| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to Severe Chronic Plaque Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| 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 efficacy of CP-690,550 (5 mg BID and 10 mg BID) versus etanercept (50 mg BIW) and placebo for the reduction in severity of plaque psoriasis after 12 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy;
• Efficacy as measured by the Psoriasis Area and Severity Index 75 (PASI75) response, ie, the proportion of subjects achieving at least a 75% reduction in PASI relative to baseline;
• Efficacy as measured by the Physician’s Global Assessment (PGA) response, ie, the proportion of subjects achieving a PGA of “clear” or “almost clear”;
• To evaluate the safety and tolerability of CP-690,550 (5 mg BID and 10 mg BID) over 12 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. |
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| E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of CP-690,550 (5 mg BID and 10 mg BID) versus placebo for the reduction in severity of plaque psoriasis at various timepoints during 12 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy;
• To evaluate the efficacy of CP-690,550 (5 mg BID and 10 mg BID) versus placebo for the reduction in pruritis at various timepoints during 12 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy;
• To evaluate the effects on patient reported outcome (PRO) measures during 12 weeks of treatment with CP-690,550 (5 mg BID and 10 mg BID) versus placebo at various timepoints in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or legal representative) has been informed of all pertinent aspects of the trial.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Be at least 18 years of age at time of informed consent.
4. Have had a diagnosis of plaque type psoriasis (psoriasis vulgaris) for at least 12 months prior to first dose of study drug.
5. Have a PASI score of 12 or greater AND a PGA score of 3 (“moderate”) or 4 (“severe”) at Baseline/Day 1 (prior to first dose of study drug).
6. Have plaque-type psoriasis covering at least 10% of total body surface area (BSA) at Baseline/Day 1.
7. Considered by dermatologist investigator to be a candidate for systemic therapy or phototherapy of psoriasis (either naïve or history of previous treatment) based on etanercept local label.
8. Considered by dermatologist investigator to have failed to respond to, or who have a contraindication to, or are intolerant to at least one conventional systemic therapy for the treatment of plaque psoriasis (including, but not limited to, cyclosporine, methotrexate, or psoralen plus ultraviolet A light [PUVA]).
9. Sexually active women of childbearing potential are required to use highly effective contraceptive methods during participation in this study. No specific contraceptive measures are required in male subjects during study participation, unless required according to the etanercept approved local product labeling. (Further description of the requirements and a list of contraceptives considered effective and acceptable for use in this study will be found in Section 4.4.7.)
10. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by all of the following:
• A negative QuantiFERON® TB Gold (QFT G) In Tube test performed at or within 3 months prior to a given Screening visit. If QFT testing is unavailable or indeterminate upon retest, a Mantoux/Purified Protein Derivative (PPD) tuberculin skin test can be performed at or within the 3 months prior to a given Screening visit. The Mantoux PPD tuberculin test consists of intracutaneous injection of PPD according to local standards in 0.1 mL of solution on the volar aspect of the forearm, using a short beveled 26 or 27 gauge needle. The test is positive according to local standard 48 to 72 hours after injection (evaluation by a health care professional in 48 to 72 hours must be performed). A negative Mantoux PPD tuberculin test is required to meet the inclusion criterion.
• Chest radiographs, taken at or within the 3 months prior to a given Screening visit, without changes suggestive of active TB infection as determined by a qualified radiologist;
• No history of either untreated or inadequately treated latent or active TB infection;
• If a subject has previously received an adequate course of therapy for either latent (9 months of isoniazid in a locale where rates of primary multi drug TB resistance are <5 % or an acceptable alternative regimen) or active (acceptable multi drug regimen) TB infection, neither a QFT G test nor a PPD test need be obtained, but chest radiographs must still be obtained if not performed within 3 months prior to a given Screening visit. Documentation of adequate treatment for TB will be obtained prior to first dose of study drug;
• A subject who is currently being treated for active TB infection is to be excluded;
• A subject who is currently being treated for latent TB infection can only be enrolled with confirmation of current incidence rates of multi drug resistant TB infection in the locale, documentation of an adequate treatment regimen, and with prior approval by the Sponsor.
11. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other ultraviolet light sources during the study.
12. If receiving non prohibited concomitant medications for any reason, must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half lives (whichever is longer) prior to first dose of study drug. Subject must be willing to stay on a stable regimen, as defined in Section 5.5.1.
please refer to protocol for complete list of inclusion criteria
|
|
| E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Currently have non plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis, with the exception of nail psoriasis which is allowed.
2. Have evidence of skin conditions (eg, eczema) at the time of the screening or baseline visit that would interfere with evaluation of psoriasis.
3. Have current drug induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium.
4. If planned initiation of, or changes to, concomitant medication that could affect psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs or lithium) are to occur within 2 weeks prior to randomization and/or during the study.
5. Cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot discontinue phototherapy (UVB or PUVA).
6. Are taking or require oral or injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids for any condition.
7. The following laboratory values during Screening visit(s):
a. Hemoglobin <11.0 g/dL (<110.0 g/L) or hematocrit <30% (<0.30 v/v);
b. White blood cell count <3.0 x 109/L (<3000/mm3);
c. Absolute neutrophil count of <1.5 x 109/L (<1500/mm3);
d. Platelet count <100 x 109/L (<100,000/mm3);
e. Estimated creatinine clearance <40 mL/min based on the Cockcroft Gault calculation (see Appendix 2) or serum creatinine greater than 1.5 times the upper limit of normal (ULN);
f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values more than 2 times the ULN;
g. Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study.
8. Women who are pregnant or lactating, or planning pregnancy while enrolled in the study.
9. Have current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
10. Have a history of any lymphoproliferative disorder (such as Epstein Barr Virus [EBV] related lymphoproliferative disorder), history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease.
11. Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
12. Have a history of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to first dose of study drug.
13. Have a history of infection requiring antimicrobial therapy within 2 weeks prior to first dose of study drug (for exception regarding latent TB infection see Inclusion Criterion #10).
14. Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to the first dose of study drug, or expects to be vaccinated with these vaccines during treatment or during the 6 weeks following the last dose of study drug. For further information regarding avoidance of household contacts who may be vaccinated see Section 4.4.1.
15. Any prior treatment with non B cell specific lymphocyte depleting agents/therapies (eg, alemtuzumab [CamPath], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc). Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to first dose of study drug and have normal CD19/20+ counts by FACS analysis.
16. Have previously been treated with efalizumab (Raptiva).
17. Have previously participated in any study of CP 690,550 administered orally.
18. Have previously been treated with etanercept (Enbrel) for any reason.
19. Have failed any tumor necrosis factor inhibitor (TNFi) treatment for either lack of efficacy or a TNFi mechanism related adverse event.
20. Are contraindicated for treatment with etanercept, or meet warnings and precautions for use specifications in accordance with the approved local product label, including subjects with multiple sclerosis or any other demyelinating disease and subjects meeting the New York Heart Association Class III and Class IV Congestive Heart failure:
• Class III: patients with marked limitation of activity; they are comfortable only at rest;
• Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.
please refer to protocol for complete list of exclusion criteria
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints
• Physician’s Global Assessment (PGA) response ie, the proportion of subjects achieving a PGA of “clear” or “almost clear”, at Week 12;
• Psoriasis Area and Severity Index 75 (PASI75) response ie, the proportion of subjects achieving at least a 75% reduction in Psoriasis Area and Severity Index relative to baseline, at Week 12.
Safety Endpoints
• Incidence and severity of adverse events over 12 weeks of treatment;
• Incidence of clinical laboratory abnormalities and change from baseline in clinical laboratory values over 12 weeks of treatment;
• Incidence of clinically significant changes in physical examination from baseline over 12 weeks of treatment;
• Incidence of vital sign (blood pressure and heart rate) abnormalities and change from baseline in vital sign measures over 12 weeks of treatment;
• Incidence of electrocardiogram (ECG) abnormalities and change from baseline in ECG measures over 12 weeks of treatment;
• Summary of adjudicated cardiovascular endpoints;
• Summary of central laboratory pathologist over read malignancy events.
Pharmacokinetic (PK) Endpoints
• The pharmacokinetics of CP-690,550 (5 mg BID and 10 mg BID) and etanercept (50 mg BIW) at Week 8. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- PGA response at Week 2,4 and 8
- Proportion of subjects in each PGA category at various timepoints through week 12
- PAS175 response at week 2, 4 and 8
Actual and change from baseline in PASI and PASI component scores at various timepoints through week 12
- Proportion of subjects achieving at least a 50% and 90% reduction in PASI relative to baseline (PAS150 and PAS190 respectively) at various timepoints through week 12
- Time to PAS150 and PAS175 responses
- Proportion of subjects with a PASI score >=125% of the baseline PASI score at various timepoints through week 12
- Actual and change from baseline in the itch Severity item (ISI) score at various timepoints through week 12
- Actual and change from baseline on the Dermatology Life Quality Index (DLQI) score at various timepoints through week 12
- Other patient reported outcome (PRO) measures to be assessed at various timepoints through Week 12, including:
• Short Form 36 (Version 2, Acute) (SF 36);
• Patient Global Assessment of Psoriasis (PtGA);
• Patient Satisfaction with Study Medication (PSSM);
• EuroQol 5 Dimensions (EQ 5D);
• Psoriasis Health Care Resource Utilization Questionnaire (Ps HCRU);
• Psoriasis Health Care Resource Utilization Questionnaire (Ps HCRU);
• Psoriasis Quality of Life–12 (PQOL 12).
• The percent change from baseline in PASI at various time
points through
Week 12;
• The actual BSA and percent change from baseline in BSA at
various time points
through Week 12; |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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 |
|
| 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.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 90 |
| 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 | No |
| 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 |
| Argentina |
| Austria |
| Belgium |
| Bosnia and Herzegovina |
| Bulgaria |
| Chile |
| Colombia |
| Croatia |
| Czech Republic |
| Denmark |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Israel |
| Korea, Republic of |
| Netherlands |
| Poland |
| Portugal |
| Singapore |
| Slovakia |
| Spain |
| Sweden |
| Switzerland |
| Turkey |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| End of trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, Clinical Study Application (CTA)) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 15 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 17 |
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