Atopic Dermatitis
Conditions
Brief summary
The main purpose of this study is to describe the efficacy and safety of LY3454738 in adult participants with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGLY3454738
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Are candidates for systemic therapy. ISA specific: * Have moderate-to-severe AD, defined as meeting all of the following criteria, at the first dosing visit: * EASI score greater than or equal to (≥)16 * vIGA-AD score ≥3, and * ≥10% of BSA involvement (per EASI BSA). * Have applied at least 1 emollient every day for at least 2 weeks before the day of the first dose of study intervention in this ISA and agree to daily use of at least 1 emollient continuously throughout the study.
Exclusion criteria
ISA specific: * Have, in the screening period, any of the skin conditions, infections, or medical conditions listed under master IMMB. * Are currently being treated with topical or systemic therapy * Recent treatment with experimental (biologics and/or small molecules) - doesn't apply for subset of participants who must have been exposed to biologics and/or small molecules.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score. |
| Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16 | Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score. |
| Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16 | Week 16 | The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score. |
| Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16 | Week 16 | vIGA-AD is a standardized clinical tool used to measure the severity of AD. It is a static 5-point scale ranging from 0 to 4, used to grade overall disease severity. Higher viGA-AD scores represent more severe disease. The scale is as below: * 0-Clear: No inflammatory signs of atopic dermatitis (erythema, induration/papulation, lichenification, oozing/crusting). Post-inflammatory hyperpigmentation and/or hypopigmentation may be present. * 1-Almost Clear: Barely perceptible erythema, induration/papulation, and/or lichenification. No oozing/crusting. * 2-Mild: Slight but definite erythema (pink), induration/papulation, and/or lichenification. No oozing/crusting. * 3-Moderate: Clearly perceptible erythema (dull red), induration/papulation, and/or lichenification. Oozing and crusting may be present. * 4-Severe: Marked erythema (deep or bright red), induration/papulation, and/or lichenification. Disease is widespread in extent. Oozing or crusting may be present. |
| Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-50 responder is defined as a participant who achieves a ≥ 50% reduction from baseline in the EASI score. |
| Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants | Baseline, Week 16 | Mean percent change from baseline in EASI in biologic and small molecule naive participants was reported. |
| Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants | Baseline, Week 16 | Mean percent change from baseline in SCORAD in biologic and small molecule naive participants was reported. |
| Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16 | Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score. |
| Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16 | Day 113 post Day 1 Dose | PK: Serum trough concentrations of LY3454738 were reported. |
| Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline | Baseline, Week 16 | Percentage of biologic and small molecule naive participants achieving ≥4-point improvement from baseline in Itch NRS in the Subset of biologic and small molecule naive participants with ≥4-point Itch NRS at Baseline were reported. The Itch NRS is a an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating No itch and 10 indicating Worst itch imaginable. |
Countries
Canada, China, Hungary, Japan, Mexico, Poland, South Korea, Taiwan, United States
Participant flow
Recruitment details
Induction Period (16 weeks): Participants were randomly assigned to receive 75 mg or 300 mg or 800 mg of LY3454738 or placebo every 2 weeks (Q2W) subcutaneously (SC). Maintenance Period (28 weeks): At Week 16, participants who achieved a ≥50% improvement in EASI \[EASI-50\]) (responders) were reassigned as follows, continuing treatment through Week 40: • Responders from the 800 mg Q2W group were re-randomized to receive either 800 mg LY3454738 every 4 weeks (Q4W) or placebo Q4W. (continued)
Pre-assignment details
* Responders from 300 mg Q2W arm received 300 mg LY3454738 Q4W. * Responders from 75 mg Q2W arm received 150 mg LY3454738 Q4W. * Responders from placebo Q2W arm received placebo Q4W. Escape Arm: Participants who didn't achieve EASI-50 at Week 16 (induction non-responders) or who didn't achieve ≥25% improvement from baseline in EASI at Week 20, 24, 28, 32, or 36 (maintenance non-responders) were assigned to Escape Arm. These participants received LY3454738 800 mg Q4W through Week 40.
