A Study to Learn About the Study Medicine Etrasimod in Adults With Moderate to Severe Atopic Dermatitis (AD) Who Have Already Tried Treatments Taken by Mouth or by Injection

Study Overview
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Brief Summary
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The purpose of this study is to learn about the safety and effects of the study medicine called etrasimod for the possible treatment of atopic dermatitis (AD), also called eczema, in adults who have already tried AD treatments taken by mouth or by injection that work all over the body. These adults can have moderate to severe AD. This study is seeking participants who: have AD for at least 1 year have moderate-to-severe AD have tried treatments that work all over the body and saw no effects are willing to apply a moisturizer at least once daily during the study This is a 2-part study that is only selecting about 60 participants for Part 1 as of now. In Part 1, half of the participants will receive etrasimod, a pill to be taken by mouth once daily. The other half will receive a placebo, a pill that looks like etrasimod but has no medicine also taken by mouth once daily. No one will know what treatment the participant is taking. The Sponsor will compare participant experiences of those taking etrasimod to those taking placebo for 16 weeks. This will help determine if the study medicine is safe and effective. After the first 16 weeks, some participants may continue the study knowing they are taking etrasimod for an additional 52 weeks. Those participating for just the first 16-weeks, will need to visit the study clinic at least 6 times during the study (about every 4 weeks), and will have to come for 2 safety follow up visits at 2nd and 4th week after the last dose of study medicine. People who want to and can continue for an additional 52 weeks will need to visit the study clinic for at least 6 more visits making 12 total visits over 68 weeks followed by 2 safety follow up visits at the 2nd and 4th week after the last dose of study medicine. In Part 2 of the study, around 340 more participants will be participating. Everyone will receive etrasimod pills once daily for 52 weeks. Participants will need to go to the study clinic at least 9 times after which they will have to go for 2 more safety follow up visits at the 2nd and 4th weeks after the last dose of study medicine. At every study visit in Part 1 and Part 2, the focus will be on signs and symptoms of AD (like lesions, itch, and pain) as well as general health and overall side effects. Blood samples and vital signs will be taken at every visit. Due to the way the study medicine works, the in-study clinic visit will last at least 4 hours on Day 1 (Part 1 and Part 2) and Week 16 (Part 1).

Official Title
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A PHASE 2/3, TWO-PART STUDY TO EVALUATE THE EFFICACY AND LONG-TERM SAFETY WITH ORAL ETRASIMOD, 2 MG, ONCE DAILY IN ADULT PARTICIPANTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS WITH A HISTORY OF PRIOR SYSTEMIC TREATMENT FAILURE

Conditions
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Atopic Dermatitis, Atopic Dermatitis, Unspecified, Eczema, Eczema, Atopic

Intervention / Treatment
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* Drug: etrasimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must meet the following key inclusion criteria to be eligible for enrollment into the study: 1. Age 18-80 at screening (or minimum age of consent according to local regulations). 2 Chronic AD (also known as atopic eczema) that was diagnosed at least 1 year prior to Screening and meets Hanifin and Rajka criteria at screening).1 3. Moderate to severe AD: IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 = moderate and 4 = severe) at screening and baseline (Day 1) BSA ≥10% of AD involvement at screening and baseline (Day 1) Eczema Area and Severity Index (EASI) ≥16 at screening and baseline (Day 1) 4. A participant who has failed a prior systemic therapy for AD, ie, refractory, moderate-to-severe AD that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable. 5. Willing to apply a topical emollient/moisturizer at least once daily for ≥1 week prior to baseline (Day 1) and willing to maintain consistent (ie, no change in type, frequency, or application) daily application over the course of the study. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: Presence of confounding factors: Skin conditions (eg, psoriasis, seborrheic dermatitis) that may interfere with evaluation of AD or assessment of treatment response as deemed by the investigator. Current significant active infection or requiring a treatment for infection that may interfere with the assessment of AD. Hypersensitivity to etrasimod or any of the excipients. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1: Approximately 60 participants with moderate-to-severe AD with a history of prior systemic treatment failure will be randomized (1:1 ratio) in a double blind (DB) manner to receive etrasimod 2 mg or placebo orally, once daily, for 16 weeks. Randomization will be stratified by disease severity as measured by IGA score (3 [moderate AD], 4 [severe AD]) at baseline. After DB period, participants may be given the option to continue in an open label extension (OLE) phase whereby they will receive etrasimod 2 mg (tablet) for up to an additional 52 weeks. Part 2: Approximately 340 additional participants will be enrolled to receive etrasimod 2 mg orally, once daily, for 52 weeks in an open-label manner.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: etrasimod<br>2 mg, oral tablet, once daily | Drug: etrasimod<br>* PART 1 Double Blind one 2 mg tablet once daily for up to 16 weeks PART 1 Open Label Extension one 2 mg tablet once daily for an additional 52 weeks PART 2 Open Label one 2 mg tablet once daily for up 52 weeks<br>* Other names: PF-07915503;|
| Placebo Comparator: Placebo (Part 1 DB period only)<br>Oral sham comparator | Drug: Placebo<br>* PART 1 DOUBLE BLIND Placebo - one table daily for up to 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 DB: Proportion of participants achieving IGA of clear (0) or almost clear (1) (on a 5-point scale) and a reduction of ≥ 2 points from baseline | To evaluate the efficacy of etrasimod, 2 mg, QD versus placebo | at Week 16 | 
| Part 1 OLE and Part 2: Incidence and severity of treatment-emergent adverse events (AEs), AEs leading to study treatment discontinuation, serious AEs, and AEs of special interest. | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Hemoglobin (g/dL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in RBC (x10^6/uL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Platelets, WBC, and WBC with Diff (x10^3/uL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in TBNK panel (abs/uL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Hematocrit, WBC with Diff, TBNK with Diff (%) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Total bilirubin, Urea Nitrogen, Creatinine (mg/dL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in AP, ALT (SGPT), AST (SGOT) (U/L) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Total Protein and Albumin-BCG (g/dL) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in Serum Sodium, Serum Potassium (mmol/L) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in urinalysis (pos/neg local dipstick) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in vital sign values (BP) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in vital sign values (pulse rate) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in vital sign values (temperature) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in vital sign values (respiratory rate) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in ECG measurements (QT interval) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in ECG measurements (QTc interval) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in ECG measurements (heart rate) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in ECG measurements (PR interval) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 
| Part 1 OLE and Part 2: Incidence of clinically significant changes in ECG measurements (QRS complex) | To evaluate the long-term safety of oral etrasimod, 2 mg, QD | Baseline up to 68 weeks in Part 1 and up to 52 weeks in Part 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 DB: Proportion of participants achieving a EASI-75 | To evaluate the efficacy of etrasimod, 2 mg, QD based on additional measures | at Week 16 | 
| Part 1 DB: Percent change from baseline in EASI | To evaluate the efficacy of etrasimod, 2 mg, QD based on additional measures | at Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Failure, Oral