Atopic Dermatitis
Conditions
Brief summary
This study will assess the efficacy and safety of MSTT1041A (astegolimab) in participants with moderate to severe atopic dermatitis (AD). The study consists of a screening period, a 16-week treatment period, and an 8-week follow-up period.
Interventions
DRUGMSTT1041A
Participants will receive subcutaneous (SC) MSTT1041A
DRUGPlacebo
Participants will receive SC placebo
Sponsors
Genentech, 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
* Ability to comply with the study protocol * Chronic AD that has been present for at least 3 years before the screening visit * Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications (medications or treatments applied directly to part of the body) or for whom topical treatments are otherwise medically inadvisable
Exclusion criteria
* Prior treatment with MSTT1041A * Treatment with any investigational therapy (with the exception of biologics) within 8 weeks or within 5 half-lives whichever is longer, before screening * Treatment with any cell-depleting agents within 6 months before screening, or until lymphocyte count returns to normal, whichever is longer * Treatment with other biologics within 3 months or 5 half-lives before screening, whichever is longer * Comorbid conditions that may interfere with evaluation of investigational medicinal product * History or evidence of substance abuse that would pose a risk to participant safety, interfere with the conduct of the study, have an impact on the study results, or affect the participant's ability to participate in the study * History of anaphylaxis, hypersensitivity to a biologic agent, or known hypersensitivity to any component of the MSTT1041A or placebo injection * Planned surgical intervention during the course of the study * Pregnant or breastfeeding, or intending to become pregnant during the study * Participant who is a member of the investigational team or his/her immediate family
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Total Eczema Area and Severity Index (EASI) Score | Baseline, Week 16 | The Eczema Area and Severity Index (EASI) is a standardized instrument to evaluate the extent and severity of atopic dermatitis. An area score comprised of the percentage of skin affected by eczema for each of 4 body regions (head/neck, trunk, upper extremities, and lower extremities) is calculated with 0 = none, 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89%, and 6 = 90-100%. Severity is scored for each of the 4 body regions by the summation of the intensity scores for 4 signs (redness, thickness, scratching, and lichenification), with 0 = none/absent, 1 = mild, 2 = moderate, and 3 = severe. The minimum final EASI score is 0 and the maximum score is 72. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieve >/=75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) Score | Baseline, Week 16 | — |
| Percent Change in Pruritus as Assessed by a Numeric Rating Scale (NRS) | Baseline, Week 16 | The Peak Pruritis Numerical Rating Scale (NRS) is a single-item patient-reported outcome (PRO) of itch severity rated on a scale of 0-10, with 0 = no itch and 10 = worst itch imaginable for the prior 24-hour period. |
| Percent Change in Body Surface Area (BSA) With Atopic Dermatitis (AD) Involvement | Baseline, Week 16 | — |
| Proportion of Participants Who Achieve Investigator's Global Assessment (IGA) Response of 0 or 1 | Baseline, Week 16 | — |
| Percentage of Participants With Adverse Events (AE) | Up to Week 24 | — |
| Serum Concentrations of MSTT1041A | At pre-defined intervals from baseline up to Week 24 | — |
| Incidence of Treatment-Emergent Anti-Drug Antibodies (ADAs) | Up to Week 24 | — |
| Percent Change in Disease Severity as Assessed by SCORing Atopic Dermatitis (SCORAD) | Baseline, Week 16 | SCORAD is a tool used to assess the extent and severity of eczema based on three aspects of disease severity: extent, intensity, and a subjective (PRO) symptoms. A total score (0-103) is calculated, with higher scores indicating a higher extent and severity of symptoms. |
Countries
Germany, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a loading dose of SC placebo matched to MSTT1041A followed by SC placebo Q4W. | 32 |
| Treatment Participants received a loading dose of 245 mg of subcutaneous (SC) MSTT1041A, followed by 490 mg of SC MSTT1041A every 4 weeks (Q4W). | 33 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Placebo | Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 31 Participants | 61 Participants |
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 14.4 | 39.7 Years STANDARD_DEVIATION 15.2 | 39.5 Years STANDARD_DEVIATION 14.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 30 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 25 Participants | 45 Participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 34 |
| other Total, other adverse events | 8 / 31 | 3 / 34 |
| serious Total, serious adverse events | 0 / 31 | 1 / 34 |
Outcome results
Primary
Percent Change of Total Eczema Area and Severity Index (EASI) Score
The Eczema Area and Severity Index (EASI) is a standardized instrument to evaluate the extent and severity of atopic dermatitis. An area score comprised of the percentage of skin affected by eczema for each of 4 body regions (head/neck, trunk, upper extremities, and lower extremities) is calculated with 0 = none, 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89%, and 6 = 90-100%. Severity is scored for each of the 4 body regions by the summation of the intensity scores for 4 signs (redness, thickness, scratching, and lichenification), with 0 = none/absent, 1 = mild, 2 = moderate, and 3 = severe. The minimum final EASI score is 0 and the maximum score is 72.
