| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate To Severe Chronic Plaque Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| 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 |
| To evaluate the long term safety and tolerability of treatment with tofacitinib (10 mg BID or variable dose 5 and 10 mg BID) in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the durability of efficacy of tofacitinib (10 mg BID or variable 5 and10 mg BID) in adult 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 treatment with tofacitinib (10 mg BID or variable 5 and 10 mg BID) at various time points in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria that Apply to All subjects
1.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study
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 consent
4.Sexually active women of childbearing potential are required to use highly effective method of contraception during the study and for at least 28 days after treatment is discontinued.
5.If receiving non-prohibited 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 prior to first dose of study drug. Subject must be willing to stay on a stable regimen
6.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 to confirm period of discontinuation required. b. Ustekinumab (Stelara)
-Must be discontinued for at least 8 weeks prior to first dose of study drug
a. Adalimumab (Humira®) b. Infliximab (Remicade®) c. Alefacept (Amevive®)
-Must be discontinued for at least 4 weeks prior to first dose of study drug;
a. Etanercept (Enbrel®) not including potential treatment for subjects entering from qualifying protocol A3921080; Note: For subjects who participated in protocol A3921080, discontinuation from study drug treatment in protocol A3921080, for at least one week from Visit 5/Week 12 is required as washout criteria prior to entry into protocol A3921061. b. Systemic treatments other than biologics that could affect psoriasis, eg, oral or injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine,hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold. c. Psoralens + UVA phototherapy (PUVA)
-Must be discontinued for at least 2 weeks prior to first dose of study drug:
a. Topical treatments that could affect psoriasis, eg, corticosteroids, tars,keratolytics, anthralin, vitamin D analogs, and retinoids; Exceptions – the following topical treatments are allowed: non-medicated emollients for use over the whole body; low or least potent (Class 6or7) topical corticosteroids for the palms, soles, face, and intertriginous areas and scalp only; tar and salicylic acid preparations for the scalp only, and shampoos free of corticosteroids for the scalp only. b. UVB (narrowband or broadband) phototherapy
7.Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other ultraviolet light sources during the study. Note: Per exclusion criterion, prior treatment with efalizumab (Raptiva®) is exclusionary.
Inclusion Criteria that Apply only to Subjects who participated in Study A3921047
1.Have previously completed study A3921047 or were withdrawn/discontinued from that study, with the exception that subjects that were withdrawn/discontinued due to a tofacitinib related serious adverse event are not eligible for this study.
Inclusion Criteria that Apply only to (i) Subjects who Participated in Study A3921047 and (ii) Subjects who do not Enroll into This Study within a 2-week Window of the End of Study Visit of a Qualifying Phase 3 Study
1.Subject must have evidence of plaque-type psoriasis (psoriasis vulgaris) and be considered by dermatologist investigator to be a candidate for systemic therapy or phototherapy of psoriasis at screening
2.No evidence of active, 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 indeterminate upon retest, a Mantoux Purified Protein Derivative (PPD) skin or within the 3 months prior to Screening.
-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
For full criteria see section 4.1.3 of the protocol
Inclusion Criteria that apply only to Subjects who Enroll from a Qualifying Phase 3 Study at any Time Point
1.Have previously completed participation in a randomized qualifying study of CP-690,550 for the treatment of plaque psoriasis or;
-Were withdrawn from a randomized qualifying study for worsening of psoriasis or lack of efficacy after compliant participation of 12 weeks or greater
For full criteria see section 4.1.3 of the protocol |
|
| E.4 | Principal exclusion criteria |
Exclusion Criteria that Apply to All Subjects
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 the screening or baseline visit that would interfere with 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, intramuscular, intravenous, intraarticular) corticosteroids for any condition.
7.Women who are pregnant or lactating, or planning pregnancy while enrolled in the study.
8.Have current or recent history of severe, progressive, or uncontrolled renal, hepatic,hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
9.Have a history of any lymphoproliferative disorder (such as Epstein Barr Virus [EBV]-related lymphoproliferative disorder, as reported in some subjects on other
immunosuppressive drugs), history of lymphoma, leukemia, or signs and symptoms
suggestive of current lymphatic disease
10.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
11.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
12.Have a history of infection requiring antimicrobial therapy within 2 weeks prior to
first dose of study drug
13.Have been either vaccinated with live or attenuated 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 discontinuation of study drug
14.Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies.Subjects who have 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 CD 19/20+ counts by FACS analysis
15.Have previously been treated with efalizumab (Raptiva®)
16.Have any condition possibly affecting oral drug absorption, eg, gastrectomy,
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgerysuch as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary
17.Have a history of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug
18.Have a known immunodeficiency disorder or first-degree relative with a hereditary
immunodeficiency
19.Have any malignancies or have a history of malignancies with the exception of
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
20.Have undergone significant trauma or major surgery within 1 month prior to Screening
21. Known to be infected with human immunodeficiency virus (HIV), hepatitis B (see protocol appendix 8) or hepatitis C viruses. For additional Japan specific requirements see Appendix 6.
For Exclusion Criteria numbers 22 - 26, please see section 4.2.1 of the protocol.
For Exclusion Criteria that Apply only to (i) Subjects who Participated in Study A3921047 and (ii) Subjects who do not Enroll into This Study within a 2-week Window of the End of Study Visit of a Qualifying Phase 3 Study or study A3921147 see section 4.2.2 of the protocol
For Exclusion Criteria that Apply only to Subjects who Enroll from a Qualifying Phase 3 Study within a 2-week Window of the End of Study Visit or study A3921147 see section 4.2.3 of the protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
This protocol uses independent endpoint adjudication committees to
determine whether certain investigator-reported events meet the definition of disease-related efficacy endpoints, using pre-defined
endpoint criteria.
- Incidence and severity of adverse events during treatment.
- Incidence of clinical laboratory abnormalities and change from baseline (in this
and/or prior study) in clinical laboratory values during treatment.
- Incidence of investigator-reported clinically significant changes in physical
examination from baseline (in this and/or prior study) during treatment.
- Incidence of vital sign (blood pressure and heart rate) abnormalities and change from
baseline (in this and/or prior study) in vital sign measures during treatment.
- Incidence of electrocardiogram (ECG) abnormalities and change from baseline (in
this and/or prior study) in ECG measurements during treatment using data obtained until the implementation of Protocol
Amendment 17.
- Summary of adjudicated cardiovascular endpoints.
- Summary of malignancies confirmed by central laboratory pathologist over-read of
biopsies. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Baseline/Day 1, Months 3, 6, 9, and 12 and thereafter every 3 months. Open-Label ~5 years |
|
| E.5.2 | Secondary end point(s) |
Physician’s Global Assessment (PGA) response ie, the proportion of subjects achieving a PGA of “clear” or “almost clear” at various time points.
- Psoriasis Area and Severity Index 75 (PASI75) response ie, the proportion of subjects
achieving at least a 75% reduction in PASI relative to Baseline/Day 1 (in this and/or
prior study) at various time points. The actual and change from Baseline/Day 1 (in this and/or prior study) in PASI and PASI component scores at various time points. The proportion of subjects achieving at least a 50% and 90% reduction in PASI relative to Baseline/Day 1 (in this and/or prior study) (ie, PASI50 and PASI90,
respectively) at various time points. Proportion of subjects with a PASI score ≥125% of the Baseline/Day 1 PASI score (in this and/or prior study) at any time point. The actual and change from Baseline/Day 1 (in this and/or prior study) in the Itch Severity Item (ISI) score at various time points. The actual and change from Baseline/Day 1 (in this and/or prior study) on the Dermatology Life Quality Index (DLQI) score at various time points. Other patient reported outcome (PRO) measures to be assessed at various time points, including: Short Form-36 Health Survey (Version 2, Acute) (SF-36);
-Patient Global Assessment (PtGA);
-Euro-Qol 5 Dimensions (EQ-5D);
- Psoriasis Healthcare Resource Utilization Questionnaire (Ps-HCRU).After implementation of Protocol Amendment 17, certain PROs (eg, SF-
36, EG-5D, Ps-HCRU) will not be assessed. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Assessment of secondary endpoints are defined within the protocol |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability - effects on patient reported outcome |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 222 |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Bosnia and Herzegovina |
| Brazil |
| Bulgaria |
| Canada |
| Chile |
| Colombia |
| Croatia |
| Czech Republic |
| Denmark |
| Finland |
| France |
| Germany |
| Greece |
| Hong Kong |
| Hungary |
| Israel |
| Italy |
| Korea, Republic of |
| Mexico |
| Netherlands |
| Poland |
| Portugal |
| Serbia |
| Singapore |
| Slovakia |
| Spain |
| Sweden |
| Switzerland |
| Taiwan |
| Turkey |
| Ukraine |
| United Arab Emirates |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| As per protocol section 13.1. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 11 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
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