Dermatitis, Atopic, Pruritus
Conditions
Keywords
Dermatitis, Atopic, Pruritus, Eczema, Itch
Brief summary
The goal of this clinical trial is to evaluate ASN008 in people with itch caused by eczema. The main questions it aims to answer are: * What is the efficacy and safety of ASN008? * What is the impact of ASN008 on itch in patients with atopic dermatitis? Participants will be asked to apply topical ASN008, or matching vehicle (placebo containing no active drug), to their eczema lesions twice daily for 4 weeks. Researchers will compare 3 different doses of ASN008 and a matching vehicle group to see which group responds best.
Detailed description
All participants will sign an informed consent form and undergo screening (within 28 days prior to Day 1). During the screening period, all treatments for Atopic Dermatitis (AD) (also known as eczema) and/or itch will be stopped to allow for wash out, as applicable and according to eligibility requirements. Consistent daily or twice daily use of a non-prescription emollient is required at least 7 days prior to Day 1 and throughout the trial until the follow-up (Week 8). No other products, including, but not limited to, topical corticosteroids, calcineurin inhibitors, biologics, or Janus Kinase (JAK) inhibitors (topical or oral) may be used during the trial. Eligible participants will be randomized in a 1:1:1:1 ratio to receive ASN008 gel 1.25 percent, ASN008 gel 2.5 percent, ASN008 gel 5.0 percent, or matching vehicle twice daily for 4 weeks (28 days), followed by a 4-week (28-day) follow-up period. The first dose of study treatment will be applied on Day 1 and the last dose will be applied on the morning of Day 28. Participants will be required to participate in 8 scheduled visits: Screening; Randomization (remote visit); Day 1; Week 1 (Day 8); Week 2 (Day 15); Week 3 (Day 22); Week 4 (Day 28); and Week 8 (Day 56)/early termination (ET). The trial duration per participant is up to 12 weeks (84 days): including up to 4 weeks (28 days) for the screening period, 4 weeks (28 days) for the treatment period, and up to 4 weeks (28 days) for the follow-up period. A participant is considered to have reached the end of the trial when they have completed their Day 56 (Week 8) or ET visit. The trial will be considered complete when the last participant has completed their last trial visit.
Interventions
DRUGASN008
ASN008 topical gel applied twice daily.
OTHERASN008 Matching Vehicle
The ASN008 matching vehicle formulation matches the formulation of each ASN008 topical gel dose, but contains no ASN008.
Sponsors
Formation Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
At all times, treatment and randomization information will be kept confidential and will not be released to the Sponsor's trial team until database lock is completed. Investigators, participants, and clinical staff will remain blinded throughout the trial.
Intervention model description
Eligible participants will be randomized to 1 of 4 cohorts: ASN008 gel 1.25 percent, 2.5 percent, 5 percent, or matching vehicle.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants, 18 years or older, at the time of informed consent. * Diagnosis of mild to moderate AD for at least 12 months with no significant disease flares for at least 4 weeks before Screening (based upon medical chart, treating physician, or participant report with documented clinical confirmation by the Investigator) * Validated Investigator Global Assessment (vIGA) score of 2 or 3 at Day 1. * Body surface area (BSA) affected by AD ≤20% at Day 1. * Peak Pruritus NRS ≥7 at Day 1. * Body mass index (BMI) ≤40 kg/m2 at Screening. * Willingness to avoid pregnancy or fathering children. * Participant is willing to participate for the duration of the trial, comply with all trial procedures, and is capable of giving informed consent.