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Percent Change of Total Eczema Area and Severity Index (EASI) Score | -51.47 Percentage | Standard Error 8.639 |
| Placebo | Percent Change of Total Eczema Area and Severity Index (EASI) Score | -58.24 Percentage | Standard Error 9.092 |
Secondary
Incidence of Treatment-Emergent Anti-Drug Antibodies (ADAs)
Time frame: Up to Week 24
Population: Safety population - all randomized participants who received at least one dose of study drug. Participants are grouped according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Incidence of Treatment-Emergent Anti-Drug Antibodies (ADAs) | 1 Participants |
| Placebo | Incidence of Treatment-Emergent Anti-Drug Antibodies (ADAs) | 0 Participants |
Secondary
Percentage of Participants With Adverse Events (AE)
Time frame: Up to Week 24
Population: Safety population - all randomized participants who received at least one dose of study drug. Participants are grouped according to actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Percentage of Participants With Adverse Events (AE) | 14 Participants |
| Placebo | Percentage of Participants With Adverse Events (AE) | 18 Participants |
Secondary
Percent Change in Body Surface Area (BSA) With Atopic Dermatitis (AD) Involvement
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Percent Change in Body Surface Area (BSA) With Atopic Dermatitis (AD) Involvement | -42.23 Percentage | Standard Error 8.637 |
| Placebo | Percent Change in Body Surface Area (BSA) With Atopic Dermatitis (AD) Involvement | -38.87 Percentage | Standard Error 9.134 |
Secondary
Percent Change in Disease Severity as Assessed by SCORing Atopic Dermatitis (SCORAD)
SCORAD is a tool used to assess the extent and severity of eczema based on three aspects of disease severity: extent, intensity, and a subjective (PRO) symptoms. A total score (0-103) is calculated, with higher scores indicating a higher extent and severity of symptoms.
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Percent Change in Disease Severity as Assessed by SCORing Atopic Dermatitis (SCORAD) | -35.45 Percentage | Standard Error 6.837 |
| Placebo | Percent Change in Disease Severity as Assessed by SCORing Atopic Dermatitis (SCORAD) | -39.50 Percentage | Standard Error 7.202 |
Secondary
Percent Change in Pruritus as Assessed by a Numeric Rating Scale (NRS)
The Peak Pruritis Numerical Rating Scale (NRS) is a single-item patient-reported outcome (PRO) of itch severity rated on a scale of 0-10, with 0 = no itch and 10 = worst itch imaginable for the prior 24-hour period.
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Percent Change in Pruritus as Assessed by a Numeric Rating Scale (NRS) | -31.22 Percentage | Standard Error 7.376 |
| Placebo | Percent Change in Pruritus as Assessed by a Numeric Rating Scale (NRS) | -39.43 Percentage | Standard Error 7.839 |
Secondary
Proportion of Participants Who Achieve >/=75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) Score
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Proportion of Participants Who Achieve >/=75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) Score | 27.3 Percentage |
| Placebo | Proportion of Participants Who Achieve >/=75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) Score | 18.8 Percentage |
Secondary
Proportion of Participants Who Achieve Investigator's Global Assessment (IGA) Response of 0 or 1
Time frame: Baseline, Week 16
Population: ITT population - all participants randomized on Day 1, grouped by the treatment assigned at randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Proportion of Participants Who Achieve Investigator's Global Assessment (IGA) Response of 0 or 1 | 15.2 Percentage |
| Placebo | Proportion of Participants Who Achieve Investigator's Global Assessment (IGA) Response of 0 or 1 | 6.3 Percentage |
Secondary
Serum Concentrations of MSTT1041A
Time frame: At pre-defined intervals from baseline up to Week 24
Population: PK population: The PK population included participants from the safety population with at least one available post-study treatment PK sample.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Serum Concentrations of MSTT1041A | Day 1 Visit 2/prior to infusion | NA ug/mL | — |
| Treatment | Serum Concentrations of MSTT1041A | Week 1 Visit 3/prior to infusion | 42.6 ug/mL | Geometric Coefficient of Variation 34.4 |
| Treatment | Serum Concentrations of MSTT1041A | Week 4 Visit 5/prior to infusion | 37.6 ug/mL | Geometric Coefficient of Variation 52.5 |
| Treatment | Serum Concentrations of MSTT1041A | Week 8 Visit 7/prior to infusion | 36.6 ug/mL | Geometric Coefficient of Variation 54.5 |
| Treatment | Serum Concentrations of MSTT1041A | Week 12 Visit 9/prior to infusion | 40.1 ug/mL | Geometric Coefficient of Variation 60.5 |
| Treatment | Serum Concentrations of MSTT1041A | Week 16 Visit 11 | 38.2 ug/mL | Geometric Coefficient of Variation 76 |
| Treatment | Serum Concentrations of MSTT1041A | Subject disposition - period completion/early discontinuation | 7.83 ug/mL | Geometric Coefficient of Variation 151.2 |