 days) or topical corticosteroids 2 weeks (14 days) prior to Baseline. Inhaled corticosteroids for stable medical conditions are allowed. 3. Subject received topical treatment with calcipotriol or calcipotriol/betamethasone (Daivobet®) within 2 weeks (14 days) prior to Baseline. 4. Subject with known overexposure to PUVA or UVB. 5. Subject received a previous biologic agent within the following washout period: ● Etanercept received < 3 weeks (21 days) before Baseline ● Infliximab received < 8 weeks (56 days) before Baseline ● Efalizumab received < 6 weeks (42 days) before Baseline ● Abatacept (Orencia) received < 65 days before Baseline. 6. Subject has been treated with any investigational drug within one month (30 days) or five half-lives (whichever is longer) prior to Baseline. 7. Subject has other active skin diseases or skin infections (bacterial, fungal, viral or parasitic) or skin manifestations (rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skinveins ichthyosis, ulcers, wounds, perianal and genital pruritus), that may interfere with evaluation of psoriasis. 8. Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, recent cerebrovascular accidents, and any other condition, which in the opinion of the investigator, would put the subject at risk by participation in the study. 9. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal, or liver disease (e.g., fibrosis, cirrhosis, hepatitis B or C), or NYHA class 3 or 4 congestive heart failure. 10. Subject has history of neurologic symptoms suggestive of CNS demyelinating disease and/or diagnosis of CNS demyelinating disease. 11. Subject has history of any cancer or lymphoproliferative disease. 12. Subject has a history of listeriosis, histoplasmosis, untreated or inadequately treated TB, persistent chronic infections, or 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 1st adalimumab dose. 13. Subject is known to have immune deficiency, history of HIV, or is immunocompromised. 14. Female subject who is pregnant or breast-feeding or has positive serum pregnancy test at screening or positive urine pregnancy test at Baseline or considering becoming pregnant during the study or within 150 days after the last dose of adalimumab. 15. Subject has a history of clinically significant drug or alcohol usage in the last year. 16. Known positive Hepatitis B or C serology indicative of previous or current infection. 17. Screening clinical laboratory analyses show any of the following abnormal hepatic laboratory results: ● Aspartate transaminase (AST) or alanine transaminase (ALT) > 2x the upper limit of normal (ULN). ● Serum total bilirubin ≥ 1.5 mg/dL (≥ 26 micromol/L) 18. Subjects with known hypersensitivity to the constituents of study drugs (adalimumab, calcipotriol/betamethasone, or matching vehicle). 19. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study and not able to comply with the study protocol. 20. Subject has a calcium metabolism disorder.
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E.5 End points |
E.5.1 | Primary end point(s) |
The comparison of the proportion of subjects with a PASI75 at Week 16 Arm 1 (adalimumab + calcipotriol/ betamethasone) vs. Arm 2 (adalimumab + vehicle calcipotriol/betamethasone). |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | 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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The date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is later. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |