E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe atopic dermatitis (AD) |
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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 provide access to abrocitinib to adolescent and adult patients with or without background topical therapy who have inadequate treatment options due to inadequate response or intolerance to available approved medicated topical and systemic therapies and need abrocitinib as a possible treatment regimen for moderate to severe AD. |
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E.2.2 | Secondary objectives of the trial |
To gain additional safety and tolerability data for abrocitinib 100 mg and 200 mg once daily (QD) with or without background topical therapy in adolescent and adult participants with moderate to severe AD in a ‘real world’ clinical setting.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
Age:
1. Participants 12 years of age or older at the time of signing the informed consent. Adolescent participants below the age of 18 years(or country -specific age of majority) will only be enrolled if approved by the country regulatory/health authority. If these approvals have not been granted, only participants 18 years of age (or country-specific age of majority) or older at the time of signing of informed consent may be enrolled.
2. Participants who meet all of the following atopic dermatitis criteria:
- Clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for at least 6months prior to Day 1 and has confirmed atopic dermatitis at the Screening and Baseline visits according to Hanifin and Rajka criteria for AD.10 Refer to protocol. -Inadequate treatment options for moderate to severe AD due to history of inadequate response or intolerance to treatment with available approved medicated topical and systemic therapies for the treatment of AD, underlying conditions that preclude use of available approved medicated topical and systemic therapies for the treatment of AD, or lack of availability or access to approved medicated topical and systemic therapies for the treatment of AD.
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 prescribed product).
- Moderate to severe AD as indicated by meeting at least 1of the following on the day of the baseline visit: IGA ≥3; EASI ≥16.
3. Participants who are ineligible for participation in any ongoing clinical trial of abrocitinib, including lack of access due to geographical limitations.
4. Participants and, as applicable, parents/legal guardians of age of minority participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Sex:
5. 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. Refer to protocol.
a. Male participants: No contraceptive measures are required.
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) (Refer to the definition in the Contraceptive Guidance appendix).
OR
- Is a WOCBP.A WOCBP who is sexually active must use a contraceptive method that is highly effective, with a failure rate of <1%, as described in Contraceptive Guidanceappendixduring theintervention period and for at least 28 days after the last dose of abrocitinib. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of abrocitinib.
- A WOCBP must have a negative highly sensitive(refer to the Clinical Laboratory Tests appendix)serum pregnancy test at the Screening visit. A urine pregnancy test with a sensitivity of at least 25 mIU/mL, will be performed before the first dose of abrocitinib and at every site visit including the EOT and Follow-up/EOS visits to confirm the participant has not become pregnant. 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.
- 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.
Please refer to section 5.1 of the protocol for a complete list of inclusion criteria |
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E.4 | Principal exclusion criteria |
Medical Conditions:
1. Other medical or psychiatric condition including recent(within the past year)or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. The participant must have a risk assessment done by a qualified mental health professional (MHP) to assess whether it is safe to participate in the trial if the participant’s responses on any of the screening instruments or other information from the screening period indicate:
- Suicidal ideation associated with actual intent and a method or plan in the past year for adults or at any time in their lifetime for adolescents ages ≥12 and <18years: “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 for adults or at any time in their lifetime for adolescents ages ≥12 and <18 years: “Yes” answer (in the past 5 years for adults or at any time in their lifetime for adolescents) to any of the suicidal behavior items of the C-SSRS.
- Any lifetime history of serious or recurrent suicidal behavior (non-suicidal self-injurious behavior is not a trigger for a risk assessment unless in the investigator’s judgement it is indicated).
- Clinically significant depression: Patient Health Questionnaire 8 items (PHQ-8) when the total score is≥15 for adults or≥10for adolescents ages ≥12 and <18years.
- The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria.
- In the investigator’s judgment a risk assessment or exclusion is required.
3. Have increased risk of developing venous thromboembolism, eg, deep vein thrombosis or pulmonary embolism:
- History of venous thromboembolism, or
- First-degree relative with unprovoked venous thromboembolism (ie, without known underlying cause such as trauma, surgery, immobilization, prolonged travel, pregnancy, hormone use, or plaster cast), that would suggest participant is at increased risk of inherited coagulation disorder (eg,Factor V Leiden).
4. A current or past medical history of conditions associated with thrombocytopenia, coagulopathy, or platelet dysfunction.
5. Receiving anti-coagulants or medications known to cause thrombocytopenia (unless considered safe to stop and washout for the duration of the study).
6. Have a history of any lymphoproliferative disorder such as Epstein Barr virus (EBV), related lymphoproliferative disorder, history of lymphoma, leukemia, or signs or symptoms suggestive of current lymphatic or lymphoid disease.
7. Infection history:
- Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6months prior to Day1;
- Have active chronic or acute skin infection requiring treatment with systemic antimicrobials within 2weeks prior to Day1, or superficial skin infections within 1week prior to Day1;
- A participant known to be infected with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C.
• Screening for Hepatitis B will include testing for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb). Participants who are HBsAg negative and HBcAb positive will have testing for HBsAb. Participants who are HBsAg negative, HBcAb positive, and HBsAb positive at Screening will have testing for hepatitis B Virus (HBV) deoxyribonucleic acid (DNA). Participants who have HBV DNA above the lower limit of quantification (LLQ) are excluded. Participants who have HBV DNA negative or below LLQ may be assigned to abrocitinib on Study Day 1 but will have HBV DNA testing repeated at the Q12 week visits, at the End of Treatment (EOT) visit, and at the Follow-up/End of Study visit
8. Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
9. Have a known immunodeficiency disorder.
10. Have a history of alcohol or substance abuse within 6 months prior to Day 1 that in the opinion of the investigator will preclude participation in the study.
Please refer to section 5.2 of the protocol for a complete list of exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
Secondary Endpoints :
All participants who receive abrocitinib (safety population) will be included in the safety analyses. All safety data will be summarized descriptively. Safety endpoints for the study include:
•Treatment emergent AEs and SAEs;
•Withdrawals from active treatment due to AEs and SAEs;
•Serious infections, defined as any infection (viral, bacterial, and fungal) requiring hospitalization or parenteral antimicrobials.
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 23 |
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 |
Mexico |
Saudi Arabia |
Turkey |
Austria |
Belgium |
Canada |
Greece |
Italy |
Netherlands |
Russian Federation |
Spain |
Switzerland |
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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The study will terminate for all participants enrolled in a country when abrocitinib becomes commercially available in that country or until the sponsor terminates the study in that country. The end of the study is defined as the date of the last scheduled procedure as shown in the Summary of Activities for the last participant in the trial globally. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |