A study of patients with plaque psoriasis to compare the efficacy and safety of 2 different doses of CP-690,550 in patients who stop taking CP-690,550 versus patients who keep taking CP-690,550

• Register: EUCTR
• Last refreshed on: 7 April 2014
• Main ID: EUCTR2010-020005-32-BG
• Date of registration: 04/01/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc.235 East 42nd Street, New York, NY 10017
• Public title: A study of patients with plaque psoriasis to compare the efficacy and safety of 2 different doses of CP-690,550 in patients who stop taking CP-690,550 versus patients who keep taking CP-690,550
• Scientific title: A PHASE 3, MULTI-SITE, RANDOMIZED, MIXED-BLIND, PARALLEL-GROUP TREATMENT WITHDRAWAL AND RE-TREATMENT 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: 27/01/2011
• Target sample size: 660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020005-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Mixed Blind: 2 study periods that are dose-blind and 1 study period that is double-blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Argentina, Australia, Brazil, Bulgaria, Canada, Denmark, Finland, Greece, Italy, Netherlands, Slovakia, United Kingdom, 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 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. 6. Have plaque-type psoriasis covering at least 10% of total body surface area at 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 or, if unavailable or indeterminate upon retest a negative Mantoux Purified Protein Derivative (PPD) tuberculin skin test (according to local standard 48 to 72 hours after injection) 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 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 design
Exclusion criteria:
1. Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular; nail psoriasis is allowed. 2. Have skin conditions that would interfere with evaluation of psoriasis. 3. Have drug-induced new onset or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drug, 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 discontinue systemic, topical or photo (UVB or PUVA) therapies for treatment of psoriasis. 6. Are taking or require oral or injectable corticosteroids for any condition. 7. Laboratory values during Screening visit(s): a. Hemoglobin <11.0 g/dL or hematocrit <30%; b. White blood cell count <3.0 x 10 to the power of 9/L; c. Absolute neutrophil count of <1.5 x 10 to the power of 9/L; d. Platelet count <100 x 10 to the power of 9/L; e. estimated creatinine clearance <40 mL/min based on the Cockcroft-Gault calculation or creatinine greater than 1.5 times the upper limit of normal (ULN); f. Aspartate 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 study participation. 8. Women who are pregnant or lactating, or planning pregnancy while enrolled. 9. Have current or recent 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 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 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 the study or during 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 a study of oral 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. A Screening or Baseline ECG that demonstrates 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 hereditary immunodeficiency.

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

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: tofacitinib
Product Code: CP-690,550
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tofacitinib
CAS Number: 540737-29-9
Current Sponsor code: CP-690,550-10
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)

Timepoint(s) of evaluation of this end point: Week 24-40 and Week 28-56.

Primary end point(s): 1. Proportion of subjects maintaining a Psoriasis Area and Severity Index 75 (PASI75) response (at least a 75% reduction in Psoriasis Area and Severity Index relative to baseline/day 1) during the 16 week double blind active or placebo treatment period (CP 690,550 treatment withdrawal; Period B). 2. Proportion of subjects maintaining a Physician’s Global Assessment (PGA) response (PGA of “clear” or “almost clear”) during the 16 week double blind active or placebo treatment period (CP 690,550 treatment withdrawal; Period B). 3. Among subjects who had a >50% reduction of the Visit A4/Week 24 PASI response during CP 690,550 treatment withdrawal, the proportion of subjects achieving a PASI75 response during CP 690,550 re treatment (Period C). 4. Among subjects who had a PGA of “mild”, “moderate”, or “severe” during CP 690,550 withdrawal, the proportion of subjects achieving a PGA response (PGA of “clear” or “almost clear”) during CP 690,550 re treatment (Period C). - Proportion of subjects with rebound (defined as worsening of psoriasis over baseline
[Day 1, Visit A0] value [PASI>125%] or new type of psoriasis [pustular, erythrodermic, as reported on adverse event forms]) during the period between Week 24 (Visit A4) and Week 32 (Visit B2).

Main Objective: -To compare the efficacy responses of CP-690,550 (5 mg BID and 10 mg BID) versus
placebo following 24 weeks of CP-690,550 treatment and subsequent withdrawal of
active treatment at various timepoints during the 16-week double-blind active or
placebo treatment period in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
-To evaluate the regain of efficacy responses of CP-690,550 (5 mg BID and 10 mg
BID) following 4-16 weeks of CP-690,550 treatment withdrawal and subsequent
re-treatment in subjects with moderate to severe chronic plaque psoriasis who are
candidates for systemic therapy or phototherapy.
-To evaluate the safety and tolerability of CP-690,550 (5 mg BID and 10 mg BID) in
subjects with moderate to severe chronic plaque psoriasis who are candidates for
systemic therapy or phototherapy.

Secondary Objective: - To evaluate the efficacy of CP-690,550 (5 mg BID and 10 mg BID) for the reduction in severity of plaque psoriasis at various timepoints during 56 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
- To evaluate the effects of CP-690,550 (5 mg BID and 10 mg BID) on patient reported outcome (PRO) measures at various timepoints during 56 weeks of treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy

Secondary Outcome(s)

Secondary end point(s): Time to PASI75 response during initial CP-690,550 treatment (Period A).
• Time to PGA response during initial CP-690,550 treatment (Period A).
• Time to loss of adequate response, defined as >50% reduction of the Visit A4/Week
24 PASI response during the 16-week double-blind active or placebo treatment period
(CP-690,550 treatment withdrawal; Period B);
• Proportion of subjects with rebound (defined as worsening of psoriasis over baseline
[Day 1, Visit A0] value [PASI>125%] or new type of psoriasis [pustular,
erythrodermic, as reported on adverse event forms]) during the period between Week
24 (Visit A4) and Week 32 (Visit B2).
• Proportion of subjects with worsening of psoriasis over baseline [Day 1, Visit A0]
value (percent change from baseline PASI>125%) or new type of psoriasis (pustular,
erythrodermic, as reported on adverse event forms) during the 16-week double-blind
active or placebo treatment period (CP-690,550 treatment withdrawal; Period B).
• Time to loss of at least 50% of the Visit A4/Week 24 PASI response and loss of PGA
response (PGA of ‘clear’ or ‘almost clear’) during the 16 week double blind active or
placebo treatment period (CP 690,550 treatment withdrawal; Period B).
• Time to regain PASI75 and PGA response (PGA of ‘clear’ or ‘almost clear’) during
CP 690,550 re treatment (Period C).
• The proportion of subjects regaining PASI75 and PGA response (PGA of ‘clear’ or
‘almost clear’) during CP 690,550 re treatment (Period C).
• Time to PASI75 response during CP-690,550 re-treatment (Period C).
Time to PGA response during CP-690,550 re-treatment (Period C).
• PASI75 response at various timepoints through Week 56.
• PGA response at various timepoints through Week 56.
• Actual and change from baseline in PASI and PASI component scores at various
timepoints through Week 56.
• Proportion of subjects achieving at least a 50% and 90% reduction in PASI relative to
baseline (PASI50 and PASI90, respectively) at various timepoints through Week 56.
• Proportion of subjects with a PASI score ?125% of the baseline PASI score at various
timepoints through Week 56.
• Proportion of subjects in each PGA category at various timepoints through Week 56.
• Actual and change from baseline in the Itch Severity Item (ISI) score at various
timepoints through Week 56.
• Actual and change from baseline on the Dermatology Life Quality Index (DLQI)
score at various timepoints through Week 56.
• Other patient reported outcome (PRO) measures to be assessed at various timepoints
through Week 56.
• Short Form-36 (Version 2, Acute) (SF-36);
• Patient Global Assessment of Psoriasis (PtGA);
• EuroQol 5 Dimensions (EQ-5D).

Timepoint(s) of evaluation of this end point: Baseline to Week 24, Week 24-40 and Week 28-56.

Secondary ID(s)

A3921111

2010-020005-32-GB

Source(s) of Monetary Support

Pfizer Inc