Atopic Dermatitis
Conditions
Keywords
eczema
Brief summary
This is a randomized double-blind/placebo study evaluate the efficacy of ASN002 in subjects with moderate to severe atopic dermatitis (AD).
Detailed description
This is a placebo controlled study where subjects with moderate to severe atopic dermatitis will be randomized (1:1:1:1) to receive ASN002 at 40 mg, 60 mg, or 80 mg, or placebo once daily for 12 weeks. Eligible subjects will get the opportunity to enroll in the 24 month open-label extension study (OLE). There will be a 4-week follow up period for subjects not participating in the OLE study. This study will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling and three or four biopsies from subjects who consent.
Interventions
DRUGASN002
Daily dose of ASN002 for 12 weeks
DRUGPlacebo Oral Tablet
Placebo of ASN002 for 12 weeks
Sponsors
Asana BioSciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained prior to any study-related procedure being performed; * Male or female, 18≤ years and ≤75 years of age with chronic AD for at least 6 months. * At least 10% body surface area (BSA) of AD involvement at the baseline visits * Has a body mass index (BMI) ≤35 kg/m2 * History of inadequate response to topical corticosteroids or calcineurin inhibitors as treatment for AD within 1 year before the screening visit. * Willing to apply only a basic bland emollient once or twice-daily for at least 7 days before the baseline visit. * Willing to comply with discontinuation of certain treatments for AD, as directed by the Investigator. * Willing to use medically effective methods of birth control * Females of reproductive potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1.. * Willing and able to comply with clinic visits and study-related procedures
Exclusion criteria
* Clinically infected atopic dermatitis. * Presence of any of the following laboratory abnormalities at the screening visit: Hemoglobin \< 11 g/dL, White blood cell (WBC) \< 3.0 x 103 /μL, Platelet count \< 125 x 103 /μL, Neutrophils \< \< 2.50 x 103 /μL, Lymphocytes ≤ 1.2 x 103 /μL, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 1.5 x the upper limit of normal (ULN),Total bilirubin \> ULN (except for elevated indirect bilirubin secondary to Gilbert's syndrome), Creatinine \> ULN * A serious uncontrolled condition including hypertension, history of tuberculosis, hepatitis B or C infection, immune deficiency, heart disease, heart conduction disorder, diverticulitis, diabetes, reflux disease requiring protocol pump inhibitor therapy, malabsorption syndrome, or cancer. * Any condition requiring the use of anticoagulants. * History of hypertrophic scarring or keloid formation in scars or suture sites. * Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the patient at risk, interfere with participation in the study, or interfere with the interpretation of study results * Pregnant or breast-feeding women * Known hypersensitivity to ASN002 or its excipients; * Prior treatment with SYK or JAK inhibitors for which the subject received no clinical benefit, or the subject relapsed whilst on therapy. * Has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1. * Planned major surgical procedure during the length of the patient's participation in this study * There will be a waiting period of 4 weeks before receiving the first does for anyone who has used oral or intravenous treatments (other than biologics) that could affect atopic dermatitis, received a non-biological investigational product or device, excessive sun exposure, is planning a trip to a sunny climate, or has used tanning booths, or received or plans to receive a live attenuated vaccine one four weeks after the last day of taking the drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | Week 12 | The Eczema Area and Severity Index (EASI) is a composite score ranging from 0 to 72, the higher the value the worse the disease, that takes into account the degree of erythema, induration/infiltration (papules), excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the percentage of BSA involved for each body region and for the proportion of the body region to the whole body. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 5-D Pruritus (Itching) Scale | Week 12 | The 5-D Pruritus Scale is a 1-page, 5-question, validated questionnaire used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; subjects rated their symptoms over the preceding 2-week period as present or on a 1 to 5 scale, with 5 being the most affected. The total score of 5-D pruritus is a sum of the 5 scores to provide a total score range from 5 (best) to 25 (worst). |
| Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | Week 12 | In the SCORAD grading system, six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) evaluate the Atopic Dermatitis severity. The overall body surface area affected by atopic dermatitis was evaluated (from 0% to 100%) and included in the SCORAD scores. Loss of sleep and pruritus were evaluated by subjects on a visual analog scale (0-10) and were based on the average of the last three days/nights. The sum of these measures represented the SCORAD, which could range from 0 to 103. The higher the score the more severe the disease. |
| Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1 | Week 12 | The IGA is a global assessment of the current state of the disease. It is a 5-point (0-4) morphological assessment of overall disease severity. The 0 is the least severe and 4 is the most severe. |
| Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75) | Week 12 | Percent of participants with at least a 75% reduction from baseline in EASI (EASI75) at Week 12 |
| Change From Baseline in Dermatology Life Quality Index (DLQI) | Week 12 | Dermatology Life Quality Index Questionnaire (DLQI) is a simple 10-question validated questionnaire that has been used in more than 40 different skin conditions. The DLQI total score is defined as the sum of the 10 item scales, ranging from 0 to 30. The higher the value, the more severe the disease is. |
| Change From Baseline in Body Surface Area (BSA) | Week 12 | The overall body surface area (BSA) affected by atopic dermatitis is evaluated (from 0% to 100%). |
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) | Week 12 | The Patient-Oriented Eczema Measure (POEM) is a self-assessment of disease severity by the subject. The POEM has a maximum value of 28 based on the subject's response to seven questions scored from 0 to 4. The higher the value the more severe the disease is. |
Countries
Canada, Germany, United States
Participant flow
Recruitment details
First Patient Enrolled July 5, 2018 Last Patient Out August 14, 2019
Participants by arm
| Arm | Count |
|---|---|
| ASN002 40 mg 40 mg ASN002
ASN002: Daily dose of ASN002 for 12 weeks | 61 |
| ASN002 60 mg 60 mg ASN002
ASN002: Daily dose of ASN002 for 12 weeks | 59 |
| ASN002 80 mg 80 mg ASN002
ASN002: Daily dose of ASN002 for 12 weeks | 63 |
| Placebo Oral Tablet Matching placebo for ASN002 doses
Placebo Oral Tablet: Placebo of ASN002 for 12 weeks | 60 |
| Total | 243 |
Baseline characteristics
| Characteristic | ASN002 40 mg | ASN002 60 mg | ASN002 80 mg | Placebo Oral Tablet | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 9 Participants | 7 Participants | 4 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 50 Participants | 56 Participants | 56 Participants | 219 Participants |
| Age, Continuous | 40 years | 36 years | 39 years | 42 years | 40 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 11 Participants | 17 Participants | 13 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 46 Participants | 46 Participants | 47 Participants | 190 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Canada | 6 participants | 6 participants | 4 participants | 5 participants | 21 participants |
| Region of Enrollment Germany | 8 participants | 10 participants | 8 participants | 8 participants | 34 participants |
| Region of Enrollment United States | 47 participants | 43 participants | 51 participants | 47 participants | 188 participants |
| Sex: Female, Male Female | 34 Participants | 28 Participants | 32 Participants | 31 Participants | 125 Participants |
| Sex: Female, Male Male | 27 Participants | 31 Participants | 31 Participants | 29 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 59 | 0 / 63 | 0 / 60 |
| other Total, other adverse events | 20 / 61 | 19 / 59 | 24 / 63 | 9 / 60 |
| serious Total, serious adverse events | 4 / 61 | 0 / 59 | 2 / 63 | 0 / 60 |
Outcome results
Primary
Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12
The Eczema Area and Severity Index (EASI) is a composite score ranging from 0 to 72, the higher the value the worse the disease, that takes into account the degree of erythema, induration/infiltration (papules), excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the percentage of BSA involved for each body region and for the proportion of the body region to the whole body.
Time frame: Week 12
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | -15.8 score on a scale | Standard Deviation 10.88 |
| ASN002 60 mg | Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | -15.8 score on a scale | Standard Deviation 9.82 |
| ASN002 80 mg | Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | -17.5 score on a scale | Standard Deviation 11.6 |
| Placebo Oral Tablet | Change From Baseline in Eczema Area and Severity Index (EASI) at Week 12 | -13.1 score on a scale | Standard Deviation 11.87 |
Secondary
Change From Baseline in 5-D Pruritus (Itching) Scale
The 5-D Pruritus Scale is a 1-page, 5-question, validated questionnaire used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; subjects rated their symptoms over the preceding 2-week period as present or on a 1 to 5 scale, with 5 being the most affected. The total score of 5-D pruritus is a sum of the 5 scores to provide a total score range from 5 (best) to 25 (worst).
Time frame: Week 12
Population: mITT (MMRM model was used)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in 5-D Pruritus (Itching) Scale | -6.6 change in score on a scale | Standard Deviation 5.29 |
| ASN002 60 mg | Change From Baseline in 5-D Pruritus (Itching) Scale | -6.7 change in score on a scale | Standard Deviation 4.48 |
| ASN002 80 mg | Change From Baseline in 5-D Pruritus (Itching) Scale | -6.3 change in score on a scale | Standard Deviation 5.14 |
| Placebo Oral Tablet | Change From Baseline in 5-D Pruritus (Itching) Scale | -5.1 change in score on a scale | Standard Deviation 4.47 |
Secondary
Change From Baseline in Body Surface Area (BSA)
The overall body surface area (BSA) affected by atopic dermatitis is evaluated (from 0% to 100%).
Time frame: Week 12
Population: All patients with available data at Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Body Surface Area (BSA) | -57.2 percentage change from baseline | Standard Deviation 36.22 |
| ASN002 60 mg | Change From Baseline in Body Surface Area (BSA) | -51.1 percentage change from baseline | Standard Deviation 51.6 |
| ASN002 80 mg | Change From Baseline in Body Surface Area (BSA) | -50.1 percentage change from baseline | Standard Deviation 53.57 |
| Placebo Oral Tablet | Change From Baseline in Body Surface Area (BSA) | -38.1 percentage change from baseline | Standard Deviation 47.65 |
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI)
Dermatology Life Quality Index Questionnaire (DLQI) is a simple 10-question validated questionnaire that has been used in more than 40 different skin conditions. The DLQI total score is defined as the sum of the 10 item scales, ranging from 0 to 30. The higher the value, the more severe the disease is.
Time frame: Week 12
Population: All patients with available data at Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) | -8.1 score on a scale | Standard Deviation 8.28 |
| ASN002 60 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) | -5.9 score on a scale | Standard Deviation 6.59 |
| ASN002 80 mg | Change From Baseline in Dermatology Life Quality Index (DLQI) | -8.5 score on a scale | Standard Deviation 5.64 |
| Placebo Oral Tablet | Change From Baseline in Dermatology Life Quality Index (DLQI) | -5.5 score on a scale | Standard Deviation 6.48 |
Secondary
Change From Baseline in Patient-Oriented Eczema Measure (POEM)
The Patient-Oriented Eczema Measure (POEM) is a self-assessment of disease severity by the subject. The POEM has a maximum value of 28 based on the subject's response to seven questions scored from 0 to 4. The higher the value the more severe the disease is.
Time frame: Week 12
Population: Change from baseline at Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -8.9 score on a scale | Standard Deviation 8.37 |
| ASN002 60 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -8.5 score on a scale | Standard Deviation 8.1 |
| ASN002 80 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -9.1 score on a scale | Standard Deviation 7.91 |
| Placebo Oral Tablet | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -5.4 score on a scale | Standard Deviation 6.47 |
Secondary
Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1
The IGA is a global assessment of the current state of the disease. It is a 5-point (0-4) morphological assessment of overall disease severity. The 0 is the least severe and 4 is the most severe.
Time frame: Week 12
Population: All patients with evaluable data at Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASN002 40 mg | Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1 | 26.5 percentage of patients |
| ASN002 60 mg | Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1 | 29.8 percentage of patients |
| ASN002 80 mg | Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1 | 23.3 percentage of patients |
| Placebo Oral Tablet | Percentage of Participants With a Response of Investigator's Global Assessment (IGA) 0 or 1 | 19.0 percentage of patients |
Secondary
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD)
In the SCORAD grading system, six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) evaluate the Atopic Dermatitis severity. The overall body surface area affected by atopic dermatitis was evaluated (from 0% to 100%) and included in the SCORAD scores. Loss of sleep and pruritus were evaluated by subjects on a visual analog scale (0-10) and were based on the average of the last three days/nights. The sum of these measures represented the SCORAD, which could range from 0 to 103. The higher the score the more severe the disease.
Time frame: Week 12
Population: mITT (MMRM model was used to analyze the data)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | -45.0 percentage change from baseline | Standard Deviation 33.81 |
| ASN002 60 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | -47.3 percentage change from baseline | Standard Deviation 28.41 |
| ASN002 80 mg | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | -48.8 percentage change from baseline | Standard Deviation 28.02 |
| Placebo Oral Tablet | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) | -38.5 percentage change from baseline | Standard Deviation 31.66 |
Secondary
Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75)
Percent of participants with at least a 75% reduction from baseline in EASI (EASI75) at Week 12
Time frame: Week 12
Population: mITT (compared to PP all participants qualified for mITT were included but missing data were not imputed and not included in the percentages calculations)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ASN002 40 mg | Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75) | 49 percentage of patients |
| ASN002 60 mg | Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75) | 48.9 percentage of patients |
| ASN002 80 mg | Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75) | 48.8 percentage of patients |
| Placebo Oral Tablet | Percent of Participant With at Least a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI75) | 38.1 percentage of patients |