| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| A chronic, recurrent skin condition of variable severity. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
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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 |
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. |
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| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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) results must be obtained prior to Visit 1 (Baseline/Day 1). If the current incidence rates of multi-drug resistant TB infection in the locale are unavailable, an adequate treatment regimen should be defined as the regimen recommended by the health ministry or expert panel in the locale;
d. A subject who is currently being treated for active TB infection is to be excluded;
e. 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 Pfizer Medical Monitor (or designee). If the current incidence rates of multi-drug resistant TB infection in the locale are unavailable, an adequate treatment regimen should be defined as the regimen recommended by the health ministry or expert panel in the locale.
For inclusion condition 11 please refer to the protocol. |
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| E.4 | Principal 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 infection requiring oral or topical antimicrobial therapy within 2 weeks prior to Visit 1 (Baseline/Day 1).
12. Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to Visit 1 (Baseline/Day 1), or expects to be vaccinated with these vaccines during treatment or during the 6 weeks following the last dose of study drug.
13. Have had 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) or have received rituximab or other selective B-lymphocyte depleting agents (including experimental agents).
14. Have previously participated in any study of oral or topical tofacitinib (tofacitinib, CP-690,550, formerly known as tasocitinib), unless confirmed to have been randomized to and treated with placebo or placebo topical formulation (vehicle) only.
15. Have a history of alcohol or substance abuse, unless in full remission for greater than 6 months prior to Visit 1 (Baseline/Day 1).
16. A Screening 12-lead ECG that demonstrates clinically significant abnormalities requiring urgent treatment (eg, acute myocardial infarction, serious tachy- or bradyarrhythmias) or that are indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads).
For exclusion conditions 17 - 24 please refer to the protocol. |
|
| E.5 End points |
| E.5.1 | 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. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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). |
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| E.5.2.1 | 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.
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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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| 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 |
| Patient reported outcomes |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 6 |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| 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 |
| Denmark |
| Germany |
| Poland |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| End of Trial in all participating countries is defined as Last Subject Last Visit which is the last follow up visit for the last subject. |
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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