E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe psoriasis that are resistent to etanercept ab initio or have failed 24 weeks of treatment with etanercept |
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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 of infliximab therapy (infusion of 5 mg/kg at weeks 0, 2, 6, 14, 22), evaluated through PASI 75 (defined as the proportion of subjects achieving at least a 75% PASI – Psoriasis Area and Severity Index - improvement from the baseline) at visit 5 (week 10). In those patients in whom the previous treatment with etanercept was not successful, according to inclusion criteria. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of infliximab through the following parameters: • PASI (Psoriasis Area and Severity Index) 50, 75,90 and 100 • BSA (Body Surface Area Affected) • SAPASI (Self-Administered PASI) • VAS (Visual Analog Scale) to assess itch intensity
To assess the impact of psoriasis and the treatment with Infliximab on the quality of life through:
• DLQI (Dermatology Quality of Life Index) • SKINDEX 29
To evaluate the tolerance and safety of infliximab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 psoriasis at least 6 months prior to Screening (subjects with concurrent psoriatic arthritis may be enrolled).
3. Subjects resistant or patient who must have failed 24 weeks of treatment with etanercept. (Definition of resistant patient: patient who has not modified or presents an increase in his PASI score or BSA affected after 12 weeks of etanercept treatment. Definition of patient failure: patient who has not reached PASI 75 or presents BSA ≥ 10 at Screening visit (V1) after 24 weeks of etanercept treatment.
4. Subjects who has not reached PASI 75 at Screening visit (V1) after 24 weeks of etanercept treatment or resistant ab initio to etanercept.
5. Subjects must agree to avoid prolonged sun exposure or artificial ultraviolet light sources during the study.
6. Subjects must comply with the requirements of the screening and diagnosis Tubercolosis Skin Test (according to procedure described in section 8.12 of the present protocol). Subjects are considered eligible according to the following 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. Two negative tuberculin skin tests; one positive tuberculin skin test in association with appropriate treatment for latent TB initiated prior to or simultaneously with the first administration of study medication
7. Subjects must have had a chest x-ray (posterior-anterior and lateral) at visit 1 or within 3 months prior to vist 1 with no evidence of malignancy, infection or fibrosis.
8. Subjects’ Screening clinical laboratory tests must be within the following parameters:
a. Hemoglobin ≥10 g/dL b. White blood cells ≥3.5 x 109/L c. Neutrophils ≥1.5 x 109/L d. Platelets ≥100 x 109/L e. Serum creatinine <1.5 mg/dL f. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase ≤1.5 x upper limit of normal range g. Total bilirubin ≤1.5 x upper limit of normal range
9. Subjects must be free of any clinically significant disease (other than psoriasis or psoriatic arthritis) that would interfere with the study evaluations.
10. Subjects must be willing to participate to the study and to adhere to study procedures by signing the written informed consent.
11. Women of childbearing potential and all men must be using adequate birth control measures and must continue using such measures until 6 months after receiving the last dose of study medication.
12. Female subjects of childbearing potential must have a negative serum pregnancy test (beta-hCG) at visit 1 and a negative urine pregnancy test at visit 2. |
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E.4 | Principal exclusion criteria |
1. Subjects who achieved PASI 75 or who have had BSA < 10 after 24 weeks of etanercept treatment.
2. Subjects who have current drug-induced psoriasis (f.i., a new onset of psoriasis or an exacerbation of psoriasis due to iatrogenic factors).
3. Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period or during the 6 months after receiving the last dose of study medication.
4. Subjects previously treated with infliximab.
5. Subjects who are currently taking or have taken the following drugs within the specified time frame prior to Screening (see Section 6.2):
a. any live or attenuated virus or bacterial vaccinations received within 3 months prior to visit 1
b. any systemic medications/treatments that could affect psoriasis or clinical evaluations within 4 weeks prior to visit 1.
c. lithium within 4 weeks prior to visit 1
d. any topical medications/treatments that could affect psoriasis or PASI evaluations within 2 weeks prior to visit 1. The only allowed treatments are emollient/moisturizing lotion and shampoos containing salicylic acid. Subjects should not use these topical agents the day prior to study visit. Non-medicated shampoos may be used on the day of a visit.
6. Subjects who have a concomitant diagnosis of congestive heart failure (CHF), including medically-controlled and or asymptomatic subjects.
7. Subjects who have a history of chronic or recurrent infectious disease, including: chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic cystitis), open skin wounds/ulceration that are draining or infected.
8. Subjects who have had or have a serious infection (eg, hepatitis, pneumonia or pyelonephritis), or have been hospitalized or received intravenous (IV) antibiotics for this infection during the 2 months prior to visit 1.
9. 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 Visit 1.
10 Subjects who have or have had a Herpes zoster infection within 2 months prior to visit 1.
11. Subjects who are known to be infected with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV).
12. Subjects who have a history of any clinically significant AEs (including allergic reactions) to murine or chimeric proteins or human/murine recombinant products.
13. Subjects who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
14. Subjects who have a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis.
15. Subjects who have current signs and symptoms or history of systemic lupus erythematosus.
16. Subjects who have a transplanted organ (with the exception of a corneal transplant >3 months prior to visit 1).
17. 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.
18. Subjects who have any 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).
19. Subjects who are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
20. Subjects who are known to have had a substance abuse (drug or alcohol) problem within the previous 3 years.
21. Subjects who have a history of any clinically significant adverse reactions (including allergic reactions) to paracetamol/acetaminophen or histamine H1 receptor antagonist.
22. 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.
23. Subjects who have used any investigational drugs within 4 weeks of Screening.
24. Subjects who are participating in any other clinical study.
25. Subjects who are staff personnel directly involved with this study.
26. 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 study is the PASI 75 response rate (PASI 75 is defined as the proportion of subjects achieving a ≥75% improvement in PASI from Baseline value) at visit 5 (Week 10). |
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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 | No |
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 |
|
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) | No |
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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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
|
The subject is considered to have completed the study EITHER upon the completion of the last protocol-specified visit or contact (eg. phone contact with the principal investigator or qualified designee), OR upon receiving the last dose of the study medication, if that occurs after the last protocol-specified visit or contact. |
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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 | 6 |
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 | 6 |