E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe psoriasis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
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 |
The primary objective of this trial is to assess the efficacy of infliximab therapy (5mg/kg by body weight) compared with methotrexate in adult subjects (aged 18-75 years) diagnosed with moderate to severe plaque-type psoriasis for at least 6 months prior to study screening (subjects with concurrent psoriatic arthritis may also be enrolled). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the trial are to assess the safety of infliximab compared with methotrexate and to assess the quality-of-life in subjects with moderate to severe psoriasis. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The subject must meet ALL of the criteria listed below for entry: 1. Subjects must be ≥18 to 75 years of age at Screening, of either sex, and of any race. 2. Subjects must have had a diagnosis of moderate to severe plaque-type psoriasis at least 6 months prior to Screening (subjects with concurrent psoriatic arthritis may be enrolled). 3. Subjects must have plaque-type psoriasis covering at least 10% of total BSA at Screening and Baseline. 4. Subjects must have a PASI score of 12 or greater at Screening and Baseline (see Appendix 7). 5. Subjects must be candidates for phototherapy or systemic treatment of psoriasis (either naïve or history of previous treatment). 6. Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. 7. Subjects are considered eligible according to tuberculosis (TB) screening criteria: a) Have no history of latent or active TB prior to screening; b) Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; c)Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication; d) Within 1 month prior to the first administration of study medication, either have a negative diagnostic TB test results (defined as 2 negative tuberculin skin tests) OR have a newly identified positive diagnostic TB test result (defined as at least 1 positive tuberculin skin test) during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study medication. 8. Subjects must have had a chest x-ray (posterior-anterior and lateral) within 3 months prior to Screening with no evidence of malignancy, infection, or fibrosis, or current or old active TB. 9. Subjects’ Screening and Baseline clinical laboratory tests (CBC, blood chemistry, and urinalysis) must be within the following parameters: (a) Hemoglobin ≥10 g/dL, (b) White blood cells ≥3.5 x 10 9/L, (c) Neutrophils ≥1.5 x 10 9/L, (d) Platelets ≥100 x 10 9/L, (e) Serum creatinine <1.5 mg/dL (or <133 µmol/L), (f) Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase ≤1.5 x upper limit of normal, and (g) Total bilirubin ≤1 x upper limit of normal. 10. Subjects must be free of any clinically significant disease (other than psoriasis or psoriatic arthritis) that would interfere with the study evaluations. 11. Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules. 12. Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last dose of study medication. 13. Female subjects of childbearing potential must have a negative serum pregnancy test (beta-hCG) at Screening and a negative urine pregnancy test at Baseline. |
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E.4 | Principal exclusion criteria |
The subject will be excluded from entry if ANY of the criteria listed below are met: 1. Subjects who have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular). 2. Subjects who have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium). 3. Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period and the 6 months after study completion. 4. Subjects previously treated with infliximab. 5. Subjects previously treated with MTX. 6. Subjects who are currently taking or have taken the following drugs within the specified time frame prior to baseline: (a) any therapeutic agent targeted at reducing TNF within 3 months, (b) any biologic within 3 months, (c) any live virus or bacterial vaccinations received within 3 months prior to Screening, (d) any systemic medications/treatments that could affect psoriasis or PASI evaluations within 4 weeks, (e) any systemic immunosuppressants within 4 weeks, (f) lithium within 4 weeks, and (g) any topical medications/treatments that could affect psoriasis or PASI evaluation within 2 weeks. The only allowed topical treatments for psoriasis are shampoos (containing tar or salicylic acid only) and topical moisturisers. Subjects should not use these topical agents during the morning prior to a study visit. Non-medicated shampoos may be used on the morning of a visit. 7. Subjects who have a concomitant diagnosis of congestive heart failure (CHF), including medically-controlled asymptomatic subjects. 8. Subjects who have a history of chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin wounds or ulcers. 9. Subjects who have had or have a serious infection (eg, hepatitis, pneumonia or pyelonephritis), or have been hospitalized or received intravenous (IV) antibiotics for an infection during the 2 months prior to Screening. 10. Subjects who have or have had an opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to Screening. 11. Subjects who have or have had a Herpes zoster infection within 2 months prior to Screening. 12. Subjects who are known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C. 13. Subjects who have a history of any clinically significant AEs (including allergic reactions) to murine or chimeric proteins or human/murine recombinant products. 14. Subjects who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease. 15. Subjects who have a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis. 16. Subjects who have current signs and symptoms or history of systemic lupus erythematosus. 17. Subjects who have a transplanted organ (with the exception of a corneal transplant >3 months prior to Screening). 18. Subjects who have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location. 19. Subjects who have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of basal cell carcinoma of the skin that has been treated with no evidence of recurrence). 20. Subjects who are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins. 21. Subjects who are known to have had a substance abuse (drug or alcohol) problem within the previous 3 years. 22. Subjects who have a history of any clinically significant hypersensitivity reaction/adverse reaction (including allergic reactions) to paracetamol/acetaminophen, antihistamine or topical corticosteroids. 23. Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. 24. Subjects who have used any investigational drugs within 4 weeks of Screening. 25. Subjects who are participating in any other clinical study. 26. Subjects who are staff personnel directly involved with this study. 27. Subjects who are family members of the investigational study staff. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the trial is the PASI75 (defined as the proportion of subjects achieving a greater than or equal to 75% improvement in Psoriasis Area and Severity Index) response rate at Week 16. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 5 |