A One-year study to evaluate the effects and safety of CP-690,550 in patients with moderate to severe chronic plaque psoriasis

• Register: EUCTR
• Last refreshed on: 16 March 2015
• Main ID: EUCTR2010-020003-73-DE
• Date of registration: 29/12/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, 10017 USA
• Public title: A One-year study to evaluate the effects and safety of CP-690,550 in patients with moderate to severe chronic plaque psoriasis
• Scientific title: A PHASE 3, MULTI-SITE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF THE EFFICACY AND SAFETY OF 2 ORAL DOSES OF CP-690,550 IN SUBJECTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS
• Date of first enrolment: 31/03/2011
• Target sample size: 826
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020003-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Canada, Colombia, Germany, Hungary, Mexico, Poland, Serbia, Spain, Taiwan, Ukraine, United States

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

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, psori
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Chronic Plaque Psoriasis
MedDRA version: 14.1 Level: PT Classification code 10037153 Term: Psoriasis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Intervention(s)

Product Code: CP-690,550-10
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
Other descriptive name: Tofacitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 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.

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.

Main Objective: • 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.

Timepoint(s) of evaluation of this end point: Week 16 and Week 52

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Week 52

Secondary ID(s)

A3921079

Source(s) of Monetary Support

Pfizer Inc.