14 CLINICAL STUDIES

14.1 Plaque Psoriasis

Two multicenter, randomized, double-blind, vehicle-controlled trials (DERMIS-1 [NCT04211363] and DERMIS-2 [NCT04211389]) enrolled a total of 881 adult and pediatric subjects 6 years of age or older with mild to severe plaque psoriasis. Subjects were randomized 2:1 to receive ZORYVE cream, 0.3%, or vehicle cream applied topically once daily for 8 weeks. The median age of the trial population was 47 years (range 6 to 88 years of age). The trial population was 64% male and 36% female; 82.3% were White, 7.1% Asian, 3.6% Black or African American, 0.9% Native Hawaiian or Other Pacific Islander, 0.7% American Indian or Alaska Native, 0.5% more than one race, 3.3% Other, and missing in 1.6% of subjects. For ethnicity, 75.7% of subjects identified as Not Hispanic or Latino, 24.1% identified as Hispanic or Latino, and 0.2% were unknown. The median body surface area (BSA) affected of the trial population was 5.5% (range 2% to 20%). At baseline, 16% of subjects had an Investigator's Global Assessment (IGA) score of 2 (mild), 76% had an IGA score of 3 (moderate), and 8% had an IGA score of 4 (severe). One hundred seventy-nine (20%) subjects had a baseline intertriginous IGA (I-IGA) score of 2 or higher (mild), and 678 (77%) subjects had a baseline Worst Itch-Numeric Rating Scale (WI-NRS) score of 4 or higher on a scale of 0 to 10.

The primary endpoint was the proportion of subjects who achieved IGA treatment success at Week 8 (Table 3). Success was defined as a score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade improvement from baseline.

Table 3: IGA Treatment Success at Week 8 in Subjects with Mild to Severe Plaque Psoriasis in Trials DERMIS-1 and DERMIS-2
	DERMIS-1		DERMIS-2
	ZORYVE Cream, 0.3%	Vehicle Cream	ZORYVE Cream, 0.3%	Vehicle Cream
Subjects randomized	N=286	N=153	N=290	N=152
Abbreviations: CI = Confidence Interval
* IGA treatment success was defined as an IGA score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade IGA score improvement from baseline at Week 8 (Multiple Imputation). † Treatment difference and 95% CI are based on the CMH method stratified by site, baseline IGA, and baseline intertriginous involvement.
IGA success*	41.5%	5.8%	36.7%	7.1%
Difference from vehicle (95% CI)†	39.7% (32.4%, 47.0%)		29.5% (21.5%, 37.6%)

Secondary endpoints included the proportion of subjects that achieved I-IGA success at Week 8 and WI-NRS success sequentially at Weeks 8, 4, and 2 (see Figure 1). WI-NRS success was defined as a reduction of at least 4 points from baseline in subjects with a baseline WI-NRS score of at least 4.

Figure 1: WI-NRS Success Over Time in Subjects with Mild to Severe Plaque Psoriasis in Trials DERMIS-1 and DERMIS-2*
†The treatment difference at Week 2 in DERMIS-1 was not statistically significant.
* WI-NRS success is a reduction of at least 4 points in subjects with a WI-NRS score of 4 or higher at baseline.

Among subjects with an I-IGA score of at least 2 (mild) at baseline (approximately 22% of subjects in DERMIS-1 and 19% in DERMIS-2), there was a higher percentage of subjects who achieved I-IGA success at Week 8 in the group who received ZORYVE cream, 0.3%, compared to the group who received vehicle cream (DERMIS-1: 71.5% vs. 13.8%; DERMIS-2: 67.5% vs. 17.4%).

14.2 Atopic Dermatitis

Two multicenter, randomized, double-blind, vehicle-controlled trials (INTEGUMENT-1 [NCT04773587] and INTEGUMENT-2 [NCT04773600]) enrolled a total of 1337 adult and pediatric subjects 6 years of age and older (615 subjects were 6 to 17 years of age) with mild to moderate atopic dermatitis. Subjects were randomized 2:1 to receive ZORYVE cream, 0.15%, or vehicle cream applied once daily for 4 weeks. The median age of the trial population was 20 years (range 6 to 91 years of age). The trial population was 57% female; 59.5% were White, 20.3% Black or African American, 13.2% Asian, 3.4% Other, 2.8% more than one race, 0.6% American Indian or Alaska Native, and 0.1% Native Hawaiian or Other Pacific Islander. For ethnicity, 82.8% of subjects identified as Not Hispanic or Latino, 16.6% identified as Hispanic or Latino, and 0.6% were unknown. At baseline, subjects had a mean affected BSA of 14% (range of 3% to 88%), and 42% had facial involvement. At baseline, 24% of subjects had a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 2 (mild), and 76% had a vIGA-AD score of 3 (moderate). Eight hundred thirteen (60.8%) subjects 12 years of age and older had a baseline WI-NRS score of 4 or higher on a scale of 0 to 10.

The primary endpoint was the proportion of subjects who achieved vIGA-AD treatment success at Week 4 (Table 4). Success was defined as a score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade improvement from baseline.

Secondary endpoints included the proportion of subjects that achieved vIGA-AD success at Weeks 2 and 1 (Figure 2) and WI-NRS success at Weeks 4, 2, and 1 (Figure 3). WI-NRS success was defined as a reduction of at least 4 points from baseline in subjects 12 years of age or older with a baseline WI-NRS score of at least 4.

Table 4: Efficacy Results at Week 4 in Subjects with Mild to Moderate Atopic Dermatitis in Trials INTEGUMENT-1 and INTEGUMENT-2
	INTEGUMENT-1		INTEGUMENT-2
	ZORYVE Cream, 0.15%	Vehicle Cream	ZORYVE Cream, 0.15%	Vehicle Cream
Abbreviations: CI = Confidence Interval
* vIGA-AD success was defined as a vIGA-AD score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade vIGA-AD score improvement from baseline at Week 4 (Multiple Imputation). † The difference in percent and related 95% CIs are Mantel-Haenszel estimates stratified by pooled study site and vIGA-AD randomization strata. ‡ WI-NRS success was defined as a reduction of at least 4 points from baseline for subjects 12 years of age or older with a baseline score of at least 4.
Subjects randomized	N=433	N=221	N=451	N=232
vIGA-AD success*	32.0%	15.2%	28.9%	12.0%
Difference from vehicle (95% CI)†	17.4% (11.09%, 23.75%)		16.5% (10.61%, 22.42%)
Subjects ≥12 years randomized with baseline WI-NRS ≥4	N=278	N=135	N=264	N=136
WI-NRS success‡	33.6%	20.7%	30.2%	12.4%
Difference from vehicle (95% CI)†	13.3% (4.01%, 22.60%)		15.0% (6.52%, 23.54%)

Figure 2: vIGA-AD Success Over Time in Subjects with Mild to Moderate Atopic Dermatitis in Trials INTEGUMENT-1 and INTEGUMENT-2*
†The treatment difference at Week 1 in INTEGUMENT-2 was not statistically significant.
* vIGA-AD success was defined as a vIGA-AD score of "Clear" (0) or "Almost Clear" (1), plus a 2-grade vIGA-AD score improvement from baseline at Week 4 (Multiple Imputation).

Figure 3: WI-NRS Success Over Time in Subjects with Mild to Moderate Atopic Dermatitis in Trials INTEGUMENT-1 and INTEGUMENT-2*
* WI-NRS success in subjects 12 years of age or older is a reduction of at least 4 points in subjects with a WI-NRS score of 4 or higher at baseline.