Exclusion criteria
* Any female who is breastfeeding, pregnant, or who is planning to become pregnant during the trial. * Active infection requiring treatment, including skin infections (including clinically infected AD). * History of skin disease or presence of a skin condition that, in the opinion of the Investigator, would interfere with trial assessments. * Any clinically significant medical or psychiatric condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the Investigator, put the participant at undue risk or interfere with interpretation of trial results. * Use of any of the following treatments within the indicated washout period before Day 1: 1. Doxepin, hydroxyzine, or diphenhydramine use within 1 week prior to Day 1. 2. Use of topical product containing urea or any antihistamine within 1 week prior to Day 1. 3. Use of systemic antibiotic within 2 weeks, or topical antibiotics within 1 week, prior to Day 1. 4. Atopic dermatitis topical medication use within 2 weeks prior to Day 1, including, but not limited to, topical corticosteroids, crisaborole and any other topical phosphodiesterase-4 inhibitor, calcineurin inhibitors, JAK inhibitors, tars, bleach, antimicrobials, medical devices, and bleach or oatmeal baths. 5. Psoralen-UV-A or UV-B phototherapy (including tanning beds) or excimer laser within 4 weeks prior to Day 6. Systemic medication use including biologics that could affect AD less than 6 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, methotrexate, cyclosporine, hydroxycarbamide \[hydroxyurea\], azathioprine, oral/injectable corticosteroids), biologics and JAK inhibitors. * Known hypersensitivity to ASN008 or its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Peak Pruritus Numerical Rating Scale (NRS) | Baseline to Week 4 | Percent change of 7-day average daily peak pruritus NRS from Baseline to Week 4 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS | Baseline to Week 4 | Pruritus response defined as 7-day average of daily peak pruritus NRS reduction greater than or equal to 4 points from Baseline to Week 4 |
| Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline to Week 4 | This outcome measure evaluates the change and percent change in the Eczema Area and Severity Index (EASI) score from Baseline to Week 4. The EASI score measures the extent and severity of eczema across four body regions: head/neck, trunk, upper limbs, and lower limbs. Two components are assessed: severity of erythema, edema/papulation, excoriation, and lichenification (each scored 0 to 3, with 0 = none and 3 = severe) and the surface area affected (scored 0 to 6, with 0 = no involvement and 6 = 90%-100% involvement). Subscale scores are combined using weighted multipliers for each region (head/neck 0.1, upper limbs 0.2, trunk 0.3, lower limbs 0.4) to calculate the total score. The EASI is a composite score ranging from 0 (no eczema) to 72 (maximum severity and extent). Scores are summed to account for the severity of lesions and the percentage of body surface area (BSA) affected in each region. |
| Mean Change From Baseline in Total Body Surface Area (BSA) | Baseline to Week 4 | Change from Baseline in total BSA at week 4. |
| Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM) | Baseline to Week 4 | This outcome measure evaluates the change in the the Patient-Oriented Eczema Measure (POEM) score from Baseline to Week 4.The POEM is a self-assessment tool that evaluates eczema severity based on patient-reported symptoms over the previous week. It includes 7 questions addressing common symptoms: itch, sleep disturbance, bleeding, weeping, cracking, flaking, and dryness. Each question is scored on a scale from 0 to 4 based on frequency (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = every day). The scores are summed to generate a total score ranging from 0 to 28. Scores are interpreted as follows: 0-2 = clear or almost clear, 3-7 = mild eczema, 8-16 = moderate eczema, 17-24 = severe eczema, and 25-28 = very severe eczema. Higher scores indicate a greater symptom burden and worse disease severity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Inter- and Intra-subject Variability of ASN008 Pharmacokinetics (PK) Characterized by Peak Plasma Concentration (Cmax) | Baseline and Week 4 | ASN008 PK will be characterized using population-based methods to include Peak Plasma Concentration (Cmax). |
| Inter- and Intra-subject Variability of ASN008 Pharmacokinetics Characterized by Area Under the Plasma Concentration Versus Time Curve (AUC) | Baseline and Week 4 | ASN008 PK will be characterized using population-based methods to include area under the plasma concentration versus time curve (AUC) |
| Number of Treatment Emergent Adverse Events (TEAEs) | Baseline to Day 56 | Number of participants who experienced a TEAE. |
| Number of Investigational Product (IP)-Related TEAEs | Baseline to Day 56 | Number of participants who experienced an IP-related TEAE. |
| Incidence of TEAEs Leading to Treatment Discontinuation | Baseline to Day 56 | Incidence of TEAEs leading to treatment discontinuation from first dose through completion of follow-up period (up to a maximum of 56 days) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ASN008 1.25% ASN008 1.25% twice daily topical application applied as a thin layer (approximately 2 mg/cm\^2) for 4 weeks (28 days)
ASN008: ASN008 topical gel applied twice daily. | 34 |
| ASN008 2.5% ASN008 2.5% twice daily topical application applied as a thin layer (approximately 2 mg/cm\^2) for 4 weeks (28 days)
ASN008: ASN008 topical gel applied twice daily. | 32 |
| ASN008 5% ASN008 5% twice daily topical application applied as a thin layer (approximately 2 mg/cm\^2) for 4 weeks (28 days)
ASN008: ASN008 topical gel applied twice daily. | 32 |
| ASN008 Matching Vehicle ASN008 matching vehicle twice daily topical application applied as a thin layer (approximately 2 mg/cm\^2) for 4 weeks (28 days)
ASN008 Matching Vehicle: The ASN008 matching vehicle formulation matches the formulation of each ASN008 topical gel dose, but contains no ASN008. | 33 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomized | Did not receive study treatment | 2 | 4 | 4 | 3 |
| Treatment Period | Adverse Event | 1 | 1 | 1 | 1 |
| Treatment Period | Lost to Follow-up | 0 | 1 | 2 | 0 |
| Treatment Period | Protocol Violation | 0 | 0 | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | ASN008 Matching Vehicle | Total | ASN008 1.25% | ASN008 2.5% | ASN008 5% |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 14 Participants | 5 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 117 Participants | 29 Participants | 31 Participants | 29 Participants |
| Age, Continuous | 46.5 years STANDARD_DEVIATION 16.04 | 44.9 years STANDARD_DEVIATION 15.09 | 47.7 years STANDARD_DEVIATION 15.45 | 41.8 years STANDARD_DEVIATION 12.54 | 43.3 years STANDARD_DEVIATION 15.95 |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 11 Participants | 51 Participants | 14 Participants | 11 Participants | 15 Participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 22 Participants | 80 Participants | 20 Participants | 21 Participants | 17 Participants |
| Race/Ethnicity, Customized Race: Asian | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: Black or African American | 11 Participants | 37 Participants | 8 Participants | 11 Participants | 7 Participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race: Other | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race: White | 22 Participants | 89 Participants | 25 Participants | 19 Participants | 23 Participants |
| Sex/Gender, Customized Female | 23 Participants | 85 Participants | 20 Participants | 17 Participants | 25 Participants |
| Sex/Gender, Customized Male | 10 Participants | 46 Participants | 14 Participants | 15 Participants | 7 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 / 34 | 0 / 32 | 0 / 32 | 0 / 33 |
| other Total, other adverse events | 12 / 34 | 14 / 32 | 13 / 32 | 9 / 33 |
| serious Total, serious adverse events | 0 / 34 | 0 / 32 | 0 / 32 | 0 / 33 |
Outcome results
Primary
Daily Peak Pruritus Numerical Rating Scale (NRS)
Percent change of 7-day average daily peak pruritus NRS from Baseline to Week 4
Time frame: Baseline to Week 4
Population: Modified Intent to Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASN008 1.25% | Daily Peak Pruritus Numerical Rating Scale (NRS) | -45.6 percent change | Standard Error 5.04 |
| ASN008 2.5% | Daily Peak Pruritus Numerical Rating Scale (NRS) | -55.8 percent change | Standard Error 5.13 |
| ASN008 5% | Daily Peak Pruritus Numerical Rating Scale (NRS) | -48.3 percent change | Standard Error 5.2 |
| ASN008 Matching Vehicle | Daily Peak Pruritus Numerical Rating Scale (NRS) | -49.9 percent change | Standard Error 4.99 |
p-value: 0.5483Mixed Models Analysis
p-value: 0.4123Mixed Models Analysis
p-value: 0.8177Mixed Models Analysis
Secondary
Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score
This outcome measure evaluates the change and percent change in the Eczema Area and Severity Index (EASI) score from Baseline to Week 4. The EASI score measures the extent and severity of eczema across four body regions: head/neck, trunk, upper limbs, and lower limbs. Two components are assessed: severity of erythema, edema/papulation, excoriation, and lichenification (each scored 0 to 3, with 0 = none and 3 = severe) and the surface area affected (scored 0 to 6, with 0 = no involvement and 6 = 90%-100% involvement). Subscale scores are combined using weighted multipliers for each region (head/neck 0.1, upper limbs 0.2, trunk 0.3, lower limbs 0.4) to calculate the total score. The EASI is a composite score ranging from 0 (no eczema) to 72 (maximum severity and extent). Scores are summed to account for the severity of lesions and the percentage of body surface area (BSA) affected in each region.
Time frame: Baseline to Week 4
Population: Modified Intent to Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASN008 1.25% | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | -2.7 score on a scale | Standard Error 0.4 |
| ASN008 2.5% | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | -3.5 score on a scale | Standard Error 0.43 |
| ASN008 5% | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | -2.6 score on a scale | Standard Error 0.45 |
| ASN008 Matching Vehicle | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | -3.4 score on a scale | Standard Error 0.41 |
p-value: 0.2146Mixed Models Analysis
p-value: 0.8851Mixed Models Analysis
p-value: 0.1835Mixed Models Analysis
Secondary
Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM)
This outcome measure evaluates the change in the the Patient-Oriented Eczema Measure (POEM) score from Baseline to Week 4.The POEM is a self-assessment tool that evaluates eczema severity based on patient-reported symptoms over the previous week. It includes 7 questions addressing common symptoms: itch, sleep disturbance, bleeding, weeping, cracking, flaking, and dryness. Each question is scored on a scale from 0 to 4 based on frequency (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = every day). The scores are summed to generate a total score ranging from 0 to 28. Scores are interpreted as follows: 0-2 = clear or almost clear, 3-7 = mild eczema, 8-16 = moderate eczema, 17-24 = severe eczema, and 25-28 = very severe eczema. Higher scores indicate a greater symptom burden and worse disease severity.
