Atopic Dermatitis
Conditions
Keywords
ANB020, etokimab, eczema, moderate to severe
Brief summary
This study is designed to evaluate the efficacy, safety, and pharmacokinetic (PK) profiles of multiple doses of etokimab in adult participants with atopic dermatitis (AD).
Interventions
BIOLOGICALEtokimab
Humanized monoclonal antibody, administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
AnaptysBio, Inc.
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
1. Male or female participants must be 18 to 75 years of age, at the time of signing the informed consent. 2. Body mass index (BMI) of 18 to ≤ 35 kilogram per square meter (kg/m\^2) at screening. 3. Clinically confirmed diagnosis of AD. 4. Eczema Area and Severity Index (EASI) score ≥ 16, body surface area (BSA) involvement ≥ 10%, and an Investigator's Global Assessment (IGA) score (5-point scale) ≥ 3 at baseline. 5. Participants with a history of inadequate response to topical treatment, use of systemic treatments to treat AD, and/or for whom topical treatments are otherwise medically inadvisable. 6. Daily use of non-medicated emollient for at least 7 days prior to baseline.
Exclusion criteria
1. Treatment with topical corticosteroids, topical calcineurin inhibitors, or crisaborole within 2 weeks before dosing. 2. Prior exposure to an anti-interleukin (IL)-33 antibody. 3. Exposure to an investigational or licensed or other anti T-helper 2 (Th2) type cytokine or cytokine receptor antagonist within 16 weeks or 5 half-lives, whichever is longer. 4. History of prior exposure to any investigational or biologic systemic treatment within 5 half lives of the screening or is currently enrolled in another clinical study. 5. Have received systemic treatment for AD (including systemic corticosteroids, immunosuppressants or immunomodulating drugs, or phototherapy or use of a tanning booth) within 4 weeks before screening. 6. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | Baseline and Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | Baseline and Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). |
| Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | Baseline and Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). |
| Number of Participants Who Experienced an Adverse Event (AE) | From first dose to Week 24 | An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent adverse event (TEAE) is any AE that started or worsened in severity on or after the date and time of the study drug administration. A serious adverse event (SAE) is as any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect. |
| Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | Baseline and Week 16 | The vIGA-AD is a static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present 1. Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting 2. Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting 3. Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present 4. Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread in extent. Oozing or crusting may be present. Number of participants with ≥2 points reduction in vIGA-AD is presented. |
| Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | Baseline and Week 16 | EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease). |
| Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | Baseline and Week 16 | Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit. |
| Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | Baseline and Week 16 | Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit. |
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | Baseline and Week 16 | SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as extent of disease (0 \[no disease\]-102 \[worst disease\]). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 (none) to 18 (severe intensity). Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (itch: 0 \[no itch\] to 10 \[worst imaginable itch\] and sleeplessness: 0 \[no sleeplessness\] to 10 \[worst imaginable sleeplessness\]) (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 (no AD present) to 103.4 (worst). |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | Baseline and Week 16 | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A negative change from Baseline indicates improvement. |
| Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | Week 16 | vIGA-AD is static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present 1. Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting 2. Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting 3. Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present 4. Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread. Oozing or crusting may be present Participants who achieved vIGA-AD response of 0 (clear) or 1 (almost clear) are reported. |
Countries
Canada, Czechia, Germany, Poland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 75 centers in the United States, United Kingdom, Canada, Czech Republic, Germany, and Poland. The study enrolled adults with moderate to severe atopic dermatitis (AD). The study included a treatment period of 16 weeks (Week 0 to 16) followed by a safety follow-up for 8 weeks (Week 16 to Week 24).
Pre-assignment details
Participants were equally randomized on Day 1 to one of five treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo to etokimab, administered SC Q4W for up to 16 weeks. | 60 |
| Etokimab 20 mg SC Q4W Participants received etokimab 20 mg administered SC Q4W for up to 16 weeks. | 61 |
| Etokimab 300 mg / 150 mg SC Q8W Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC every 8 weeks (Q8W) for up to 16 weeks. At Weeks 4 and 12 participants received placebo. | 59 |
| Etokimab 300 mg / 150 mg SC Q4W Participants received a 300 mg loading dose of etokimab on Day 1 then 150 mg etokimab administered SC Q4W for up to 16 weeks. | 60 |
| Etokimab 600 mg / 300 mg SC Q4W Participants received a 600 mg loading dose of etokimab on Day 1 then 300 mg etokimab administered SC Q4W for up to 16 weeks. | 60 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 | 2 | 4 | 5 |
| Overall Study | Lost to Follow-up | 3 | 7 | 6 | 4 | 3 |
| Overall Study | Other | 0 | 2 | 1 | 0 | 3 |
| Overall Study | Physician Decision | 0 | 2 | 1 | 2 | 1 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Use of any excluded/prohibited medications | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 6 | 11 | 9 | 10 |
Baseline characteristics
| Characteristic | Placebo | Etokimab 20 mg SC Q4W | Etokimab 300 mg / 150 mg SC Q8W | Etokimab 300 mg / 150 mg SC Q4W | Etokimab 600 mg / 300 mg SC Q4W | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 15.92 | 40.1 years STANDARD_DEVIATION 16.76 | 39.7 years STANDARD_DEVIATION 14.38 | 38.9 years STANDARD_DEVIATION 14.61 | 37.1 years STANDARD_DEVIATION 14.78 | 39.0 years STANDARD_DEVIATION 15.28 |
| Eczema Area and Severity Index (EASI) | 26.6 units on a scale STANDARD_DEVIATION 11.45 | 29.8 units on a scale STANDARD_DEVIATION 12.08 | 27.1 units on a scale STANDARD_DEVIATION 10.38 | 32.2 units on a scale STANDARD_DEVIATION 13.06 | 29.5 units on a scale STANDARD_DEVIATION 12.19 | 29.1 units on a scale STANDARD_DEVIATION 11.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 11 Participants | 8 Participants | 8 Participants | 7 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 49 Participants | 51 Participants | 50 Participants | 53 Participants | 253 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 6 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 9 Participants | 10 Participants | 4 Participants | 6 Participants | 35 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 49 Participants | 48 Participants | 46 Participants | 55 Participants | 45 Participants | 243 Participants |
| Sex: Female, Male Female | 29 Participants | 25 Participants | 36 Participants | 24 Participants | 32 Participants | 146 Participants |
| Sex: Female, Male Male | 31 Participants | 36 Participants | 23 Participants | 36 Participants | 28 Participants | 154 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Grade 0 (Clear) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Grade 1 (Almost clear) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Grade 2 (Mild) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Grade 3 (Moderate) | 49 Participants | 36 Participants | 43 Participants | 43 Participants | 38 Participants | 209 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Grade 4 (Severe) | 10 Participants | 25 Participants | 16 Participants | 17 Participants | 22 Participants | 90 Participants |
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Missing | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 61 | 0 / 59 | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 24 / 60 | 22 / 61 | 23 / 59 | 18 / 60 | 26 / 60 |
| serious Total, serious adverse events | 1 / 60 | 2 / 61 | 3 / 59 | 3 / 60 | 3 / 60 |
Outcome results
Primary
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease).
Time frame: Baseline and Week 16
Population: Full Analysis Set. Missing data were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | -49.38 percent change | Standard Error 7.124 |
| Etokimab 20 mg SC Q4W | Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | -41.63 percent change | Standard Error 6.707 |
| Etokimab 300 mg / 150 mg SC Q8W | Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | -55.70 percent change | Standard Error 6.206 |
| Etokimab 300 mg / 150 mg SC Q4W | Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | -47.40 percent change | Standard Error 6.091 |
| Etokimab 600 mg / 300 mg SC Q4W | Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score | -44.56 percent change | Standard Error 7.811 |
p-value: 0.449895% CI: [-12.4066, 27.8983]ANCOVA
p-value: 0.50195% CI: [-24.774, 12.1262]ANCOVA
p-value: 0.834995% CI: [-16.6037, 20.5476]ANCOVA
p-value: 0.666295% CI: [-17.1892, 26.8275]ANCOVA
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 16
Population: Full Analysis Set with available data were analyzed. Missing data were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -5.61 units on a scale | Standard Error 0.946 |
| Etokimab 20 mg SC Q4W | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -5.35 units on a scale | Standard Error 0.966 |
| Etokimab 300 mg / 150 mg SC Q8W | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -6.52 units on a scale | Standard Error 0.945 |
| Etokimab 300 mg / 150 mg SC Q4W | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -6.05 units on a scale | Standard Error 0.945 |
| Etokimab 600 mg / 300 mg SC Q4W | Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 | -5.18 units on a scale | Standard Error 1.036 |
p-value: 0.755895% CI: [-2.3133, 3.1824]ANCOVA
p-value: 0.849795% CI: [-2.4081, 2.9218]ANCOVA
p-value: 0.501695% CI: [-3.5636, 1.7473]ANCOVA
p-value: 0.751195% CI: [-3.167, 2.287]ANCOVA
Secondary
Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16
The vIGA-AD is a static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present 1. Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting 2. Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting 3. Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present 4. Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread in extent. Oozing or crusting may be present. Number of participants with ≥2 points reduction in vIGA-AD is presented.
Time frame: Baseline and Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | 8 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | 7 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | 8 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | 10 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 2 Points From Baseline in the Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) at Week 16 | 9 Participants |
p-value: 0.605895% CI: [0.2481, 2.2543]Regression, Logistic
p-value: 0.952195% CI: [0.3356, 2.7923]Regression, Logistic
p-value: 0.690595% CI: [0.4457, 3.3878]Regression, Logistic
p-value: 0.939995% CI: [0.3671, 2.9518]Regression, Logistic
Secondary
Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16
Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit.
Time frame: Baseline and Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | 5 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | 6 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | 8 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | 9 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants Who Achieved a Reduction of ≥ 4 Points From Baseline in Weekly Averaged Peak Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | 9 Participants |
p-value: 0.8695% CI: [0.3175, 3.9513]Regression, Logistic
p-value: 0.322295% CI: [0.5511, 6.1214]Regression, Logistic
p-value: 0.256495% CI: [0.6089, 6.431]Regression, Logistic
p-value: 0.291295% CI: [0.5806, 6.1275]Regression, Logistic
Secondary
Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16
vIGA-AD is static 5-point scale to evaluate AD severity globally: 0: Clear - No inflammatory signs of AD (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Postinflammatory hyperpigmentation and/or hypopigmentation may be present 1. Almost clear - Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting 2. Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting 3. Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present 4. Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread. Oozing or crusting may be present Participants who achieved vIGA-AD response of 0 (clear) or 1 (almost clear) are reported.
Time frame: Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | 5 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | 5 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | 6 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | 8 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants Who Achieved a vIGA-AD Response of 0 (Clear) or 1 (Almost Clear) at Week 16 | 6 Participants |
p-value: 0.765995% CI: [0.329, 4.5268]Regression, Logistic
p-value: 0.627395% CI: [0.3895, 4.776]Regression, Logistic
p-value: 0.296795% CI: [0.5734, 6.1879]Regression, Logistic
p-value: 0.554495% CI: [0.4152, 5.1476]Regression, Logistic
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent adverse event (TEAE) is any AE that started or worsened in severity on or after the date and time of the study drug administration. A serious adverse event (SAE) is as any untoward medical occurrence that, at any dose: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent disability/incapacity; * Was a congenital anomaly/birth defect.
Time frame: From first dose to Week 24
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | Any TEAE | 38 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | Serious TEAE | 1 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Any TEAE | 40 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Serious TEAE | 2 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants Who Experienced an Adverse Event (AE) | Any TEAE | 41 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants Who Experienced an Adverse Event (AE) | Serious TEAE | 3 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Serious TEAE | 3 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Any TEAE | 42 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Any TEAE | 43 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants Who Experienced an Adverse Event (AE) | Serious TEAE | 3 Participants |
Secondary
Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16
EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease).
Time frame: Baseline and Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | 21 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | 19 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | 27 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | 21 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants With a 50% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 50 Response) at Week 16 | 18 Participants |
p-value: 0.799295% CI: [0.42, 1.9509]Regression, Logistic
p-value: 0.219795% CI: [0.757, 3.3572]Regression, Logistic
p-value: 0.719795% CI: [0.5345, 2.4774]Regression, Logistic
p-value: 0.677295% CI: [0.391, 1.8404]Regression, Logistic
Secondary
Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16
EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease).
Time frame: Baseline and Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | 10 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | 10 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | 14 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | 12 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants With a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75 Response) at Week 16 | 11 Participants |
p-value: 0.953795% CI: [0.3922, 2.6994]Regression, Logistic
p-value: 0.331695% CI: [0.6323, 3.8895]Regression, Logistic
p-value: 0.516695% CI: [0.5331, 3.4944]Regression, Logistic
p-value: 0.742695% CI: [0.4545, 3.0223]Regression, Logistic
Secondary
Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16
EASI measures the extent and severity of atopic eczema based on assessments of 4 body regions: head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected and the severity (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for symptoms such as redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) are assessed. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions. The EASI score ranges from 0 (no disease) to 72 (worse disease).
Time frame: Baseline and Week 16
Population: Full Analysis Set. Participants with missing data were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | 3 Participants |
| Etokimab 20 mg SC Q4W | Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | 5 Participants |
| Etokimab 300 mg / 150 mg SC Q8W | Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | 7 Participants |
| Etokimab 300 mg / 150 mg SC Q4W | Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | 7 Participants |
| Etokimab 600 mg / 300 mg SC Q4W | Number of Participants With a 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90 Response) at Week 16 | 2 Participants |
p-value: 0.454395% CI: [0.3998, 7.7615]Regression, Logistic
p-value: 0.187495% CI: [0.6314, 10.4827]Regression, Logistic
p-value: 0.172195% CI: [0.6506, 11.0814]Regression, Logistic
p-value: 0.675595% CI: [0.1086, 4.2141]Regression, Logistic
Secondary
Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16
Participants were asked to rate itch (pruritis) intensity at its worst (peak) during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch) in a daily electronic diary. Weekly average was calculated as the average of the 7 days before each visit.
Time frame: Baseline and Week 16
Population: Full Analysis Set with available data were analyzed. Missing data were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | -21.13 percent change | Standard Error 5.964 |
| Etokimab 20 mg SC Q4W | Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | -22.30 percent change | Standard Error 6.211 |
| Etokimab 300 mg / 150 mg SC Q8W | Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | -17.69 percent change | Standard Error 6.53 |
| Etokimab 300 mg / 150 mg SC Q4W | Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | -30.39 percent change | Standard Error 6.176 |
| Etokimab 600 mg / 300 mg SC Q4W | Percent Change From Baseline in Peak Weekly Averaged Numerical Rating Scale (NRS) for Pruritus Score at Week 16 | -27.18 percent change | Standard Error 6.192 |
p-value: 0.892795% CI: [-18.2117, 15.8686]ANCOVA
p-value: 0.703595% CI: [-14.2767, 21.1463]ANCOVA
p-value: 0.281995% CI: [-26.159, 7.6237]ANCOVA
p-value: 0.479395% CI: [-22.8452, 10.7333]ANCOVA
Secondary
Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as extent of disease (0 \[no disease\]-102 \[worst disease\]). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 (none) to 18 (severe intensity). Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (itch: 0 \[no itch\] to 10 \[worst imaginable itch\] and sleeplessness: 0 \[no sleeplessness\] to 10 \[worst imaginable sleeplessness\]) (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 (no AD present) to 103.4 (worst).
Time frame: Baseline and Week 16
Population: Full Analysis Set. Missing data were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -37.99 percent change | Standard Error 4.764 |
| Etokimab 20 mg SC Q4W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -31.42 percent change | Standard Error 4.605 |
| Etokimab 300 mg / 150 mg SC Q8W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -39.22 percent change | Standard Error 4.294 |
| Etokimab 300 mg / 150 mg SC Q4W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -35.48 percent change | Standard Error 4.401 |
| Etokimab 600 mg / 300 mg SC Q4W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -31.23 percent change | Standard Error 4.927 |
p-value: 0.326295% CI: [-6.5723, 19.7054]ANCOVA
p-value: 0.846595% CI: [-13.7439, 11.2782]ANCOVA
p-value: 0.694795% CI: [-10.0587, 15.082]ANCOVA
p-value: 0.328895% CI: [-6.8451, 20.3626]ANCOVA