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

Phase 2

Terminated

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

Interventions: Drug: Placebo
Drug: etrasimod

Registration Number: NCT05732454

Lead Sponsor: Pfizer

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Participants must meet the following key inclusion criteria to be eligible for enrollment into the study:

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.
1. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (Part 1 DB period only)	Placebo	Oral sham comparator
etrasimod	etrasimod	2 mg, oral tablet, once daily

Primary Outcome Measures

Name	Time	Method
Part 1, DB Period: Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response at Week 16	DB Period: Week 16	IGA measured AD severity, based on a 5-point scale (0-4); 0= AD is clear, 1= AD is almost clear, 2= mild AD, 3= moderate AD and 4= severe AD. IGA response was defined as participants achieving IGA 0 (clear) or 1 (almost clear) and a reduction of \>=2 points from baseline.
Part 1, DB Period: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (All Causality)	DB Period: From first dose of study drug up to 16 Weeks of treatment	An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state.
Part 1, DB Period: Number of Participants With TEAEs (All Causality) Leading to Study Treatment Discontinuation	DB Period: From first dose of study drug up to 16 Weeks of treatment	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state.
Part 1, OLE Period: Number of Participants With Markedly Abnormal 12-Lead Electrocardiogram Measurements and AV Blocks	OLE Period: Day 169/Week 24	Standard 12-lead ECGs utilizing limb leads were used to measure PR interval, QT interval, QTcF, and QRS complex. Number of participants with non-zero ECG abnormalities and AV blocks are reported in this outcome measure.
Part 1, OLE Period: Number of Participants With Markedly Abnormal Vital Sign	OLE Period: Day 141/Week 20; Day 169/Week 24; Day 281/Week 40; Follow Up 1; Follow Up 2	Vital signs evaluation included SBP, DBP, pulse rate. Number of participants with non-zero vital signs abnormalities are reported in this outcome measure.
Part 1, DB Period: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) (All Causality)	DB Period: From first dose of study drug up to 16 Weeks of treatment	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of death); new or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medical events judged by investigator.
Part 1, DB Period: Number of Participants With Treatment Emergent AEs of Special Interest (AESIs) (All Causality)	DB Period: From first dose of study drug up to 16 Weeks of treatment	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state. AESIs included here were cardiovascular events (i.e., bradycardia, Atrioventricular (AV) conduction delay, and hypertension); macular edema, pulmonary events (airflow obstruction or decreased gas exchange); infections (severe infections, opportunistic infections \[including progressive multifocal leukoencephalopathy (PML)\], Herpes simplex and Herpes zoster); liver injury (liver transaminase elevation and bilirubin elevation); posterior reversible encephalopathy syndrome (PRES) and malignancies.
Part 1, DB Period: Number of Participants With Laboratory Test Abnormalities	DB Period: From first dose of study drug up to 16 Weeks of treatment	Laboratory assessments included hematology, clinical chemistry, urinalysis, other parameters and reflex tests. Number of participants with abnormalities in any of laboratory parameters is reported.
Part 1, DB Period: Number of Participants With Markedly Abnormal 12-Lead Electrocardiogram Measurements and AV Blocks	DB Period: Pre-dose and 4 hours (hrs) post-dose on Day 1/Week 0; Pre-dose and 4 hrs post-dose on Day 113/Week 16	Standard 12-lead ECGs utilizing limb leads were used to measure PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF), and QRS complex. Number of participants with non-zero ECG abnormalities and AV blocks are reported in this outcome measure.
Part 1, DB Period: Number of Participants With Markedly Abnormal Vital Sign	DB Period: Pre-dose and 1, 2, 3, 4 hours (hrs) post-dose on Day 1/Week 0; Day 29/Week 4; Day 57/Week 8; Day 85/Week 12; Pre-dose and 1, 2, 3, 4, 5 and 6 hrs post-dose on Day 113/Week 16	Vital signs evaluation included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate. Number of participants with non-zero vital signs abnormalities are reported in this outcome measure.
Part 1, OLE Period: Number of Participants With TEAEs (All Causality)	OLE Period: First dose of study drug in OLE period up to 4 weeks after last dose in OLE period (up to maximum of 56 Weeks)	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state.
Part 1, OLE Period: Number of Participants With Treatment Emergent AEs (All Causality) Leading to Study Treatment Discontinuation	OLE Period: First dose of study drug in OLE period up to 4 weeks after last dose in OLE period (up to maximum of 56 Weeks)	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state.
Part 1, OLE Period: Number of Participants With Treatment Emergent SAEs (All Causality)	OLE Period: First dose of study drug in OLE period up to 4 weeks after last dose in OLE period (up to maximum of 56 Weeks)	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of death); new or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic or other medical events judged by investigator.
Part 1, OLE Period: Number of Participants With Treatment Emergent AESIs (All Causality)	OLE Period: First dose of study drug in OLE period up to 4 weeks after last dose in OLE period (up to maximum of 56 Weeks)	An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent are events between first dose of study drug and up to last dose that were absent before treatment or that worsened relative to pretreatment state. AESIs included here were cardiovascular events (i.e., bradycardia, AV conduction delay, and hypertension); macular edema, pulmonary events (airflow obstruction or decreased gas exchange); infections (severe infections, opportunistic infections \[including PML\], Herpes simplex and Herpes zoster); liver injury (liver transaminase elevation and/or bilirubin elevation); PRES and malignancies.
Part 1, OLE Period: Number of Participants With Laboratory Test Abnormalities	OLE Period: First dose of study drug in OLE period up to 4 weeks after last dose in OLE period (up to maximum of 56 Weeks)	Laboratory assessments included hematology, clinical chemistry, urinalysis, other parameters and reflex tests. Number of participants with abnormalities in any of laboratory parameters is reported.

Secondary Outcome Measures

Name	Time	Method
Part 1, DB Period: Percentage of Participants Who Achieved >=75% Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-75) at Week 16	DB Period: Week 16	EASI-75 response was defined as a 75% reduction or greater in EASI score from Baseline to Week 16. EASI quantified severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema \[E\], induration/papulation \[I\], excoriation \[Ex\] and lichenification \[L\]) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\Ah\(Eh+Ih+Exh+Lh) + 0.2\Au\(Eu+Iu+ExU+Lu) + 0.3\At\(Et+It+Ext+Lt) + 0.4\Al\(El+Il+Exl+Ll); A = EASI area score; h = head and neck; u = upper limbs; t = trunk; l = lower limbs.
Part 1, DB Period: Percent Change From Baseline in EASI Score at Week 16	DB Period: Baseline, Week 16	EASI quantified severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema \[E\], induration/papulation \[I\], excoriation \[Ex\] and lichenification \[L\]) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\Ah\(Eh+Ih+Exh+Lh) + 0.2\Au\(Eu+Iu+ExU+Lu) + 0.3\At\(Et+It+Ext+Lt) + 0.4\Al\(El+Il+Exl+Ll); A = EASI area score; h = head and neck; u = upper limbs; t = trunk; l = lower limbs.

