E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Chronic Plaque Psoriasis |
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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 | 14.1 |
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 |
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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 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of a personally signed/dated informed consent document.
2. Be at least 18 years of age.
3. Have had a diagnosis of plaque type psoriasis for at least 12 months prior to first dose of study drug.
4. Have a PASI score of 12 or greater AND a PGA score of 3 (“moderate”) or 4 (“severe”) and plaque-type psoriasis covering at least 10% of total body surface area at Baseline/Day 1.
5. Considered by investigator to be candidate for plaque psoriasis systemic therapy or phototherapy (either naïve or history of previous treatment) and to have failed to respond to, or who have a contraindication to, or are intolerant to at least one conventional plaque psoriasis systemic therapy (including cyclosporine, methotrexate, or psoralen plus ultraviolet A light).
6. Sexually active women of childbearing potential are required to use adequate contraceptive methods. No specific contraceptive measures are required in male subjects, unless required according to the etanercept approved local product labeling.
7. 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 or, if unavailable or indeterminate upon retest, a Mantoux/Purified Protein Derivative (PPD) tuberculin skin test using 5 tuberculin units per 0.1 mL (5 TU PPD) result of <5 mm of induration, performed at or within the 3 months prior to a given Screening visit.
• Chest radiographs, taken at or within the 3 months prior to a given Screening visit, without changes suggestive of active TB infection;
• 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.
• 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.
8. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other UV light sources.
9. 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.
10. If received any of the following treatment regimens, for any reason, are eligible providing the following minimum washout criteria are observed:
• Must be discontinued for at least 12 weeks prior to first dose of study drug:
a. Any investigational or experimental therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid arthritis;
Exception: Investigational biologics should be discussed with the Pfizer Medical Monitor (or designee) to confirm period of discontinuation required.
b. Ustekinumab.
• Must be discontinued for at least 8 weeks prior to first dose of study drug:
a. Adalimumab;
b. Infliximab;
c. Alefacept.
• Must be discontinued for at least 4 weeks prior to first dose of study drug:
a. Systemic treatments other than biologics that could affect psoriasis, eg, oral or injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold;
b. Psoralen+UVA phototherapy.
• Must be discontinued for at least 2 weeks prior to first dose of study drug:
c. Topical treatments that could affect psoriasis, eg, corticosteroids, tars, keratolytics, anthralin, vitamin D analogs, and retinoids;
Exceptions – the following topical treatments are allowed: non medicated emollients for use over the whole body; low or least potent (Class 6 or 7) topical corticosteroids for the palms, soles, face, and intertriginous areas only; tar and salicylic acid preparations for the scalp only, and shampoos free of corticosteroids for the scalp only;
d. UVB (narrowband or broadband) phototherapy.
11. Are candidates for etanercept according to the approved local product labeling.
12. Have the ability to store the injectable study drug at 2°C to 8°C and to self-administer the injectable study drug or, alternatively, willing and able to attend clinic visits at the study site for twice weekly study drug injections. |
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E.4 | Principal exclusion criteria |
1. Have nonplaque psoriasis, eg, erythrodermic, guttate, or pustular psoriasis, with the exception of nail psoriasis which is allowed.
2. Have skin conditions that would interfere with psoriasis evaluation.
3. Have drug induced psoriasis, eg, a new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarials or lithium or plan initiation of, or changes to, these medications within 2 weeks prior to randomization or during the study.
4. Are taking or require oral or injectable corticosteroids.
5. The following laboratory values during Screening visit(s):
a. Hemoglobin <11.0 g/dL or hematocrit <30%;
b. White blood cell count <3.0x10 to the power of 9/L;
c. Absolute neutrophil count of <1.5x10 to the power of 9/L;
d. Platelet count <100x10 to the power of 9/L;
e. Estimated Glomerular Filtration Rate (GFR) <40 mL/min based on the Cockcroft Gault calculation or serum creatinine greater than 1.5 times the upper limit of normal (ULN);
f. Aspartate aminotransferase or alanine aminotransferase values more than 2xULN;
g. Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study.
6. Women who are pregnant or lactating, or planning pregnancy during the study.
7. History of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
8. History of lymphoproliferative disorder, lymphoma, leukemia, or signs/symptoms suggestive of lymphatic disease.
9. History of disseminated herpes zoster or herpes simplex, or recurrent localized, dermatomal herpes zoster.
10. History of infection requiring hospitalization, parenteral antimicrobial therapy, or judged to be clinically significant by the investigator within 6 months prior to first dose of study drug.
11. History of infection requiring antimicrobial therapy within 2 weeks prior to first dose of study drug.
12. Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to first dose of study drug, or expects to be vaccinated with these vaccines anytime up to 6 weeks following the last dose of study drug.
13. Any prior treatment with non B cell specific lymphocyte depleting agents/therapies. 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.
14. Have previously been treated with efalizumab or etanercept.
15. Have previously participated in any study of CP 690,550 administered orally.
16. Have failed any tumor necrosis factor inhibitor (TNFi) treatment for either lack of efficacy or a TNFi mechanism related adverse event.
17. 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.
18. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery.
19. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug.
20. Screening or Baseline ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results.
21. Have known immunodeficiency or first degree relative with a hereditary immunodeficiency.
22. History of malignancies with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
23. Have undergone significant trauma or major surgery within 1 month prior to Screening.
24. Require treatment with prohibited concomitant medication including prohibited dietary supplements or received a prohibited concomitant medication/dietary supplement within 7 days or 5 half lives (whichever is longer) prior to the first dose of study drug.
25. Known to be infected with HIV, hepatitis B or C viruses.
26. Have participated in other studies using an investigational or experimental therapy or procedure within 4 weeks or 5 half lives (whichever is longer) prior to the first dose of study drug. Investigational or experimental therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid arthritis must be discontinued for at least 12 weeks prior to first dose of study drug. Subjects cannot participate in studies of other investigational or experimental therapies or procedures at any time during their participation in this study. |
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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
- Incidence and severity of adverse events over 12 weeks of treatment
- Incidence of clinical laboratory abnormalaities and change from baseline in clinical laboratory values over 12 weeks of treatment.
-The pharmacokinetics of CP-690,550 (5 mb bid and 10 mg bid) and etanercept (50 mg) at week 8. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 |
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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 | 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.8.2.4 | 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 |
France |
Germany |
Hong Kong |
Hungary |
Israel |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Singapore |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
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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
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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. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |