Atopic Dermatitis
Conditions
Keywords
AD, Dermatitis, Eczema
Brief summary
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous lirentelimab (AK002), given every 2 weeks for 7 doses, in adult subjects with moderate-to-severe AD inadequately controlled by topical treatments. Subjects who complete the randomized, double-blind, placebo-controlled treatment period may have the option to enroll in an open-label extension period and receive up to 7 doses of subcutaneous lirentelimab.
Interventions
DRUGAK002
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1)monoclonal antibody directed against Siglec-8
OTHERPlacebo
Placebo
Sponsors
Allakos 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 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subject is able to understand the information on the study, has the capacity to consent, and has provided written informed consent. 2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent form. 3. Chronic AD (as defined by the American Academy of Dermatology Consensus Criteria) (Eichenfield, 2014) that has been present for at least 3 years before the screening visit. 4. Documented recent history of inadequate response to treatment with topical medications such as topical corticosteroids, calcineurin inhibitors, JAK inhibitors, or PDE4 inhibitors (crisaborole) for at least 4 weeks in the 6 months prior to screening, or subjects for whom these topical treatments are otherwise medically inadvisable (e.g., because of side effects or safety risks). 5. Subjects who are biologic naive or biologic-exposed. Biologic-exposed includes patients who have demonstrated secondary loss of response, intolerance, or lack of continued access to biologics due to economic reasons. 6. EASI score of ≥16 at screening and at baseline. 7. Involvement of at least 10% or more of BSA at screening and at baseline. 8. An IGA score of 3 or above on a scale from 0-4 at screening and at baseline. 9. The subject should have applied a stable dose of non-medicated, non-prescription, topical emollient at least twice daily for 7 consecutive days immediately before the baseline visit. Key
Exclusion criteria
1. Current use of biologics for any indication. 2. Demonstrated lack of primary response to treatment with a biologic for the treatment of AD defined as no response to treatment despite complete adherence to the prescribed regimen for at least 3 months (primary non-responders). 3. Use of any of the following treatments within 4 weeks prior to the baseline visit or any condition that in the opinion of the Investigator is likely to require such treatment(s) during the first 4 weeks of study treatment: (i) phototherapy for AD; (ii) immunosuppressive or immunomodulatory drugs, including but not limited to systemic calcineurin inhibitors (e.g., cyclosporin, tacrolimus), mTOR inhibitors (e.g., sirolimus, everolimus), anti-metabolites (e.g., azathioprine, methotrexate, 6-mercaptopurine, leflunomide, mycophenolate mofetil), alkylating agents (e.g., cyclophosphamide), TNF inhibitors (e.g., infliximab, adalimumab), eosinophil depleting drugs (e.g., pramipexole), and systemic corticosteroids; (iii) oral JAK inhibitors within 8 weeks of the baseline visit. 4. Treatment with biologics: (i) any cell-depleting agents including but not limited to rituximab within 6 months prior to the baseline visit or until lymphocyte count returns to normal, whichever is longer; (ii) other biologics (e.g., dupilumab, omalizumab, etc) within 5 half-lives, if known, or 8 weeks prior to baseline visit, whichever is longer. 5. Use of any topical corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors (e.g., ruxolitinib), or topical PDE4 inhibitors (crisaborole) for the treatment of AD within 1 week prior to the baseline visit. 6. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit. 7. Treatment with chemotherapy or radiotherapy in the preceding 6 months. 8. Presence of skin comorbidities/concomitant conditions that may interfere with study assessments or interpretation of study results. 9. Planned or anticipated use of any prohibited medications. 10. History of malignancy except carcinoma in situ in the cervix, early-stage prostate cancer, or non-melanoma skin cancers. 11. Any disease, condition (medical or surgical), or cardiac abnormality that in the opinion of the Investigator would place the subject at increased risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Who Achieve 75% Improvement on the Eczema Area and Severity Index (EASI-75) at Week 14 | Baseline to Week 14 | The EASI score is a tool used to measure the extent (area) and severity of atopic dermatitis with respect to erythema, excoriation, induration, and lichenification over the 4 anatomic regions of the body: lower and upper extremities, trunk, and head. The total EASI score will be in a range from 0 to 72 points (from no disease to maximum disease severity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in EASI From Baseline to Week 14 | Baseline to Week 14 | The EASI score is a tool used to measure the extent (area) and severity of atopic dermatitis with respect to erythema, excoriation, induration, and lichenification over the 4 anatomic regions of the body: lower and upper extremities, trunk, and head. The total EASI score will be in a range from 0 to 72 points (from no disease to maximum disease severity). |
| Proportion of Subjects Achieving an IGA Score of 0 or 1 and a 2-point Improvement at Week 14 vs Baseline | Baseline to Week 14 | The Investigator's Global Assessment (IGA) is a 5-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4 and assesses disease severity and clinical response using a 5-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 4 = severe. The score is determined by ranking the extent of erythema and papulation/infiltration. A decrease in score relates to an improvement in signs and symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Through study completion, up to 38 weeks (open-label extension period) | Adverse events were assessed throughout the open-label extension period. |
Countries
Germany, United States
Participant flow
Recruitment details
130 subjects who were enrolled in the main study received up to 7 doses of AK002 or placebo. 112 subjects from the main study continued into the open-label extension (OLE) period and received up to 7 doses of AK002.
Participants by arm
| Arm | Count |
|---|---|
| AK002 SC 300 mg (Main Study) Subjects in this arm received up to 7 doses of 300 mg of lirentelimab (AK002) administered subcutaneously every 2 weeks.
AK002: Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1)monoclonal antibody directed against Siglec-8 | 65 |
| Placebo (Main Study) Subjects in this arm received up to 7 doses of placebo administered subcutaneously every 2 weeks.
Placebo: Placebo | 65 |
| Total | 130 |
Baseline characteristics
| Characteristic | Placebo (Main Study) | Total | AK002 SC 300 mg (Main Study) |
|---|---|---|---|
| Age, Continuous | 35 years | 38 years | 41 years |
| Eczema Area and Severity Index (EASI) Score | 30.1 Score on a scale STANDARD_DEVIATION 10.7 | 29.1 Score on a scale STANDARD_DEVIATION 9.2 | 28.1 Score on a scale STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 44 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 80 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Investigator's Global Assessment (IGA) Score | 3 Score on a scale STANDARD_DEVIATION 1 | 3 Score on a scale STANDARD_DEVIATION 1 | 3 Score on a scale STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 38 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 35 Participants | 78 Participants | 43 Participants |
| Region of Enrollment Germany | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment United States | 53 Participants | 106 Participants | 53 Participants |
| Sex: Female, Male Female | 36 Participants | 71 Participants | 35 Participants |
| Sex: Female, Male Male | 29 Participants | 59 Participants | 30 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 / 65 | 0 / 65 | 0 / 55 | 0 / 57 |
| other Total, other adverse events | 27 / 65 | 25 / 65 | 15 / 55 | 20 / 57 |
| serious Total, serious adverse events | 1 / 65 | 3 / 65 | 2 / 55 | 0 / 57 |
Outcome results
Primary
The Proportion of Subjects Who Achieve 75% Improvement on the Eczema Area and Severity Index (EASI-75) at Week 14
The EASI score is a tool used to measure the extent (area) and severity of atopic dermatitis with respect to erythema, excoriation, induration, and lichenification over the 4 anatomic regions of the body: lower and upper extremities, trunk, and head. The total EASI score will be in a range from 0 to 72 points (from no disease to maximum disease severity).
Time frame: Baseline to Week 14
Population: Modified Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AK002 SC 300 mg (Main Study) | The Proportion of Subjects Who Achieve 75% Improvement on the Eczema Area and Severity Index (EASI-75) at Week 14 | 23.0 percentage of participants |
| Placebo (Main Study) | The Proportion of Subjects Who Achieve 75% Improvement on the Eczema Area and Severity Index (EASI-75) at Week 14 | 18.0 percentage of participants |
p-value: 0.466295% CI: [-9.8, 19.8]Cochran-Mantel-Haenszel
Secondary
Percent Change in EASI From Baseline to Week 14
The EASI score is a tool used to measure the extent (area) and severity of atopic dermatitis with respect to erythema, excoriation, induration, and lichenification over the 4 anatomic regions of the body: lower and upper extremities, trunk, and head. The total EASI score will be in a range from 0 to 72 points (from no disease to maximum disease severity).
Time frame: Baseline to Week 14
Population: Modified Intent-to-Treat Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AK002 SC 300 mg (Main Study) | Percent Change in EASI From Baseline to Week 14 | -36.0 Percentage of change | Standard Error 8.7 |
| Placebo (Main Study) | Percent Change in EASI From Baseline to Week 14 | -26.3 Percentage of change | Standard Error 8.7 |
p-value: 0.396895% CI: [-32.2, 12.9]Mixed Models Analysis
Secondary
Proportion of Subjects Achieving an IGA Score of 0 or 1 and a 2-point Improvement at Week 14 vs Baseline
The Investigator's Global Assessment (IGA) is a 5-point scale that provides a global clinical assessment of AD severity ranging from 0 to 4 and assesses disease severity and clinical response using a 5-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 4 = severe. The score is determined by ranking the extent of erythema and papulation/infiltration. A decrease in score relates to an improvement in signs and symptoms.
Time frame: Baseline to Week 14
Population: Modified Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AK002 SC 300 mg (Main Study) | Proportion of Subjects Achieving an IGA Score of 0 or 1 and a 2-point Improvement at Week 14 vs Baseline | 11.5 percentage of participants |
| Placebo (Main Study) | Proportion of Subjects Achieving an IGA Score of 0 or 1 and a 2-point Improvement at Week 14 vs Baseline | 8.2 percentage of participants |
p-value: 0.762595% CI: [-15.2, 21.6]Fisher Exact
Other Pre-specified
Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period
Adverse events were assessed throughout the open-label extension period.
Time frame: Through study completion, up to 38 weeks (open-label extension period)
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AK002 SC 300 mg (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 treatment-related adverse events | 3 Participants |
| AK002 SC 300 mg (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 serious adverse events | 2 Participants |
| AK002 SC 300 mg (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with an adverse event leading to study drug discontinuation | 2 Participants |
| AK002 SC 300 mg (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 treatment-related serious adverse events | 0 Participants |
| AK002 SC 300 mg (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 adverse events | 30 Participants |
| Placebo (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 treatment-related serious adverse events | 0 Participants |
| Placebo (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 adverse events | 31 Participants |
| Placebo (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 treatment-related adverse events | 13 Participants |
| Placebo (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with an adverse event leading to study drug discontinuation | 1 Participants |
| Placebo (Main Study) | Safety and Tolerability of up to 7 Doses of Open-label AK002 in Subjects With Atopic Dermatitis in the Open-label Extension Period | Subjects with ≥1 serious adverse events | 0 Participants |