Atopic Dermatitis
Conditions
Keywords
Lutikizumab, ABT-981
Brief summary
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. The purpose of this study is to evaluate the clinical efficacy and safety of single therapies and/or combination therapies for moderate to severe AD through multiple substudies. This study will consist of multiple sub-studies, Sub-Study 1 will have a randomized, placebo controlled period 1 followed by a lutikizumab treatment period 2 enrolling 80 participants at a 1 to 1 ratio. In Sub-Study 1, participants will receive subcutaneous (SC) injections of lutikizumab or matching placebo every other week for 16 weeks followed by an additional 32 weeks of subcutaneous (SC) injections of lutikizumab every other week for a total of 52 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and biomarker collections.
Interventions
DRUGLutikizumab
Subcutaneous (SC) Injection
DRUGPlacebo
Subcutaneous (SC) Injection
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AD with onset of symptoms at least 1 year prior to the Baseline Visit and participant meets Hanifin and Rajka criteria. * Participant has applied non-medicated, additive-free bland emollient twice daily for at least 7 days before the Baseline Visit. * History of inadequate response to topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), or topical JAK inhibitors, OR systemic treatment for AD, OR participants for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
Exclusion criteria
* Use of the following AD treatments within the specified washout period prior to the Baseline Visit: \-- Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4) inhibitors, IFN-γ, and mycophenolate mofetil within 5 half-lives \[if known\] or within 4 weeks, whichever is longer; \-- Any biologic treatments, (within 5 half-lives \[if known\]) or within 12 weeks (whichever is longer), or as specified below: \< 8 weeks for dupilumab; \< 12 weeks for nemolizumab; \< 16 weeks for tralokinumab and lebrikizumab. * Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks. * Herbal treatments (e.g., traditional Chinese medicines) within 4 weeks. * Topical treatments (with the exception of non-medicated, additive-free bland emollients), including but not limited to TCS, TCIs, or topical PDE-4 inhibitors within 7 days. * Topical JAK inhibitor within 14 days. * Systemic JAK inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, upadacitinib, abrocitinib \[PF-04965842\], and filgotinib) within 5 half-lives \[if known\] or within 14 days, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16 | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. |
| Percentage of Participants Who Reported Adverse Events | Up to Week 52 | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an Improvement (Reduction) of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS) | At Week 4 | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Percentage of Participants Achieving an EASI 50 Response | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 50 response is defined as at least a 50% reduction (improvement) from Baseline in EASI score. |
| Percentage of Participants Achieving an EASI 90 Response | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score. |
| Percentage of Participants Achieving an EASI 100 Response | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1\], moderate \[2\], or severe \[3\]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. An EASI 100 response is defined as at least a 100% reduction (improvement) from Baseline in EASI score. |
| Absolute Change from Baseline for EASI | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1)\] moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement. |
| Percent Change From Baseline in EASI Score | At Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none \[0\], mild \[1)\] moderate \[2\], or severe \[3\]) for Redness (erythema, inflammation), Thickness (induration, papulation, swelling - acute eczema), Scratching (excoriation), and Lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease; a negative change from Baseline indicates improvement. |
| Absolute Change from Baseline in Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) | At Week 16 | The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: 0 - Clear: No inflammatory signs of AD; 1. \- Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification; 2. \- Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting; 3. \- Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present; 4. \- Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present. |
| Percentage of Participants Achieving a Validated Investigator´s Global Assessment for AD (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points | At Week 16 | The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: * 0 - Clear: No signs of AD; * 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification; \- 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification. No oozing or crusting; * 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting; * 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting. |
| Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS) | At Week 16 | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Absolute Change From Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS) | At Week 16 | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Absolute Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement | At Week 16 | Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA. |
| Percent Change from Baseline in Body Surface Area (BSA) of Atopic Dermatitis (AD) Involvement | At Week 16 | Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA. |
Countries
Japan, South Korea, United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed