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: EUCTR2010-019988-10-DE
• Date of registration: 27/12/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, 10017
• 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 - OPT Pivotal #1
• Date of first enrolment: 05/04/2011
• Target sample size: 826
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019988-10
• 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

Brazil, Canada, Colombia, Germany, Hungary, Japan, 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:
1. Evidence of a personally signed and dated informed consent document indicating the subject (or a 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 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 highly effective method of contraception during participation in this study and for 28 days after the last dose of assigned treatment.
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
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 screening or baseline visit that would interfere with the 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 or serum creatinine greater than 1.5 times the upper limit of normal (ULN); f. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than 2 times the upper limit of normal (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;
women of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 28 days after last dose.
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.
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 within the 6 weeks following the last dose of study drug.
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 rec

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

Health Condition(s) or Problem(s) studied

CHRONIC PLAQUE PSORIASIS
MedDRA version: 15.1 Level: PT Classification code 10037153 Term: Psoriasis System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

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

Intervention(s)

Product Code: CP-690,550-10
Pharmaceutical Form: Film-coated tablet
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)

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

Main Objective: • 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 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 and 10 mg BID) in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

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 16.
• Psoriasis Area and Severity Index 75 (PASI75) 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 and 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 and heart rate) abnormalities and change from baseline in vital sign measures over 52 weeks of treatment.
• Incidence of electrocardiogram (ECG) abnormalities and 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.

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 treatmentin subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy;
-To evaluate the pharmacokinetics of CP-690,550 and its relationship with clinical responses (efficacy and safety) during treatment in subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
-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 therapy or phototherapy.

Secondary Outcome(s)

Secondary end point(s): -Percent change from baseline in BSA at week 16.
-PASI90 response at Week 16.
-Change from baseline in Dermatology Life Quality Index (DLQI) total score at
Week 16.
-PGA response at Week 4.
-PASI75 response at Week 4.
-Change from baseline in DLQI total score at Week 4.
-Percent change from baseline in Nail Psoriasis Severity Index (NAPSI) at Week 16 in
subjects with nail psoriasis at Baseline.
-Proportion of subjects maintaining PGA response at Week 52 among subjects achieving PGA response at Week 16.
-Proportion of subjects maintaining PASI75 response at Week 52 among subjects achieving PASI75 response at Week 16.
-Proportion of subjects maintaining PASI90 response at Week 52 among subjects achieving PASI90 response at Week 16.

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

Secondary ID(s)

A3921078

Source(s) of Monetary Support

Pfizer Inc