| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate to severe Plaque Psoriasis |
|
| E.1.1.1 | Medical condition in easily understood language |
| The most common variant of psoriasis or plaque psoriasis, is a chronic inflammatory autoimmune skin disease characterized by red, scaly, raised plaques. |
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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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| 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 |
The purpose of this multicenter, placebo controlled double blind study is to provide additional efficacy, safety, tolerability and pharmacokinetics data regarding PF-06826647 in the oral treatment of moderate to severe plaque psoriasis. It is intended to enable dose selection for the future development of PF-06826647.
For the Investigational Treatment Period, the primary objective is to compare the efficacy of multiple dose levels of PF-06826647 versus placebo on the proportion of participants with moderate to severe plaque psoriasis achieving Psoriasis Area Severity Index (PASI) 90.
For the Extension Treatment Period, the primary objective is to assess the safety and tolerability of PF-06826647 in participants with moderate to severe plaque psoriasis. |
|
| E.2.2 | Secondary objectives of the trial |
For the Investigational Treatment Period; to compare the efficacy of multiple dose levels of PF-06826647 versus placebo on the proportion of participants with moderate to severe plaque psoriasis achieving PASI 75.
To compare the efficacy of multiple dose levels of PF-06826647 versus placebo on Physician Global Assessment (PGA) score in participants with moderate to severe plaque psoriasis.
To compare the efficacy of multiple dose levels of PF-06826647 versus placebo on the proportion of participants with moderate to severe plaque psoriasis achieving PASI 50 and PASI 100.
To compare the efficacy of multiple dose levels of PF-06826647 versus placebo on PGA and PASI scores in participants with moderate to severe plaque psoriasis.
Please refer to protocol section 3.1 for a complete list of secondary objectives for the Investigational Treatment Period and Extension Treatment Period. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 75 years, inclusive, at Screening.
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Participants with a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 6 months prior to Baseline/Day 1 (prior to first dose of study drug).
4. Have a PASI score of 12 or greater AND a Physician Global Assessment score of 3 (“moderate”) or 4 (“severe”) at Baseline/Day 1 (prior to first dose of study drug).
5. Have plaque type psoriasis covering at least 10% of total body surface area (BSA) at Baseline/Day 1 (prior to first dose of study drug).
6. ody weight must be >40 kg.
7. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
8. Must discontinue systemic, topical and/or phototherapy therapies (eg, ultraviolet B (UVB) or photochemotherapy (PUVA)) for the treatment of psoriasis per timing criteria described in Section 5.2. |
|
| E.4 | Principal exclusion criteria |
1. Currently have non plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis, except for nail psoriasis which is allowed.
2. Evidence of other skin conditions (eg, eczema) at the time of screening or baseline visit that would interfere with the evaluation of psoriasis.
3. 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 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 (whichever is longer) prior to first dose of study drug.
5. Any psychiatric condition including recent (within the past year) or active suicidal ideation or behavior that meets any of the following criteria:
a. Suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale (C SSRS) (10.9).
b. Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C SSRS.
c. In the opinion of the investigator or Sponsor (or designee) exclusion is required.
6. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary.
7. Have current or recent (within the past year) history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
8. 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.
9. History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
10. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 3 months prior to first dose of study drug or a history of infection requiring oral antimicrobial therapy within 2 weeks prior to first dose of study drug.
11. Infected with Mycobacterium tuberculosis (TB) (see Section 8.2.1.1).
12. Have known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
13. History of recurrent (>2) venous thrombosis or any arterial thromboembolism or known blood clotting disorders.
14. History of acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and any history of cerebrovascular disease within 24 weeks before screening.
15. Have any malignancies or 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.
16. Have undergone significant trauma or major surgery within 1 month prior to Screening or plan to undergo surgery during treatment period.
17. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. For any reason in the opinion of the investigator or sponsor, the participant is inappropriate for entry into this study.
18. 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.
19. Are taking or require oral or injectable (eg, intraarticular, intramuscular or intravenous) corticosteroids for any condition.
20. 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 8 weeks following the last dose of study drug. (For further information regarding avoidance of household contacts who may be vaccinated see Section 5.3.2).
Please refer to protocol section 5.2 for a full list of exclusion criteria with respect to diagnostic assessments and other exclusions. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
For the Investigational Treatment Period; Proportion of participants achieving PASI 90 (90% or greater improvement from Baseline) at Week 16.
For the Extension Treatment Period the primary endpoints are:
• Incidence and severity of adverse events, serious adverse events and withdrawals due to adverse events.
• Change from baseline in clinical laboratory values (chemistry, hematology & lipids).
• Incidence of clinically significant changes in ECG (heart rate, QT, QTc, PR and QRS intervals).
• Change from baseline in vital signs (blood pressure, pulse rate and temperature measurements).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
For the Investigational Treatment Period: Baseline and Week 16
For the Extension Treatment Period: Week 16 - Week 40 |
|
| E.5.2 | Secondary end point(s) |
For the Investigational Treatment Period the key secondary endpoint is:
• Proportion of participants achieving PASI 75 (75% or greater improvement from Baseline) at time points specified in the Schedule of Activities (SoA).
For the Investigational Treatment Period the secondary endpoints are:
• Proportion of participants with PGA score clear (0) or almost clear (1) and ≥ 2 points improvement from baseline at time points specified in the SoA.
• Proportion of participants with PGA score clear (0) or almost clear (1) at time points specified in the SoA.
• Proportion of participants achieving PASI 50 (50% or greater improvement from Baseline), PASI 100 (100% from Baseline) at time points specified in the SoA.
• Change from baseline and percent change from baseline in PASI scores at time points specified in the SoA.
• Absolute score and change from baseline in Peak Pruritus Numerical Rating Scale score at time points specified in the SoA.
• Incidence and severity of adverse events, serious adverse events and withdrawals due to adverse events.
• Change from baseline in clinical laboratory values (chemistry and hematology, lipids).
• Incidence of clinically significant changes in ECG (heart rate, QT, QTc, PR and QRS intervals).
• Change from baseline in vital signs (blood pressure, pulse rate and temperature measurements).
• Absolute score and change from baseline Psoriasis Symptom Inventory at time points specified in the SoA.
There are no identified secondary endpoints for the Extension Treatment Period. Please refer to section 3.1 of the clinical trial protocol for a list of exploratory endpoints for the Investigational Treatment Period and Extension Treatment Period. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Individual timepoints are included in each bullet point above with reference to the SoA, contained within section 1.3 of the clinical trial 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 |
|
| 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 | 5 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 7 |
| 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 |
| Japan |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 20 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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