| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe plaque Psoriasis |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 11.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | <Manually entered code. Term in E.1.1> |
|
| 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 Efficacy Endpoint for the current study is the PASI-75 response rate at Week 28. The primary objective is to assess the change in efficacy of treatment with infliximab 5 mg/kg every 6 weeks versus infliximab 5 mg/kg every 8 weeks plus methotrexate 7.5 mg/week in a moderate to severe psoriasis population demonstrating an adequate, but suboptimal response, between Week 23 and 50 (inclusive) after starting treatment with infliximab in the observational study P05319, in accordance with either the SPC in the European Union (EU), the product monograph (PM) in Canada, or per label according to local guidelines in all other participating countries. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective includes PASI-50 response, PASI-90 response, PASI 100 response, and raw PASI scores. Additionally DLQI and EuroQoL-5D Health Questionnaire (EQ-5D) at Weeks 0 and 28 or early termination for the infliximab plus methotrexate arm and for the infliximab shortened infusion interval arm will be used to assess QOL. These endpoints will also be summarized by subgroups based on exposure to biologics before entering P05319. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects must have a diagnosis of moderate to severe plaque-type psoriasis and have had participated in Study P05319
2. Subjects must be screened for this study within 8 weeks from their last infliximab infusion in P05319
3. Subjects must be randomized into this study, Study P05315, between Weeks 23 and 50 (inclusive) of Study P05319.
4. Subjects must have demonstrated a ≥25% and <75% improvement in PASI from Baseline of P05319 between Weeks 23 and 50 (inclusive) of the observational study P05319
5. Subjects must be ≥18 years of age
6. Subjects must be candidates for phototherapy or systemic treatment for psoriasis
7. Subjects must have met all the inclusion and not met any of the exclusion criteria for observational study P05319
8. Subjects must be willing and able to provide written informed consent and comply with the requirements of the study
9. Subjects must be willing and able to attend all study visits
10. Women of childbearing potential and all men must agree to use a medically accepted method of contraception prior to entering the study while receiving protocol-specified medication, and for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy, tubal ligation for women, and vasectomy for men). Women of non-childbearing potential (menopausal) do not have to use any contraceptive methods (menopause is defined as the time when there has been no menstrual periods for 12 consecutive months and no other biological or physiological cause can be identified)
11. Women of childbearing potential and men who are not currently sexually active must agree to use a medically acceptable method of contraception should they become sexually active while participating in the study and receiving protocol-specified medication, and for 6 months after stopping the medication
12. Subjects are considered eligible according to the following tuberculosis (TB) criteria:
a. have no history of latent or active TB within 3 months 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 have active and latent TB ruled out prior to the first administration of study medication,
d. prior to or at the time of infliximab induction therapy during study P05319, EITHER:
i. have had negative diagnostic TB test results (interpreted as negative per local standards and laws), OR
ii. have had a newly identified positive TB test result during Baseline in which active or latent TB has been ruled out
13. Subjects’ Screening and Baseline clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) must be within the following parameters:
a. Hemoglobin ≥10 g/dL (≥100 g/L)
b. White Blood Cells (WBC) ≥3.5 x 109 cells/L
c. Neutrophils ≥1.5 x 109 cells/L
d. Platelets ≥100 x 109 cells/L
e. Serum Creatinine <1.5 mg/dL (<133 mol/L)
f. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase, and Gamma-Glutamyltransferase (GGT) all ≤1.5 times upper limit of normal (ULN)
g. Total Bilirubin ≤1 times ULN
14. Subjects must be free of any clinically significant disease (other than psoriasis) that would interfere with the study evaluations
15. Subjects must have had a chest x-ray within 3 months prior to infliximab induction treatment of the observational study P05319, with no evidence of current or previously active TB. If such an x-ray is not available, subjects must have one performed at the Screening visit with a negative outcome (no clinically significant findings) |
|
| E.4 | Principal exclusion criteria |
1. Subjects for whom infliximab is contraindicated or not recommended
2. Subjects who currently have non-plaque forms of psoriasis
3. Subjects who currently have drug-induced psoriasis
4. Subjects who used any therapeutic agent (investigational or approved) targeted at reducing IL-12, IL-17, or IL-23 within the previous 6 months prior to Screening
5. Subjects who have used any investigational drug at any time within the previous 4 weeks prior to Screening
6. Subjects who have used immunosuppressants at any time within the previous 4 weeks prior to Screening
7. Subjects who have used any systemic medications (other than infliximab) that could affect psoriasis or PASI evaluations at any time within the previous 4 weeks prior to Screening
8. Subjects who have used a TNF-reducing agent other than infliximab at any time within the previous 4 weeks prior to Screening
9. Subjects with ongoing serious adverse events (SAEs) or AEs (as per physician discretion) that would prohibit further treatment with infliximab
10. Women who are breastfeeding, pregnant, or intend to become pregnant, and male study subjects with female partners who are breastfeeding, pregnant, or intend to become pregnant
11. Subjects who are staff personnel directly involved with this study
12. Subjects who are family members of the investigational study staff
13. Subjects with a known intolerance to methotrexate or contraindication to methotrexate
14. Subjects with a concomitant diagnosis of congestive heart failure (CHF), including medically controlled asymptomatic subjects
15. Subjects with a history of chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), and recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis) or open, draining, or infected skin wounds or ulcers
16. Subjects who have or have had an opportunistic infection (infection caused by an organism only in a host whose resistance is lowered by other diseases or by drugs, such as cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to Screening
17. Subjects who have or have had a herpes zoster infection within 2 months prior to Screening
18 Subjects who are known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C
19. Subjects who have a history of any clinically significant AEs or intolerance (including allergic reactions) to murine or chimeric proteins or human/murine recombinant products
20. Subjects who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease
21. Subjects who have a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis
22. Subjects who have current signs and symptoms or history of systemic lupus erythematosus
23. Subjects who have a transplanted organ (with the exception of a corneal transplant >3 months prior to Baseline)
24. 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
25. 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 for 1 year prior to Screening)
26. Subjects who are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins
27. 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
28. Subjects who are participating in any other clinical study
29. Subjects who are known to have had a substance abuse (drug or alcohol) problem within the previous 3 years prior to Screening
30. Subjects who have received live virus or bacterial vaccinations within the previous 3 months prior to Screening |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: The Primary Efficacy Endpoint is related to the Primary Trial Objective. The Primary Efficacy Endpoint for the current trial is the PASI-75 response rate at Week 28.
Primary Safety Endpoints: The Primary Safety Endpoints for the current trial include the number of subjects reporting any AEs, the incidence of AEs in specific categories (serious infections, infusion related reactions/hypersensitivity, fatalities, Congestive heart failure, (new) demyelination neurological disorders, hematological conditions and lymphoproliferative disorders/malignancies), and discontinuations due to AEs.
|
|
| 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 | No |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| 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 |
|
| 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 end of the trial is defined as Last patient's last visit |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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