| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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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 compare the efficacy of crisaborole ointment, 2% applied BID versus vehicle in pediatric and adult subjects, aged 2 years and older, with mild to moderate AD.
To evaluate the safety and local tolerability of crisaborole ointment 2% applied BID versus vehicle in pediatric and adult subjects (ages 2 years and older) with mild to moderate AD.
To evaluate the safety and local tolerability of hydrocortisone butyrate cream 0.1% and pimecrolimus cream 1% applied BID in pediatric and adult subjects (ages 2 years and older) with mild to moderate AD. |
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| E.2.2 | Secondary objectives of the trial |
To evaluate the effect of crisaborole ointment, 2% applied BID versus vehicle on additional efficacy endpoints over time in pediatric and adult subjects (ages 2 years and older) with mild to moderate AD .
To evaluate the efficacy of crisaborole ointment, 2% BID versus hydrocortisone butyrate cream 0.1% and pimecrolimus cream 1% applied BID in pediatric and adult subjects (ages 2 years and older) with mild to moderate AD.
To evaluate the effect of crisaborole ointment, 2% applied BID versus vehicle, hydrocortisone butyrate cream 0.1% applied BID on patient/observer reported outcomes over time in pediatric and adult subjects (ages 2 years and older) with mild to moderate AD. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optical Coherence Tomography Sub-Study – A Study of Optical Coherence Tomography and Biomarkers in Subjects ages 2 to <18 years old, with Mild to Moderate Atopic Dermatitis, treated with Crisaborole Ointment, 2% or Crisaborole Vehicle Ointment or Hydrocortisone Butyrate 0.1% Cream applied BID.
The primary objective of this sub-study is to evaluate the differences in atrophic changes in epidermal thickness by structural OCT after treatment with crisaborole ointment, 2% or crisaborole vehicle ointment, or hydrocortisone butyrate 0.1% cream applied BID for 28 days.
The secondary objectives of this sub-study are to evaluate the differences in atrophic change in epidermal thickness, skin biomarkers of AD, and TEWL during the course of treatment and following treatment with crisaborole ointment, 2% or crisaborole vehicle ointment, or hydrocortisone butyrate 0.1% cream applied BID for 28 days.
This sub-study is expected to provide OCT, TEWL, and skin biomarker evidence of the effects of crisaborole ointment and vehicle ointment compared to TCS.
This sub-study is planned to be conducted at selected sites in Germany, United Kingdom and the United States only. |
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| E.3 | Principal inclusion criteria |
1. Is male or female 2 years and older at the Screening visit/time of informed consent/assent.
2. Has a clinical diagnosis of AD according to the criteria of Hanifin and Rajka (See Appendix 2).
3. Has AD involvement of ≥ 5% Treatable %BSA (excluding the scalp) at Baseline/Day 1.
4. Has an ISGA score of Mild (2) or Moderate (3) (excluding the scalp) at Baseline/Day 1.
5. Female subjects of childbearing potential who have a negative urine pregnancy test at the screening visit and negative urine pregnancy test at the baseline visit prior to randomization. A female is of childbearing potential if, in the opinion of the investigator, she is biologically capable of having children (includes any female who has experienced menarche and does not meet the criteria for females not of childbearing potential).
6. Female subjects of non-childbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
7. Evidence of a personally signed and dated informed consent/assent document indicating that the subject [or parent(s)/legal guardian] has been informed of all pertinent aspects of the study.
8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Additional Inclusion Criteria for Cohort 1 and Cohort 2 and can be found in the Protocol. |
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| E.4 | Principal exclusion criteria |
1. Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non-AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome) or clinically significant physical examination finding that in the PI’s or designee’s opinion may interfere with study objectives (eg, expose subject to unacceptable risk by study participation, confound evaluation of treatment response or AEs, or interfere with subject’s ability to complete the study).
2. Has unstable AD or a history of requirement for high/strong potency or very high/very strong potency topical corticosteroids to manage AD signs and symptoms (See Appendix 3).
3. Has a significant active systemic or localized infection, including known actively infected AD.
4. History of or active suicidal ideation or behavior, or chronic psychiatric 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 including the following:
For subjects 7-11 years of age, suicidal ideation associated with actual intent and a method or plan in the past 6 months: “Yes” answers on items 4 or 5 of the Children’s Columbia suicide severity rating scale (C-SSRS) or a previous history of suicidal behaviors in their lifetime: “Yes” answer to any of the suicidal behavior items of the Children’s C-SSRS.
For subjects >=12 years of age, suicidal ideation associated with actual intent and a method or plan in the past year: “Yes” answers on items 4 or 5 of the C-SSRS or a 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.
5. Pregnant female subjects; breastfeeding female subjects; and female of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
6. Has received any of the prohibited medications/therapies that may alter the course of AD without the required minimum washout period (see Section 5.8.1) or anticipated concomitant use of any of the prohibited medications/therapy (see Section 5.8.2).
7. Has any planned surgical or medical procedure that would overlap with study participation, from Screening through the end of study.
8. Has a history of cancer within 5 years or has undergone treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only).
9. Has a history of angioedema or anaphylaxis to topical products or known sensitivity to any of the components of the investigational products.
10. Has a known lack of efficacy to crisaborole.
11. Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
12. Other acute or chronic medical 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.
13. 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.
Aditional exclusion criteria for Cohort 1 and Cohort 2 and can be found in the Protocol. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Percent change from Baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.
AEs, SAEs, local tolerability, discontinuations and clinically significant changes in vital signs and clinical laboratory parameters. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoint at Day 29.
Safety endpoints along the study. |
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| E.5.2 | Secondary end point(s) |
Efficacy endpoints:
-Percent change from Baseline in EASI total score by scheduled time points except Day 29.
-Achievement of success in the Investigator’s Static Global Assessment (ISGA) (defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2-grade improvement from Baseline) by scheduled time points.
-Achievement of ISGA score of clear (0) or almost clear (1) by scheduled time points.
-Achievement of EASI75 (>=75% improvement from Baseline) by scheduled time points.
-Time to EASI75.
-Change from Baseline in % BSA by scheduled time points. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| 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 | 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| pimecrolimus and hydrocortisone butyrate cream |
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| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 |
| Belgium |
| Germany |
| Italy |
| Netherlands |
| Poland |
| Sweden |
| Switzerland |
| United Kingdom |
| 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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| End of trial in all participating countries is defined as last subject last visit (LSLV). |
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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 | 26 |
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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