E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Moderate to severe atopic dermatitis | |
E.1.1.1 | Medical condition in easily understood language | Atopic dermatitis is also known as atopic eczema. It is a type of inflammation of the skin that results in itchy, red, swollen, and cracked skin. | |
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 | 10003639 | E.1.2 | Term | Atopic dermatitis | 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 | To estimate the long-term safety of 100 mg and 200 mg once daily (QD) of PF-04965842 with or without topical treatments in adult and adolescent subjects who previously participated in PF-04965842 atopic dermatitis (AD) Phase 3 trials. | |
E.2.2 | Secondary objectives of the trial | To estimate the long-term efficacy of PF-04965842. | |
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 or their parent(s)/legal guardian, if applicable, have been informed of all pertinent aspects of the study. 2. Male or female subjects of 12 years of age or older, at the time of informed consent and body weight ≥ 40 kg. Adolescent subjects below the age of 18 years old (or country-specific age of majority) will only be enrolled in this study if instructed by the sponsor and approved by the country or regulatory/health authority. If these approvals have not been granted, only subjects aged 18 years (or country-specific age of majority) and older will be enrolled. 3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 4. Must have completed the full treatment period of a qualifying Phase 3 study OR must have completed the full rescue treatment period of a qualifying Phase 3 study (if applicable). OR must have completed the full open-label run-in period in B7451014 and did not meet the protocol-specified response criteria at week 12. 5. Female subjects who are of childbearing potential (which includes all female subjects aged 12 years and older, regardless of whether they have experienced menarche) must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply: a. Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to allocation to treatment. b. Female subjects of childbearing potential must agree to use a highly effective method of contraception (as per Section 4.4.1) for the duration of the active treatment period and for at least 28 days after the last dose of investigational product. For Czech Republic only, 5 b. is revised and 5 c. is added to require: Female subjects of childbearing potential ≥15 years of age who are at risk of pregnancy must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of investigational product; c. Female subjects less than 15 years of age must not be sexually active, and abstinence per the below definition should be confirmed prior to enrollment. NOTE: Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with the study treatments) may obviate the need for contraception ONLY if this is the preferred and usual lifestyle of the subject. 6. Female subjects of non-childbearing potential must meet at least 1 of the following criteria: a. Have undergone a documented hysterectomy and/or bilateral oophorectomy; b. Have medically confirmed ovarian failure; or c. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential. 7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during the study. 8. Must agree to avoid use of prohibited medications throughout the duration of the study, as detailed in Appendix 2 and Appendix 3. | |
E.4 | Principal exclusion criteria | 1. 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 subject inappropriate for entry into this study. 2. Currently have active forms of other inflammatory skin diseases, ie, not AD. 3. Have evidence of skin conditions (eg, psoriasis, seborrheic dermatitis, Lupus) at the time of Day -1 that would interfere with evaluation of atopic dermatitis or response to treatment. 4. Discontinued from treatment (or rescue treatment period/open-label run-in period, if applicable) early in a qualifying Phase 3 study OR triggered discontinuation criteria at any point during the qualifying Phase 3 study OR meets exclusion criteria from qualifying Phase 3 studies as detailed in Appendix 10 of the protocol. 5. Ongoing adverse event in the qualifying Phase 3 study which in the opinion of the investigator, or sponsor, is an ongoing safety concern OR the subject is currently triggering safety monitoring criteria in the qualifying Phase 3 study. 6. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study. | |
E.5 End points |
E.5.1 | Primary end point(s) | Primary (Safety) Endpoints • The incidence of treatment emergent adverse events. • The incidence of serious adverse events and adverse events leading to discontinuation. • The incidence of clinical abnormalities and change from baseline in clinical laboratory values, electrocardiogram (ECG) measurements, and vital signs. | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | |
E.5.2 | Secondary end point(s) | Baseline, for efficacy endpoints, is defined as pre-dose Day 1 in the qualifying Phase 3 study. • Response based on achieving the Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1) (on a 5-point scale) and a reduction from baseline of ≥ 2 points at all scheduled time points. • Response based on achieving ≥ 50%, ≥ 75% and ≥ 90% improvement from baseline in the Eczema Area and Severity Index (EASI) total score (EASI50, EASI75, and EASI90) at all scheduled time points. • Response based on achieving an improvement ≥ 4 points from baseline in the severity of pruritus NRS at all scheduled time points. • Change from baseline in the frequency of itching due to Atopic Dermatitis • Change from baseline of Patient Global Assessment (PtGA) at all scheduled time points. • Change from baseline in the percentage Body Surface Area (BSA) affected at all scheduled time points. • Change from baseline in Dermatology Life Quality Index (DLQI) or Children’s DLQI (CDLQI) at all scheduled time points. • Change from baseline in Patient Oriented Eczema Measure (POEM) at all scheduled time points. • Change from baseline in Hospital Anxiety and Depression Scale (HADS) at all scheduled time points. • Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) or EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) at all scheduled time points. • Steroid-free days. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | At all scheduled timepoints | |
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 | No |
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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 | Belgium | Brazil | Bulgaria | Canada | Chile | China | Colombia | Czech Republic | France | Germany | Hungary | Israel | Italy | Japan | Korea, Republic of | Latvia | Mexico | Netherlands | Peru | Poland | Romania | Russian Federation | Serbia | Slovakia | Spain | Sweden | Switzerland | Taiwan | United Kingdom | 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 a Member State of the EU is defined as the time at which it is deemed that a sufficient number of subjects have been recruited and completed the study as stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |