E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild-to-Moderate Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Mild-to-Moderate Atopic Dermatitis |
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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 | 10003640 |
E.1.2 | Term | Atopic dermatitis and related conditions |
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 |
Efficacy: To evaluate the long-term efficacy of crisaborole ointment, 2%, QD for maintenance therapy and flare reduction in pediatric and adult participants ≥2 years of age with mild-to-moderate AD who responded to crisaborole ointment, 2%, BID treatment.
Safety: To evaluate the safety and local tolerability of crisaborole ointment, 2%, QD for maintenance therapy and flare reduction in pediatric and adult participants ≥2 years of age with mild-to-moderate AD |
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E.2.2 | Secondary objectives of the trial |
- To evaluate other long-term efficacy
parameters for maintenance therapy
and flare reduction of crisaborole
ointment, 2%, QD in pediatric and
adult participants ≥2 years of age with
mild-to-moderate AD who responded
to crisaborole ointment, 2%, BID
treatment
- To evaluate the long-term efficacy of
crisaborole ointment, 2%, QD for
maintenance therapy and flare
reduction in participants ≥2 years of
age with mild-to-moderate AD
- To evaluate the long-term health
impact of crisaborole ointment, 2%,
QD for maintenance therapy and flare
reduction in participants ≥2 years of
age 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 |
Accelerometry Sub-study
Objective: The objective of the exploratory sub-study is to quantitatively evaluate night time
scratch and sleep quantity in response to crisaborole treatment.
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E.3 | Principal inclusion criteria |
Age
1. Participant must be 2 years of age or older at the time of signing the informed consent/assent.
Type of Participant and Disease Characteristics
2. Participant who meets the following AD criteria:
a. Confirmed clinical diagnosis of AD according to the criteria of Hanifin and Rajka (see Appendix 6).
b. AD treatment naïve, prior non-responder to emollient use, or has been previously treated with TCSs or TCIs.
c. AD involvement of ≥5% Treatable % BSA (excluding the scalp) (see Table 4) at entry into the run-in period.
d. ISGA score of Mild (2) or Moderate (3) at entry into the open-label run-in period.
Sex
3. Male or Female
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a. Male participants:
No contraception methods are required for male participants in this study.
b. Female participants:
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using an acceptable contraceptive method as described in Appendix 4 during the intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
- A WOCBP must have a negative highly sensitive (Appendix 2) pregnancy test (urine or serum as required by local regulations) within 7 days before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2.
* The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
Informed Consent
4. Capable of giving signed informed consent/assent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol |
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E.4 | Principal exclusion criteria |
Medical Conditions
1. Participant 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 at Screening that in the investigator’s/designee’s opinion may interfere with study objectives (eg, expose participant to unacceptable risk by study participation, confound evaluation of treatment response or AEs, or interfere with participant’s ability to complete the study)
2. Participant has unstable AD or any consistent requirement for high-potency TCS to manage AD signs and symptoms
3. Participant 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 study intervention 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 including the following:
a. For participants 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 Columbia Suicide Severity Rating Scale (C-SSRS) (Section 8.2.6) or a previous history of suicidal behaviors in their lifetime:
“Yes” answer to any of the suicidal behavior items of the C-SSRS.
b. For participants ≥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 (Section 8.2.6) 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. Participant 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).
6. Participant has a history of angioedema or anaphylaxis to topical products or known sensitivity to any of the components of the IPs.
7. Participant has a known lack of efficacy to crisaborole.
Prior/Concomitant Therapy
8. Participant has a history of use of biologic therapy including intravenous immunoglobulin or dupilumab at any time prior to study
9. Participant has recent or anticipated concomitant use of systemic therapies or therapies that might alter the course of AD, as specified in the protocol
10. Participant has received any of the prohibited medications/therapies that may alter the course of AD without the required minimum washout period (see Section 6.5.1) or anticipated concomitant use of any of the prohibited medications/therapy (see Section 6.5.2).
11. Participant has any planned surgical or medical procedure that would overlap with study participation, from Screening through the end of study.
Prior/Concurrent Clinical Study Experience
12. Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
Diagnostic assessments
13. Other acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or study intervention 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.
Other Exclusions
14. Pregnant female participants, breastfeeding female participants, and female participants 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 study intervention.
15. 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 participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Flare-free maintenance until onset of first flare during the 52-week double-blind period
- Incidence of treatment emergent adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary endpoints during the 52-week double-blind period:
- Number of flare-free days
- Number of flares
- Pruritus response maintenance until onset of first flare
Other secondary endpoints during the 52-week double-blind period:
* ≥50% reduction in Eczema Area and Severity Index (EASI)50 response maintenance
* Maintenance of Dermatology Quality of Life Assessments
* Maintenance of Patient Oriented Eczema Measure (POEM)
The following will be assessed during flare treatment period:
- Severity of flare on Investigator’s Static Global Assessment (ISGA) and EASI
- Duration of flare episode
The following will be assessed as change from baseline of each respective treatment period (run-in, double-blind, and flare treatment):
- EASI scores
- ISGA scores
- Treatable AD %BSA
- Most commonly affected AD %BSA
The following patient reported outcomes (PROs) will be assessed:
- Night Time Itch
- AD Skin Pain
- Patient Global Impression of Severity
- Patient Global Impression of Change
- Medical Outcomes Study Sleep Scale
- EuroQoL EQ-5D
- Work and Classroom Productivity
- Hospital Anxiety and Depression |
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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 | 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 | 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 | 2 |
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 | 18 |
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 |
Australia |
Austria |
Canada |
China |
France |
Israel |
Spain |
Turkey |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 20 |