Participants by arm
| Arm | Count |
|---|---|
| Induction - Placebo Q2W Induction Period: (Baseline - Week 16): Participants received SC injections of Placebo Q2W from Baseline until Week 14. | 65 |
| Induction - LY3454738 75 mg Q2W Induction Period (Baseline - Week 16): Participants received 75 mg of LY3454738 given SC Q2W from Baseline until Week 14. | 31 |
| Induction - LY3454738 300 mg Q2W Induction Period (Baseline - Week 16): Participants received 300 mg of LY3454738 given SC Q2W from Baseline until Week 14. | 45 |
| Induction - LY3454738 800 mg Q2W Induction Period (Baseline - Week 16): Participants received 800 mg of LY3454738 given SC Q2W from Baseline until Week 14. | 93 |
| Total | 234 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Escape Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Escape Period | Discontinued Due to Failure to Achieve an EASI-50 Response | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Escape Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 31 |
| Escape Period | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Escape Period | Site Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Escape Period | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 34 |
| Escape Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 10 |
| Induction Period | Adverse Event | 3 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Assigned Treatment by Mistake | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lack of Efficacy | 3 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Study Terminated by Sponsor | 2 | 0 | 14 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Induction Period | Withdrawal by Subject | 4 | 3 | 4 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Maintenance Period | Enrolled to Escape Arm | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 4 | 4 | 0 |
| Maintenance Period | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Maintenance Period | Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 11 | 5 | 1 | 7 | 7 | 0 |
| Maintenance Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Induction - LY3454738 75 mg Q2W | Induction - LY3454738 300 mg Q2W | Induction - Placebo Q2W | Induction - LY3454738 800 mg Q2W | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 12.4 | 36.1 years STANDARD_DEVIATION 13.9 | 38.0 years STANDARD_DEVIATION 13.4 | 35.2 years STANDARD_DEVIATION 12.6 | 36.4 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 7 Participants | 12 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 40 Participants | 57 Participants | 80 Participants | 201 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 3 Participants | 4 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 25 Participants | 27 Participants | 49 Participants | 113 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 6 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 26 Participants | 37 Participants | 90 Participants |
| Region of Enrollment Canada | 3 Participants | 6 Participants | 5 Participants | 9 Participants | 23 Participants |
| Region of Enrollment China | 4 Participants | 1 Participants | 4 Participants | 8 Participants | 17 Participants |
| Region of Enrollment Hungary | 3 Participants | 0 Participants | 3 Participants | 5 Participants | 11 Participants |
| Region of Enrollment Japan | 2 Participants | 9 Participants | 8 Participants | 13 Participants | 32 Participants |
| Region of Enrollment Mexico | 7 Participants | 2 Participants | 4 Participants | 6 Participants | 19 Participants |
| Region of Enrollment Poland | 6 Participants | 8 Participants | 17 Participants | 22 Participants | 53 Participants |
| Region of Enrollment South Korea | 1 Participants | 9 Participants | 3 Participants | 10 Participants | 23 Participants |
| Region of Enrollment Taiwan | 2 Participants | 4 Participants | 8 Participants | 11 Participants | 25 Participants |
| Region of Enrollment United States | 3 Participants | 6 Participants | 13 Participants | 9 Participants | 31 Participants |
| Sex: Female, Male Female | 13 Participants | 21 Participants | 28 Participants | 39 Participants | 101 Participants |
| Sex: Female, Male Male | 18 Participants | 24 Participants | 37 Participants | 54 Participants | 133 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 31 | 0 / 45 | 0 / 93 | 0 / 22 | 0 / 13 | 0 / 8 | 0 / 20 | 0 / 19 | 0 / 105 |
| other Total, other adverse events | 35 / 65 | 19 / 31 | 20 / 45 | 52 / 93 | 13 / 22 | 7 / 13 | 4 / 8 | 7 / 20 | 6 / 19 | 39 / 105 |
| serious Total, serious adverse events | 3 / 65 | 1 / 31 | 1 / 45 | 1 / 93 | 1 / 22 | 1 / 13 | 0 / 8 | 1 / 20 | 0 / 19 | 0 / — |
Outcome results
Primary
Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16 | 14.3 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16 | 20.0 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16 | 17.2 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Eczema Area and Severity Index (EASI) 75 (≥75% Reduction in EASI Score) at Week 16 | 18.3 Percentage of participants |
Secondary
Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants
Mean percent change from baseline in EASI in biologic and small molecule naive participants was reported.
Time frame: Baseline, Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Induction - Placebo Q2W | Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants | -25.2 Percent change | Standard Error 7.1 |
| Induction - LY3454738 75 mg Q2W | Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants | -37.2 Percent change | Standard Error 6.39 |
| Induction - LY3454738 300 mg Q2W | Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants | -25.3 Percent change | Standard Error 6.83 |
| Induction - LY3454738 800 mg Q2W | Mean Percent Change From Baseline in EASI in Biologic and Small Molecule Naive Participants | -40.1 Percent change | Standard Error 4.76 |
95% CI: [-30.6, 6.6]
95% CI: [-19.4, 19.2]
95% CI: [-31.6, 1.7]
Secondary
Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants
Mean percent change from baseline in SCORAD in biologic and small molecule naive participants was reported.
