Atopic Dermatitis
Conditions
Keywords
eczema
Brief summary
This is a randomized open label study to evaluate the long term safety of ASN002 in subjects with moderate to severe atopic dermatitis (AD).
Detailed description
This is a randomized open label study where subjects with moderate to severe atopic dermatitis will roll over from the Phase 1 ASN002AD-101 (NCT03139981) and ASN002AD-201 (NCT03531957) Ph2b study and be randomized to receive ASN002 at 40mg, 60mg, or 80mg once daily for up to 24 months. This study will also characterize the pharmacokinetics of ASN002 through blood sampling from subjects who consent.
Interventions
DRUGASN002
Daily dose of ASN002 for up to 110 weeks
Sponsors
Asana BioSciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject with a history of moderate to severe atopic dermatitis who participated in the preceding ASN002AD-201 and ASN002AD-101 study * Subject must be a candidate for prolonged open label ASN002/gusacitinib treatment according to the investigator's judgment. * Subject has been using an emollient daily for at least 1 week prior to Day 1 and agrees to continue using that same emollient daily throughout the study. * Men and women participating in the study must use medically acceptable birth control or total abstinence from sexual intercourse * Subject is willing to participate and is capable of giving informed consent. Note: Consent must be obtained prior to any study-related procedures. * Subjects must be willing to comply with all study procedures and must be available for the duration of the study. * Subject has a body mass index (BMI) ≤ 38 kg/m2.
Exclusion criteria
* Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study. * Subject has clinically infected atopic dermatitis. * 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 * Subject has a history of skin disease or presence of skin condition that, in the opinion of the investigator, would interfere with the study assessments. * Subject has a history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past. * Willing to comply with discontinuation of certain treatments for AD, as directed by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area Severity Index (EASI) Score | 3 Months | 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. Due to early termination of the study, all efficacy analyses were descriptive in nature |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (1) | 3 months | 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 IGA is selected using descriptors that best describe the overall appearance of the lesions at any given point. Signs like inflammation, redness, oozing, and crusting are evaluated. The 0 is the least severe and 4 is the most severe. Due to early termination of the study, all efficacy analyses were descriptive in nature. |
| Change From Baseline in 5-D Pruritus (Itch) Scale | 3 months | The 5-D Pruritus Scale is a validated questionnaire used in clinical trials to assess the degree, duration, direction, disability, and distribution of the itch to rate the their symptoms over the preceding 2-week period. Each symptoms is scored on a scale of 1 to 5, 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). Due to early termination of the study, all efficacy analyses were descriptive in nature |
| Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS) | 3 months | Intensity of itch will be measured using an NRS to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where 0 represents no itching and 10 represents worst itching imaginable Due to early termination of the study, all efficacy analyses were descriptive in nature |
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) | 3 months | POEM developed by Charman et al. is a self-assessment of disease severity by the participant. The POEM includes 7 questions to evaluate the number of days the signs and symptoms of eczema over the last week. The answer to each question is categorized by the frequency of the sign or symptom from no days to 7 days. Each question is scored from 0 to 4 and the sum of the questions if the POEM score. The score ranges from 0 to 28 with 0 being the least frequency and 28 showing that all the signs and symptoms occur every day. Therefore, the higher the score, the more severe the eczema. Due to early termination of the study, all efficacy analyses were descriptive in nature |
Countries
Canada, United States
Participant flow
Recruitment details
Participants from ASN002AD-101 and ASN002AD-201 were eligible to enter the OLE study if they (1) had participated in ASN002AD-101 study OR (2) had participated in ASN002AD 201 study, had completed at least the first 4 weeks without the use of prohibited treatments for AD, and had completed the study visits up to Week 12. Participants who had received the placebo in the other preceding studies were allowed to be enrolled in the OLE study except those who were responders at Week 12 based on EASI75
Pre-assignment details
Those participants that received placebo in ASN002AD-201 or were enrolled in ASN002-101 were allocated as starting treatment, and those that received ASN002 in ASN002AD-201 trial are allocated as continuing treatment.
