Atopic Dermatitis
Conditions
Brief summary
This Phase 2a trial will evaluate the effects of EP262 in subjects with atopic dermatitis
Interventions
DRUGOral EP262
Once daily
DRUGPlacebo
Once Daily
Sponsors
Escient Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Clinically confirmed diagnosis of active atopic dermatitis for at least 1 year * BSA of 3% to 20% and a vIGA-AD score of ≥3
Exclusion criteria
* Other active skin diseases associated with chronic pruritus * Clinically infected atopic dermatitis that requires antibiotic therapy * Use of specific treatments for atopic dermatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to Week 10 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A TEAE is defined as an adverse event (AE) with an onset after the first dose of study drug or an existing event that worsened after the first dose during the study. |
| Number of Participants With Any ≥Grade 3 TEAE | up to Week 10 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A TEAE is defined as an adverse event (AE) with an onset after the first dose of study drug or an existing event that worsened after the first dose during the study. AEs were graded for severity using the the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v.5). CTCAE grades were scored as: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life threatening; Grade 5 = death related to the AE. |
| Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs | up to Week 10 | Clinical meaningfulness was determined by the investigator. |
| Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiograms (ECGs ) | up to Week 10 | Clinical meaningfulness was determined by the investigator. |
| Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Hematology, Chemistry, or Coagulation Parameters | up to Week 10 | Clinical meaningfulness was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change From Baseline to Week 6 in Gene Expression Signature and Skin Histology (Epidermal Thickness, Immune Cell Infiltration, Markers of Epidermal Proliferation) as Assessed From Biopsies of Lesional Skin | Baseline; Week 6 | Biopsies were taken from lesional and nonlesional skin, and differential gene expression was analyzed by comparing lesional samples at baseline and Week 6 to nonlesional reference samples at baseline. Genes were classified as differentially expressed if they met 2 criteria: an absolute log2 fold change greater than 1.5 and an adjusted p-value less than 0.05 using Wilcoxon signed rank test or paired Students t-test and Bonferroni correction. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study was conducted in the United States and Canada.
Participants by arm
| Arm | Count |
|---|---|
| 150 mg EP262 QD Participants received oral EP262 150 milligrams (mg) QD during the 6-week Double-blind Treatment Period. After administration of the last dose, participants entered a 4-week Follow-up Period. | 21 |
| Placebo QD Participants received matching oral placebo once daily (QD) during the 6-week Double-blind Treatment Period. After administration of the last dose, participants entered a 4-week Follow-up Period. | 11 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incarceration | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | 150 mg EP262 QD | Placebo QD | Total |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 16.54 | 41.7 years STANDARD_DEVIATION 11.3 | 40.3 years STANDARD_DEVIATION 14.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 11 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 7 Participants | 22 Participants |
| Sex: Female, Male Female | 14 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 21 |
| other Total, other adverse events | 7 / 11 | 2 / 21 |
| serious Total, serious adverse events | 0 / 11 | 0 / 21 |
Outcome results
Primary
Number of Participants With Any ≥Grade 3 TEAE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A TEAE is defined as an adverse event (AE) with an onset after the first dose of study drug or an existing event that worsened after the first dose during the study. AEs were graded for severity using the the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v.5). CTCAE grades were scored as: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life threatening; Grade 5 = death related to the AE.
Time frame: up to Week 10
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With Any ≥Grade 3 TEAE | 0 Participants |
| Placebo QD | Number of Participants With Any ≥Grade 3 TEAE | 0 Participants |
Primary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. A TEAE is defined as an adverse event (AE) with an onset after the first dose of study drug or an existing event that worsened after the first dose during the study.
Time frame: up to Week 10
Population: Safety Analysis Set: all participants who were randomized and took at least 1 dose of randomized study drug. Safety analyses were based upon treatment actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| Placebo QD | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 7 Participants |
Primary
Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Hematology, Chemistry, or Coagulation Parameters
Clinical meaningfulness was determined by the investigator.
Time frame: up to Week 10
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Hematology, Chemistry, or Coagulation Parameters | 0 Participants |
| Placebo QD | Number of Participants With Clinically Meaningful Changes From Baseline in Clinical Hematology, Chemistry, or Coagulation Parameters | 0 Participants |
Primary
Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiograms (ECGs )
Clinical meaningfulness was determined by the investigator.
Time frame: up to Week 10
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiograms (ECGs ) | 1 Participants |
| Placebo QD | Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiograms (ECGs ) | 1 Participants |
Primary
Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs
Clinical meaningfulness was determined by the investigator.
Time frame: up to Week 10
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs | 0 Participants |
| Placebo QD | Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With a Change From Baseline to Week 6 in Gene Expression Signature and Skin Histology (Epidermal Thickness, Immune Cell Infiltration, Markers of Epidermal Proliferation) as Assessed From Biopsies of Lesional Skin
Biopsies were taken from lesional and nonlesional skin, and differential gene expression was analyzed by comparing lesional samples at baseline and Week 6 to nonlesional reference samples at baseline. Genes were classified as differentially expressed if they met 2 criteria: an absolute log2 fold change greater than 1.5 and an adjusted p-value less than 0.05 using Wilcoxon signed rank test or paired Students t-test and Bonferroni correction.
Time frame: Baseline; Week 6
Population: Full Analysis Set: all participant who were randomized and took at least 1 dose of randomized study drug. Participants were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 150 mg EP262 QD | Number of Participants With a Change From Baseline to Week 6 in Gene Expression Signature and Skin Histology (Epidermal Thickness, Immune Cell Infiltration, Markers of Epidermal Proliferation) as Assessed From Biopsies of Lesional Skin | 0 Participants |
| Placebo QD | Number of Participants With a Change From Baseline to Week 6 in Gene Expression Signature and Skin Histology (Epidermal Thickness, Immune Cell Infiltration, Markers of Epidermal Proliferation) as Assessed From Biopsies of Lesional Skin | 0 Participants |