Study to test efficacy, tolerability, safety and pharmacokinetics of Tofacitinib ointment in subjects with mild, moderate or severe chronic plaque psoriasis.

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2012-005645-20-DK
• Date of registration: 25/06/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, 10017
• Public title: Study to test efficacy, tolerability, safety and pharmacokinetics of Tofacitinib ointment in subjects with mild, moderate or severe chronic plaque psoriasis.
• Scientific title: A PHASE 2B, MULTI-SITE, RANDOMIZED, DOUBLE-BLIND, VEHICLE-CONTROLLED, PARALLEL-GROUP STUDY OF THE EFFICACY, SAFETY, LOCAL TOLERABILITY AND PHARMACOKINETICS OF 2 DOSE STRENGTHS AND 2 REGIMENS OF TOFACITINIB OINTMENT IN SUBJECTS WITH CHRONIC PLAQUE PSORIASIS
• Date of first enrolment: 25/06/2013
• Target sample size: 480
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005645-20
• 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: 6

Countries of recruitment

Canada, Denmark, Germany, Poland, 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 that the subject has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, study drug application to all treatment eligible plaques, 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 psoriasis (psoriasis vulgaris) for at least 6 months prior to Visit 1 (Baseline/Day 1).
5. Have a PGA-C score of 2 (mild), 3 (moderate) or 4 (severe) at Visit 1 (Baseline/Day 1).
6. At Visit 1 (Baseline/Day 1), have plaque psoriasis covering 2% to 20% of total body surface area (BSA) on the trunk and limbs (excluding palms, soles, and nails) with at least 1% BSA involvement on the trunk or limbs excluding palms, soles, elbows, knees and below the knee areas. Plaque psoriasis of the scalp, palms or soles, and nail psoriasis will not be included in the total BSA with psoriasis to determine eligibility.
7. Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children and is sexually active.
8. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths, sun lamps or other ultraviolet light sources during the study.
9. If receiving 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 Visit 1 (Baseline/Day 1). Subject must be willing to stay on a stable regimen.
10. No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by the following:
a. A negative QuantiFERON-TB Gold (QFT-G) In-Tube test or negative Mantoux/Purified Protein Derivative (PPD) tuberculin skin test performed at or within the 3 months prior to Screening. A positive QuantiFERON-TB Gold (QFT-G) In-Tube test or positive Mantoux/Purified Protein Derivative (PPD) tuberculin skin test is exclusionary. It is recommended that subjects with a history of Bacille Calmette Guérin (BCG) vaccination be tested with the QFT-G test since the Mantoux/PPD tuberculin skin test may be positive due to vaccination. See Section 7.4.5 for requirements for Mantoux/PPD tuberculin skin testing. A QFT-G or Mantoux/PPD tuberculin skin test is not required if the subject has previously received a documented adequate course of therapy for either latent or active TB infection or is currently receiving a documented adequate treatment for latent TB infection;
b. No history of either untreated or inadequately treated latent or active TB infection;
c. 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 Mantoux/PPD tuberculin skin test is needed, but a chest radiograph(s) (per local standard/guidelines) must be obtained if not performed within 3 months prior to a given Screening visit.
Documentation of adequate treatment for TB and negative chest radiograph(s)
Exclusion criteria:
1. Currently have non-plaque forms of psoriasis, (eg, erythrodermic, guttate, or pustularpsoriasis, keratoderma blennorrhagicum [Reiter’s syndrome]) with the exception of nail psoriasis which is allowed. Psoriasis of palms and soles is allowed only if considered to be part of the generalized plaque psoriasis. Subjects with other forms of palmo-plantar psoriasis (eg, palmo-plantar involvement as part of keratoderma blennorrhagicum, pustular psoriasis of the palms and soles, or pustular psoriasis of the digits) are to be excluded.
2. 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.
3. Have evidence of skin conditions (eg, eczema, fungal infection) at the time of Visit 1 (Baseline/Day 1) that would interfere with evaluation of psoriasis.
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 Visit 1 (Baseline/Day 1) and/or during the study.
5. The following laboratory values at the Wash-out or Screening visit:
a. Hemoglobin <10.0 g/dL or hematocrit <30%
b. White blood cell count <3.0 x 10 9 /L (<3000/mm3)
c. Absolute neutrophil count of <1.5 x 10 9 /L (<1500/mm3)
d. Absolute lymphocyte count of <0.5 x 10 9 /L (<500/mm3)
e. Platelet count <100 x 10 9 /L (<100,000/mm3)
f. Estimated Creatinine Clearance <40 mL/min based on the Cockcroft-Gault calculation (Appendix 1) or serum creatinine >1.5 times the upper limit of normal (ULN)
g. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 times the ULN
h. Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study.
6. Pregnant females, breastfeeding females, or females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception (per Section 4.4.5.1) for at least 28 days after last dose of investigational product.
7. Have current or recent history of clinically significant severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, psychiatric or neurological disease; or have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or interfere with the interpretation of study results; or in the opinion of the investigator or Pfizer (or designee), the subject is inappropriate for entry into this study, or unwilling/unable to comply with study procedures and life style guidelines.
8. 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 or lymphoid disease.
9. 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.
10. Have a history of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Visit 1 (Baseline/Day 1).
11. Have a history of i