Participants by arm
| Arm | Count |
|---|---|
| ASN002 40 mg ASN002 40 mg
ASN002: Daily dose of ASN002 for up to 110 weeks | 45 |
| ASN002 60 mg ASN002 60 mg
ASN002: Daily dose of ASN002 for up to 110 weeks | 41 |
| ASN002 80 mg ASN002 80 mg
ASN002: Daily dose of ASN002 for up to 110 weeks | 76 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 4 |
| Overall Study | Early Termination of study due to COVID-19 | 42 | 33 | 56 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 | 7 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 8 |
Baseline characteristics
| Characteristic | ASN002 80 mg | Total | ASN002 40 mg | ASN002 60 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 19 Participants | 6 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 69 Participants | 143 Participants | 39 Participants | 35 Participants |
| Age, Continuous | 42.9 years STANDARD_DEVIATION 15.9 | 42.4 years STANDARD_DEVIATION 16.82 | 41.8 years STANDARD_DEVIATION 18.34 | 42.3 years STANDARD_DEVIATION 17.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 12 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 26 Participants | 8 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 120 Participants | 32 Participants | 31 Participants |
| Sex: Female, Male Female | 36 Participants | 84 Participants | 26 Participants | 22 Participants |
| Sex: Female, Male Male | 40 Participants | 78 Participants | 19 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 41 | 0 / 76 |
| other Total, other adverse events | 2 / 45 | 3 / 41 | 6 / 76 |
| serious Total, serious adverse events | 0 / 45 | 0 / 41 | 1 / 76 |
Outcome results
Primary
Change From Baseline in Eczema Area Severity Index (EASI) Score
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. Due to early termination of the study, all efficacy analyses were descriptive in nature
Time frame: 3 Months
Population: The number of participants analyzed includes those that had a 3 months time point assessed before early termination of the study. Therefore, the numbers analyzed are not the same as those that started or completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Eczema Area Severity Index (EASI) Score | -22.88 Change in score on a scale | Standard Deviation 12.914 |
| ASN002 60 mg | Change From Baseline in Eczema Area Severity Index (EASI) Score | -18.07 Change in score on a scale | Standard Deviation 7.687 |
| ASN002 80 mg | Change From Baseline in Eczema Area Severity Index (EASI) Score | -17.38 Change in score on a scale | Standard Deviation 13.561 |
Secondary
Change From Baseline in 5-D Pruritus (Itch) Scale
The 5-D Pruritus Scale is a validated questionnaire used in clinical trials to assess the degree, duration, direction, disability, and distribution of the itch to rate the their symptoms over the preceding 2-week period. Each symptoms is scored on a scale of 1 to 5, 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). Due to early termination of the study, all efficacy analyses were descriptive in nature
Time frame: 3 months
Population: The number of participants analyzed includes those that had a 3 months time point assessed before early termination of the study. Therefore, the numbers analyzed are not the same as those that started or completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in 5-D Pruritus (Itch) Scale | -7.7 change in score on a scale | Standard Deviation 4.21 |
| ASN002 60 mg | Change From Baseline in 5-D Pruritus (Itch) Scale | -7.1 change in score on a scale | Standard Deviation 4.93 |
| ASN002 80 mg | Change From Baseline in 5-D Pruritus (Itch) Scale | -6.9 change in score on a scale | Standard Deviation 4.97 |
Secondary
Change From Baseline in Patient-Oriented Eczema Measure (POEM)
POEM developed by Charman et al. is a self-assessment of disease severity by the participant. The POEM includes 7 questions to evaluate the number of days the signs and symptoms of eczema over the last week. The answer to each question is categorized by the frequency of the sign or symptom from no days to 7 days. Each question is scored from 0 to 4 and the sum of the questions if the POEM score. The score ranges from 0 to 28 with 0 being the least frequency and 28 showing that all the signs and symptoms occur every day. Therefore, the higher the score, the more severe the eczema. Due to early termination of the study, all efficacy analyses were descriptive in nature
Time frame: 3 months
Population: The number of participants analyzed includes those that had a 3 months time point assessed before early termination of the study. Therefore, the numbers analyzed are not the same as those that started or completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -11.0 change in score on a scale | Standard Deviation 7.04 |
| ASN002 60 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -11.5 change in score on a scale | Standard Deviation 8.73 |
| ASN002 80 mg | Change From Baseline in Patient-Oriented Eczema Measure (POEM) | -8.7 change in score on a scale | Standard Deviation 8.08 |
Secondary
Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS)
Intensity of itch will be measured using an NRS to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where 0 represents no itching and 10 represents worst itching imaginable Due to early termination of the study, all efficacy analyses were descriptive in nature
Time frame: 3 months
Population: The number of participants analyzed includes those that had a 3 months time point assessed before early termination of the study. Therefore, the numbers analyzed are not the same as those that started or completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ASN002 40 mg | Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS) | -3.4 change in score on a scale | Standard Deviation 2.99 |
| ASN002 60 mg | Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS) | -3.3 change in score on a scale | Standard Deviation 2.93 |
| ASN002 80 mg | Change From Baseline in Pruritus (Itch) Numeric Rating Scale (NRS) | -3.2 change in score on a scale | Standard Deviation 3.16 |
Secondary
Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (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 IGA is selected using descriptors that best describe the overall appearance of the lesions at any given point. Signs like inflammation, redness, oozing, and crusting are evaluated. The 0 is the least severe and 4 is the most severe. Due to early termination of the study, all efficacy analyses were descriptive in nature.
Time frame: 3 months
Population: The number of participants analyzed includes those that had a 3 months time point assessed before early termination of the study. Therefore, the numbers analyzed are not the same as those that started or completed the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASN002 40 mg | Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (1) | 8 Participants |
| ASN002 60 mg | Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (1) | 8 Participants |
| ASN002 80 mg | Number of Participants Achieving an Investigator Global Assessment (IGA) Scale of Clear (0) or Almost Clear (1) | 9 Participants |