Time frame: Baseline, Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Induction - Placebo Q2W | Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants | -16.6 Percent change | Standard Error 4.86 |
| Induction - LY3454738 75 mg Q2W | Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants | -21.0 Percent change | Standard Error 4.65 |
| Induction - LY3454738 300 mg Q2W | Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants | -15.2 Percent change | Standard Error 5.01 |
| Induction - LY3454738 800 mg Q2W | Mean Percent Change From Baseline in SCORAD in Biologic and Small Molecule Naive Participants | -26.6 Percent change | Standard Error 3.58 |
95% CI: [-17.6, 8.7]
95% CI: [-12.3, 15.1]
95% CI: [-21.8, 1.9]
Secondary
Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Time frame: Week 16
Population: All biologic and small-molecule-experienced participants who were randomly assigned to study intervention and took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16 | 20.0 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16 | 0.0 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16 | 6.2 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Experienced Participants Achieving EASI-75 at Week 16 | 12.1 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline
Percentage of biologic and small molecule naive participants achieving ≥4-point improvement from baseline in Itch NRS in the Subset of biologic and small molecule naive participants with ≥4-point Itch NRS at Baseline were reported. The Itch NRS is a an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating No itch and 10 indicating Worst itch imaginable.
Time frame: Baseline, Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug in the subset of participants with ≥4-point Itch NRS at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline | 12.9 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline | 24.0 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline | 5.3 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving ≥4-point Improvement From Baseline in Itch Numeric Rating Scale (NRS) in the Subset of Biologic and Small Molecule Naive Participants With ≥4-point Itch NRS at Baseline | 6.8 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-50 responder is defined as a participant who achieves a ≥ 50% reduction from baseline in the EASI score.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16 | 28.6 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16 | 40.0 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16 | 24.1 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-50 (≥ 50% Reduction in EASI Score) at Week 16 | 45.0 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI-90 responder is defined as a participant who achieves a ≥ 90% reduction from baseline in the EASI score.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16 | 8.6 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16 | 3.3 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16 | 10.3 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving EASI-90 (≥ 90% Reduction in EASI Score) at Week 16 | 11.7 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the SCORAD score.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16 | 2.9 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16 | 0.0 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16 | 0.0 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORAD-90 at Week 16 | 1.7 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16 | 5.7 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16 | 3.3 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16 | 3.4 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving SCORing Atopic Dermatitis (SCORAD) 75 at Week 16 | 6.7 Percentage of participants |
Secondary
Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16
vIGA-AD is a standardized clinical tool used to measure the severity of AD. It is a static 5-point scale ranging from 0 to 4, used to grade overall disease severity. Higher viGA-AD scores represent more severe disease. The scale is as below: * 0-Clear: No inflammatory signs of atopic dermatitis (erythema, induration/papulation, lichenification, oozing/crusting). Post-inflammatory hyperpigmentation and/or hypopigmentation may be present. * 1-Almost Clear: Barely perceptible erythema, induration/papulation, and/or lichenification. No oozing/crusting. * 2-Mild: Slight but definite erythema (pink), induration/papulation, and/or lichenification. No oozing/crusting. * 3-Moderate: Clearly perceptible erythema (dull red), induration/papulation, and/or lichenification. Oozing and crusting may be present. * 4-Severe: Marked erythema (deep or bright red), induration/papulation, and/or lichenification. Disease is widespread in extent. Oozing or crusting may be present.
Time frame: Week 16
Population: All biologic and small-molecule-naive participants who were randomly assigned to study intervention and took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction - Placebo Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16 | 8.6 Percentage of participants |
| Induction - LY3454738 75 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16 | 6.7 Percentage of participants |
| Induction - LY3454738 300 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16 | 6.9 Percentage of participants |
| Induction - LY3454738 800 mg Q2W | Percentage of Biologic and Small Molecule Naive Participants Achieving Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 at Week 16 | 15.0 Percentage of participants |
Secondary
Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16
PK: Serum trough concentrations of LY3454738 were reported.
Time frame: Day 113 post Day 1 Dose
Population: All biologic and/or small molecule experienced or biologic-and-small-molecule naïve participants who were randomly assigned to study intervention and took at least 1 dose of LY3454738 and had evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Induction - Placebo Q2W | Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16 | 12.1 micrograms per milliliter (μg/mL) | Standard Deviation 7.01 |
| Induction - LY3454738 75 mg Q2W | Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16 | 56.2 micrograms per milliliter (μg/mL) | Standard Deviation 18.5 |
| Induction - LY3454738 300 mg Q2W | Pharmacokinetics (PK): Serum Trough Concentrations of LY3454738 at Week 16 | 151 micrograms per milliliter (μg/mL) | Standard Deviation 56.2 |