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

Health Condition(s) or Problem(s) studied

Chronic Plaque Psoriasis
MedDRA version: 16.0 Level: LLT Classification code 10071117 Term: Plaque psoriasis System Organ Class: 100000004858

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

Intervention(s)

Product Name: tofacitinib
Product Code: CP-690,550-00
Pharmaceutical Form: Ointment
INN or Proposed INN: TOFACITINIB
CAS Number: 477600-75-2
Current Sponsor code: CP-690,550-00
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Ointment
Route of administration of the placebo: Cutaneous use

Product Name: tofacitinib
Product Code: CP-690,550-00
Pharmaceutical Form: Ointment
INN or Proposed INN: TOFACITINIB
CAS Number: 477600-75-2
Current Sponsor code: CP-690,550-00
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Ointment
Route of administration of the placebo: Cutaneous use

Primary Outcome(s)

Secondary Objective: Characterize effects on patient reported outcome (PRO) measures of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks of treatment in subjects with mild or moderate chronic plaque psoriasis.

-Determine the pharmacokinetics (PK) of tofacitinib when applied as an ointment (10 mg/g and 20 mg/g) QD or BID over 12 weeks in subjects with chronic plaque psoriasis.
-Characterize efficacy by baseline severity of psoriasis tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks of treatment in subjects with mild, moderate, or severe chronic plaque psoriasis.
-Characterize efficacy by body region of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks of treatment in subjects with mild or moderate chronic plaque psoriasis.
-Characterize local tolerability by body region of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks of treatment in subjects with mild or moderate chronic plaque psoriasis.

Main Objective: 1. To characterize the efficacy of tofacitinib ointment (10 mg/g and 20 mg/g) applied once daily (QD) or twice daily (BID) over 12 weeks in subjects with mild or moderate chronic plaque psoriasis compared to the corresponding placebo ointment (vehicle) (QD or BID).
2. To characterize safety of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks in subjects with mild or moderate chronic plaque psoriasis.
3. To characterize local tolerability of tofacitinib ointment (10 mg/g and 20 mg/g) applied QD or BID over 12 weeks in subjects with mild or moderate chronic plaque psoriasis.

Primary end point(s): The primary efficacy endpoints will be analyzed for subjects with mild or moderate psoriasis as defined by the baseline Calculated Physician's Global Assessment (PGA-C) score and include the proportion of subjects achieving a PGA-C response of “clear” (0) or “almost clear” (1) and =2 grade/point improvement from baseline at Week 8, and the proportion of subjects achieving a PGA-C response of “clear” (0) or “almost clear” (1) and 2 = grade/point improvement from baseline at Week 12.

Timepoint(s) of evaluation of this end point: Week 8 and Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy Endpoint: Week 8 and Week 12.
Safety and local tolerability endpoint: All 12 weeks of the treatment period.
PK endpoints: Week 2, Week 4, Week 8 and Week 12.

Secondary end point(s): The secondary efficacy endpoints (measured at Week 8 and at Week 12 separately) include the proportion of subjects achieving a PGA-C response of “clear” (0) or “almost clear” (1); the proportion of subjects achieving a Gestalt Physician's Global Assessment (PGA-G) response of “clear” (0) or “almost clear” (1) and =2 grade/point improvement from baseline; the percent change from baseline in Psoriasis Area and Severity Index (PASI); Psoriasis Area and Severity Index 75 (PASI75) response, ie, the proportion of subjects achieving at least a 75% reduction in PASI relative to baseline; and the percent change from baseline in Body Surface Area (BSA) affected with psoriasis.

Safety Endpoints: Safety endpoints include incidence of treatment-emergent adverse events (AE) and specific clinical laboratory abnormalities.

Local Tolerability Endpoints: These include percent of subjects discontinued due to application site adverse events, and incidence of local tolerability AEs.

PK Endpoints: PK analyses include tofacitinib PK concentration for pre-dose samples (all subjects) and post-dose samples (subjects of selected sites).

Secondary ID(s)

A3921082

Source(s) of Monetary Support

Pfizer Inc