Time frame: Baseline to Week 4
Population: Modified Intent to Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASN008 1.25% | Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM) | -5.0 score on a scale | Standard Error 1.04 |
| ASN008 2.5% | Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM) | -7.8 score on a scale | Standard Error 1.08 |
| ASN008 5% | Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM) | -6.3 score on a scale | Standard Error 1.11 |
| ASN008 Matching Vehicle | Mean Change From Baseline in the Patient-Oriented Eczema Measure (POEM) | -6.4 score on a scale | Standard Error 1.06 |
p-value: 0.3579Mixed Models Analysis
p-value: 0.3466Mixed Models Analysis
p-value: 0.9527Mixed Models Analysis
Secondary
Mean Change From Baseline in Total Body Surface Area (BSA)
Change from Baseline in total BSA at week 4.
Time frame: Baseline to Week 4
Population: Modified Intent to Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ASN008 1.25% | Mean Change From Baseline in Total Body Surface Area (BSA) | -2.6 Percentage | Standard Error 0.56 |
| ASN008 2.5% | Mean Change From Baseline in Total Body Surface Area (BSA) | -2.9 Percentage | Standard Error 0.59 |
| ASN008 5% | Mean Change From Baseline in Total Body Surface Area (BSA) | -1.5 Percentage | Standard Error 0.6 |
| ASN008 Matching Vehicle | Mean Change From Baseline in Total Body Surface Area (BSA) | -2.4 Percentage | Standard Error 0.56 |
p-value: 0.7982Mixed Models Analysis
p-value: 0.564Mixed Models Analysis
p-value: 0.2939Mixed Models Analysis
Secondary
Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS
Pruritus response defined as 7-day average of daily peak pruritus NRS reduction greater than or equal to 4 points from Baseline to Week 4
Time frame: Baseline to Week 4
Population: Modified Intent to Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASN008 1.25% | Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS | 12 Participants |
| ASN008 2.5% | Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS | 22 Participants |
| ASN008 5% | Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS | 15 Participants |
| ASN008 Matching Vehicle | Pruritus Response of ASN008 Topical Gel on Atopic Dermatitis (AD) Assessed by Daily Peak Pruritus NRS | 15 Participants |
p-value: 0.4601Fisher Exact
p-value: 0.0804Fisher Exact
p-value: >0.9999Fisher Exact
Other Pre-specified
Incidence of TEAEs Leading to Treatment Discontinuation
Incidence of TEAEs leading to treatment discontinuation from first dose through completion of follow-up period (up to a maximum of 56 days)
Time frame: Baseline to Day 56
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASN008 1.25% | Incidence of TEAEs Leading to Treatment Discontinuation | 1 Participants |
| ASN008 2.5% | Incidence of TEAEs Leading to Treatment Discontinuation | 1 Participants |
| ASN008 5% | Incidence of TEAEs Leading to Treatment Discontinuation | 1 Participants |
| ASN008 Matching Vehicle | Incidence of TEAEs Leading to Treatment Discontinuation | 1 Participants |
Other Pre-specified
Inter- and Intra-subject Variability of ASN008 Pharmacokinetics Characterized by Area Under the Plasma Concentration Versus Time Curve (AUC)
ASN008 PK will be characterized using population-based methods to include area under the plasma concentration versus time curve (AUC)
Time frame: Baseline and Week 4
Other Pre-specified
Inter- and Intra-subject Variability of ASN008 Pharmacokinetics (PK) Characterized by Peak Plasma Concentration (Cmax)
ASN008 PK will be characterized using population-based methods to include Peak Plasma Concentration (Cmax).
Time frame: Baseline and Week 4
Other Pre-specified
Number of Investigational Product (IP)-Related TEAEs
Number of participants who experienced an IP-related TEAE.
Time frame: Baseline to Day 56
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASN008 1.25% | Number of Investigational Product (IP)-Related TEAEs | 1 Participants |
| ASN008 2.5% | Number of Investigational Product (IP)-Related TEAEs | 3 Participants |
| ASN008 5% | Number of Investigational Product (IP)-Related TEAEs | 3 Participants |
| ASN008 Matching Vehicle | Number of Investigational Product (IP)-Related TEAEs | 1 Participants |
Other Pre-specified
Number of Treatment Emergent Adverse Events (TEAEs)
Number of participants who experienced a TEAE.
Time frame: Baseline to Day 56
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASN008 1.25% | Number of Treatment Emergent Adverse Events (TEAEs) | 12 Participants |
| ASN008 2.5% | Number of Treatment Emergent Adverse Events (TEAEs) | 14 Participants |
| ASN008 5% | Number of Treatment Emergent Adverse Events (TEAEs) | 11 Participants |
| ASN008 Matching Vehicle | Number of Treatment Emergent Adverse Events (TEAEs) | 8 Participants |