| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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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] - Immune System Diseases [C20] |
| 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 & 10 mg BID) versus placebo for the reduction in severity of plaque psoriasis after 16 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
• To evaluate safety and tolerability over 52 weeks of treatment with CP-690,550 (5 mg BID & 10 mg BID) 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 evaluate the onset of efficacy and durability of efficacy of CP 690,550 (5 mg BID and 10 mg BID) for the reduction in severity of plaque psoriasis at various time points during 52 weeks of treatment; To evaluate the efficacy of CP 690,550 (5 mg BID and 10 mg BID) for the reduction in pruritis at various time points during 52 weeks of treatment; To evaluate the pharmacokinetics of CP 690,550 and its relationship with clinical responses (efficacy and safety) during treatment; To evaluate effects on patient reported outcome (PRO) measures during 52 weeks of treatment with CP 690,550 (5 mg BID and 10 mg BID) at various time points in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic or photo therapy. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the study: 1. Evidence of a personally signed and dated informed consent document indicating the subject (or a legally acceptable 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. 6. Have plaque type psoriasis covering at least 10% of total body surface area Baseline. 7. Considered by investigator to be a candidate for systemic therapy or phototherapy of psoriasis (either naïve or history of previous treatment).8. Sexually active women of childbearing potential are required to use adequate contraceptive methods during study participation. 9. 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-G 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 Screening.[Subjects with a history of Bacille Calmette Guérin (BCG) vaccination will be tested with the QFT G test.], 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.10. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other ultraviolet light sources during the study. 11. Non-prohibited concomitant medications, 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. 12. 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 (Stelara®). Must be discontinued for at least 8 weeks prior to first dose of study drug: a. Adalimumab (Humira®); b. Infliximab (Remicade®); c. Alefacept (Amevive®). Must be discontinued for at least 4 weeks prior to first dose of study drug: a. Etanercept (Enbrel®); b. 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; c. Psoralens + UVA phototherapy (PUVA). Must be discontinued for at least 2 weeks prior to first dose of study drug: a. 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, B. UVB (narrowband or broadband) phototherapy. Prior treatment with efalizumab (Raptiva®) is exclusionary. |
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| E.4 | Principal exclusion criteria |
| 1.Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, pustular; nail psoriasis is allowed. 2.Have skin conditions that would interfere with evaluation of psoriasis. 3.Have drug-induced new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium.4.Have planned initiation of or changes to concomitant medication that could affect psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs or lithium) within 2 weeks prior to randomization or during the study. 5.Cannot stop systemic, topical or photo (UVB or PUVA) therapies for psoriasis. 6.Require oral or injectable corticosteroids for any condition. 7.The following laboratory values during Screening visit(s):a. Hemoglobin <11.0g/dL or hematocrit <30%; b.White blood cell count <3.0x10 to power of 9/L (<3000/mm3); c.Absolute neutrophil count of <1.5x10 to power of 9/L (<1500/mm3); d.Platelet count <100x10 to power of 9/L (<100,000/mm3);e. Estimated creatinine clearance <40 mL/min based on the Cockcroft Gault calculation or serum creatinine more than 1.5XULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 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. 8.Women who are pregnant, lactating, or planning pregnancy while enrolled. 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, lymphoma, leukemia or signs and symptoms suggestive of current lymphatic disease. 11.Had a single episode of disseminated herpes zoster or disseminated herpes simplex or a recurrent localized, dermatomal herpes zoster. 12.Had 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.Had infection requiring antimicrobial therapy within 2 weeks prior to first dose of study drug. 14.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 within the 6 weeks following the last dose of study drug. 15.Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies. Subjects who 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 17.Previously participated in any study of CP-690,550. 18.Have any condition possibly affecting oral drug absorption eg, gastrectomy, clinically significant diabetic gastroenteropathy or certain types of bariatric surgery such as gastric bypass. 19.Have a history of alcohol or substance abuse unless in full remission for greater than 6 months prior to first dose of study drug. 20.Have a Screening or Baseline12 lead ECG with clinically relevant abnormalities which may affect subject safety or interpretation of study results. 21.Have a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency. 22.Have any malignancies or a history of malignancies, except adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. 23.Have had significant trauma or major surgery within 1 month prior to Screening. 24.Require treatment with prohibited concomitant medication(s) or have received a prohibited concomitant medication within 7 days or 5 half lives (which ever is longer) prior to the first dose of study drug. 25.Known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C viruses. 26.Have participated in other studies using an investigational therapy or procedure within 4 weeks or 5 half lives (whichever is longer) prior to the first dose of study drug. Any investigational therapy/ 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 therapies or procedures at any time during their participation in this study. 27.Have any other severe medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration. 28.Subjects who are investigational site staff members or who are Pfizer employees directly involved in the conduct of the trial. 29.In the opinion of the investigator or Pfizer medical monitor, will be uncooperative or unable to comply with study procedures. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints
• Physician’s Global Assessment response, ie, the proportion of subjects achieving a PGA of “clear” or “almost clear”, at Week 16.
• Psoriasis Area & Severity Index 75 response, ie, the proportion of subjects achieving at least a 75% reduction in PASI relative to baseline at Week 16.
Safety Endpoints
• Incidence and severity of adverse events over 52 weeks of treatment.
• Incidence of clinical laboratory abnormalities & change from baseline in clinical laboratory values over 52 weeks of treatment.
• Incidence of clinically significant changes in physical examination from baseline over 52 weeks of treatment.
• Incidence of vital sign (blood pressure & heart rate) abnormalities & change from baseline in vital sign measures over 52 weeks of treatment.
• Incidence of electrocardiogram (ECG) abnormalities & change from baseline in ECG measurements over 52 weeks of treatment.
• Summary of adjudicated cardiovascular endpoints.
• Summary of central laboratory pathologist over read of malignancy events.
Pharmacokinetic Endpoints
• Oral clearance (CL/F) & other PK parameters calculated from plasma CP-690,550 concentrations.
Exploratory Endpoints
•The Molecular Profiling Supplement describes potential exploratory endpoints. |
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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 4.
- PASI75 response at Week 4.
- PASI50 response at Week 2.
- Change from baseline in Itch Severity Item (ISI) score at Week 16.
- Change from baseline in Dermatology Life Quality Index (DLQI) total score at Week 16.
- Change from baseline in ISI score at Week 2.
- Change from baseline in DLQI total score at Week 4. |
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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 | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 |
| Canada |
| Colombia |
| Germany |
| Hungary |
| Mexico |
| Poland |
| Serbia |
| Spain |
| Taiwan |
| Ukraine |
| United States |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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