Trial Locations

Locations (74): Tory Sullivan, Md Pa
🇺🇸
North Miami Beach, Florida, United States
CaRe Clinic
🇨🇦
Red Deer, Alberta, Canada
Pratia Pardubice a.s.
🇨🇿
Pardubice, Czechia
Eyemed
🇵🇱
Lublin, Lubelskie, Poland
Nzoz Specjalistyczny Ośrodek Dermatologiczny "Dermal"
🇵🇱
Bialystok, Podlaskie, Poland
First OC Dermatology Research Inc
🇺🇸
Fountain Valley, California, United States
Jared R. Younger, MD (Ophthalmologist)
🇺🇸
Fountain Valley, California, United States
Bryan D. Vo. MD (Pulmonologist)
🇺🇸
Laguna Hills, California, United States
California Allergy and Asthma Medical Group
🇺🇸
Los Angeles, California, United States
Dr. Carolyn M. Wong
🇺🇸
Los Angeles, California, United States
Dr. Gerald Markovitz
🇺🇸
Los Angeles, California, United States
Resolution Advanced Imaging Center
🇺🇸
Santa Monica, California, United States
Ponce PFT & Medical services, INC [for pulmonology examination]
🇺🇸
Aventura, Florida, United States
Advanced Eye Center: Rodrigo Belalcazar, MD
🇺🇸
Hialeah, Florida, United States
Direct Helpers Research Center
🇺🇸
Hialeah, Florida, United States
Gsi Clinical Research
🇺🇸
Margate, Florida, United States
Randy Burks, MD, FACS
🇺🇸
Margate, Florida, United States
D & H National Research Centers, Inc.
🇺🇸
Miami, Florida, United States
Imaging - Advanced Health Imaging
🇺🇸
Miami, Florida, United States
The Selem Center [Ophthalmologist JOSEPH SELEM]
🇺🇸
Miami, Florida, United States
Miami Dermatology and Laser Research
🇺🇸
Miami, Florida, United States
Ophthalmology - Dr. Edward Boshnick's Global Vision Rehabilitation Center
🇺🇸
Miami, Florida, United States
Pulmonology - Miami Pulmonology Specialists
🇺🇸
Miami, Florida, United States
Pelletier Jesse MD
🇺🇸
North Miami Beach, Florida, United States
Santos Carlos R MD
🇺🇸
North Miami Beach, Florida, United States
Gateway Radiology
🇺🇸
Pinellas Park, Florida, United States
Hull & Hull Medical Specialists
🇺🇸
Plantation, Florida, United States
GCP Research, Global Clinical professionals
🇺🇸
Saint Petersburg, Florida, United States
St. Anthonys Hospital
🇺🇸
Saint Petersburg, Florida, United States
USF Health
🇺🇸
Tampa, Florida, United States
Lung and Sleep Disorder Center
🇺🇸
Lathrup Village, Michigan, United States
Revival Research Institute, LLC
🇺🇸
Troy, Michigan, United States
Somerset Opthalmology PC
🇺🇸
Troy, Michigan, United States
Eye Institute
🇺🇸
Tulsa, Oklahoma, United States
Pulmonary and Sleep Center of Oklahoma
🇺🇸
Tulsa, Oklahoma, United States
Vital Prospects Clinical Research Institute, PC
🇺🇸
Tulsa, Oklahoma, United States
Monument Health Rapid City Hospital
🇺🇸
Rapid City, South Dakota, United States
Health Concepts
🇺🇸
Rapid City, South Dakota, United States
In Vision Optical and Eyecare
🇺🇸
Rapid City, South Dakota, United States
Eye Care Associates of Arlington
🇺🇸
Arlington, Texas, United States
Arlington Research Center
🇺🇸
Arlington, Texas, United States
Texas Pulmonary
🇺🇸
Arlington, Texas, United States
Alpesh D. Desai, DO PLLC
🇺🇸
Houston, Texas, United States
Becky Fredrickson, MD [Optometrist/Ophthalmologist]
🇺🇸
Houston, Texas, United States
Rupesh Vakil, MD [Pulmonologist]
🇺🇸
Houston, Texas, United States
Acclaim Dermatology
🇺🇸
Sugar Land, Texas, United States
Horizon Eye Care and Optical
🇺🇸
Sugar Land, Texas, United States
Sweetwater Pulmonary Associates
🇺🇸
Sugar Land, Texas, United States
Rejuvenation Dermatology
🇨🇦
Edmonton, Alberta, Canada
Visique
🇨🇦
Québec, Quebec, Canada
Biron
🇨🇦
Quebec, Canada
Alpha Recherche Clinique
🇨🇦
Quebec, Canada
Poliklinika VEKTOR Pardubice
🇨🇿
Pardubice, Czechia
Fakultní nemocnice v Motole
🇨🇿
Praha 5, Czechia
Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak Spółka Partnerska
🇵🇱
Wroclaw, Dolnośląskie, Poland
Artemed Centrum Medyczne
🇵🇱
Wrocław, Dolnośląskie, Poland
Specjalistyczna Praktyka Lekarska Joanna Kalinowska
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Wrocław, Dolnośląskie, Poland
Indywidualna Specjalistyczna Praktyka Lekarska Michał Silber
🇵🇱
Wrocław, Dolnośląskie, Poland
DERMEDIC Iwona Zdybska
🇵🇱
Lublin, Lubelskie, Poland
Centrum Medyczne ,,All - Med'' Badania Kliniczne
🇵🇱
Kraków, Małopolskie, Poland
Centrum Medyczne Dietla 19
🇵🇱
Kraków, Małopolskie, Poland
AUGON Gabinet Okulistyczny
🇵🇱
Bialystok, Podlaskie, Poland
Gabinet Alergologiczny IR-med dr n. med. Izabela Roszko-Kirpsza
🇵🇱
Bialystok, Podlaskie, Poland
Flosmed
🇵🇱
Poznan, Wielkopolskie, Poland
Niepubliczny Zakład Opieki Zdrowotnej Zespół Poradni Specjalistycznych "Termedica"
🇵🇱
Poznan, Wielkopolskie, Poland
Medoculis
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Poznań, Wielkopolskie, Poland
Medicus
🇵🇱
Szczecin, Zachodniopomorskie, Poland
Twoja Przychodnia SCM
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Szczecin, Zachodniopomorskie, Poland
Gabinety Lekarskie Rivermed
🇵🇱
Poznan, Poland
Centrum Medyczne Szpital Świętej Rodziny
🇵🇱
Łódź, Łódzkie, Poland
Dermoklinika - Centrum Medyczne spółka cywilna M. Kierstan, J. Narbutt, A. Lesiak
🇵🇱
Łódź, Łódzkie, Poland
Ekovivus
🇵🇱
Łódź, Łódzkie, Poland
Centrum Medyczne Angelius Provita
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Katowice, Śląskie, Poland
Centrum Zdrowia Ochaliczówka
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Katowice, Śląskie, Poland