E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis |
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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. |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
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 |
To evaluate and compare the maintenance of effect of two doses of PF-04965842 (200 mg and 100 mg once daily [QD]) and placebo in subjects aged 12 and above with moderate to severe atopic dermatitis who respond to an initial open-label run-in treatment of 200 mg PF-04965842 QD. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate and compare the effect of PF-04965842 on additional efficacy endpoints and patient-reported outcomes over time in subjects aged 12 years and older with moderate to severe atopic dermatitis.
• To assess the efficacy of open-label rescue treatment consisting of 200 mg PF-04965842 in combination with topical therapy per standard of care in cases of flare (per protocol definition).
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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 his/her legally acceptable representative/parent(s) or legal guardian if a minor, 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 legal age of majority (legal adulthood) in the subject’s country will only be enrolled in this study if instructed by the sponsor and approved by the country’s regulatory/health authority. If these approvals have not been granted, only subjects ≥ the legal age of majority (legal adulthood) in the subject’s country will be enrolled.
3. Meet all the following atopic dermatitis criteria:
• Clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for at least 1 year prior to Day 1 and has confirmed atopic dermatitis at the screening and baseline visits according to Hanifin and Rajka criteria of AD .
• Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with medicated topical therapy for AD for at least 4 weeks, or who have required systemic therapies for control of their disease.
NOTE: Medicated topical therapy is defined as a topical product that contains an active pharmaceutical ingredient indicated for the treatment of AD (irrespective of whether it is an over-the -counter [OTC] or prescription only product).
• Moderate to severe AD (affected BSA ≥10%, IGA ≥3, EASI ≥16 and pruritus NRS severity ≥4 on the day of the baseline visit).
4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
5. Female subjects who are of child-bearing potential (which includes adolescents 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 treatment with investigational product;
b. Female subjects of childbearing potential 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.
NOTE: Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with 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:
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure; or
• 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.
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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. Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria:
• 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);
• 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;
• Any lifetime history of serious or recurrent suicidal behavior;
• Suicidal behaviors questionnaire – revised (SBQ-R) total score ≥8;
• Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) total score ≥15;
• The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria;
• In the opinion of the investigator or Pfizer (or designee) exclusion is required.
3. A current or past medical history of conditions associated with thrombocytopenia, coagulopathy or platelet dysfunction.
4. Receiving anti-coagulants or medications known to cause thrombocytopenia (unless considered safe to stop and washout for the duration of the study).
5. Currently have active forms of other inflammatory skin diseases, i.e., not AD or have evidence of skin conditions (e.g., psoriasis, seborrheic dermatitis, Lupus) at the time of Day 1 that would interfere with evaluation of atopic dermatitis or response to treatment.
6. Vaccinated or exposed to a live or attenuated vaccine within the 6 weeks prior to the first dose of investigational product, or is expected to be vaccinated or to have household exposure to these vaccines during treatment or during the 6 weeks following discontinuation of investigational product.
7. Adolescent subjects 12 to <18 years old without documented evidence of having received at least one dose of the varicella vaccine in countries where the vaccine is approved and standard of care or those who do not have evidence of prior exposure to varicella zoster virus (VZV) based on serological testing (i.e., varicella zoster virus immunoglobulin G antibody [VZV IgG Ab]) at screening.
8. Subjects who have received prior treatment with any JAK inhibitors.
Refer to protocol for additional criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Loss of response requiring rescue treatment will be evaluated and compared among groups during the blinded treatment period. Loss of response is denoted as flare and is defined as a loss of at least 50% of the Eczema Area and Severity Index (EASI) response at Week 12 and an Investigator’s Global Assessment (IGA) score of 2 or higher.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through out the blinded treatment period |
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E.5.2 | Secondary end point(s) |
Key Secondary Endpoint
1. Loss of response based on an IGA score of 2 or higher.
Clinical Efficacy Assessments
Treatment:
1. Response based on the IGA (score of 0 or 1 and a reduction of ≥2 points) at all scheduled time points.
2. Response based on EASI total score (EASI 50, EASI 75, EASI 90, and EASI 100) at all scheduled time points.
3. Response based on achieving ≥4 point improvement in the severity of pruritus Numerical Rating Scale (NRS) from baseline at all scheduled time points.
4. Percentage change from baseline in percent Body Surface Area (BSA) at all scheduled time points.
5. Percentage change from baseline in SCORing Atopic Dermatitis (SCORAD) subjective assessments of itch and sleep loss at all scheduled time points.
6. Response based on achieving a ≥50% and ≥75% improvement in SCORAD (SCORAD-50, SCORAD-75) from baseline at all scheduled time points.
Clinical Efficacy Assessments in Subjects Requiring Rescue Treatment:
1. Response based on the IGA at the end of rescue therapy.
2. Response based on the EASI total score at the end of rescue therapy.
3. Response based on achieving ≥4 point improvement in the severity of pruritus Numerical Rating Scale (NRS) at the end of rescue therapy relative to the start of rescue therapy baseline value.
4. Percent change in percent Body Surface Area (BSA) at the end of rescue therapy relative to start of rescue therapy baseline value.
5. Percent change in SCORAD subjective assessments of itch and sleep loss at the end of rescue therapy relative to start of rescue therapy baseline value.
6. Response based on achieving a ≥50% and ≥75% improvement in SCORAD (SCORAD-50, SCORAD-75) at the end of rescue therapy relative to start of rescue therapy baseline value.
Patient-Reported Outcomes in All Subjects:
1. Response based on achieving PtGA score of clear (0) or almost clear (1); and a reduction from baseline of ≥2 points at all scheduled time points (among subjects with a score ≥2 at baseline).
2. Change from baseline in Dermatology Life Quality Index (DLQI) or Children’s DLQI (CDLQI) at all scheduled time points.
3. Change from baseline in Hospital Anxiety Depression Scale (HADS) at all scheduled time points.
4. Change from baseline in Patient Oriented Eczema Measure (POEM) at all scheduled time points.
5. Change from baseline in the Pruritus and Symptoms Assessment in Atopic Dermatitis (PSAAD) at all scheduled time points. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At all scheduled timepoints; or if rescue therapy is required at the end of the rescue therapy |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 141 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Czechia |
Germany |
Israel |
Italy |
Latvia |
Mexico |
Netherlands |
Poland |
Russian Federation |
Serbia |
Slovakia |
Spain |
Taiwan |
United States |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |