14 CLINICAL STUDIES

14.1 Atopic Dermatitis

Two double-blind, randomized, vehicle-controlled trials of identical design (TRuE-AD1 and TRuE-AD2, NCT03745638 and NCT03745651, respectively) enrolled a total of 1249 adult and pediatric subjects aged 12 and older. A total of 20% of subjects were 12 to 17 years of age and 9% were 65 years or older. Females constituted 62% of subjects, 70% of subjects were White, 23% were Black, and 4% were Asian. Subjects had affected body surface area (BSA) of 3 to 20%, and an Investigator’s Global Assessment (IGA) score of 2 (mild) to 3 (moderate) on a severity scale of 0 to 4. At baseline, subjects had a mean affected BSA of 9.8% and 39% had affected areas on the face, 25% of subjects had an IGA score of 2 and 75% had a score of 3. The baseline Itch Numerical Rating Scale (Itch NRS), defined as the 7-day average of the worst level of itch intensity in the last 24 hours, was 5 on a scale of 0 to 10.

In both trials, subjects were randomized 2:2:1 to treatment with OPZELURA, ruxolitinib cream, 0.75%, or vehicle cream twice daily (BID) for 8 weeks. The primary efficacy endpoint was the proportion of subjects at week 8 achieving IGA treatment success (IGA-TS) defined as a score of 0 (clear) or 1 (almost clear) with ≥ 2 grade improvement from baseline. Efficacy was also assessed using a ≥ 4-point improvement in Itch NRS.

Efficacy results for OPZELURA from the two trials are summarized in Table 3.

Table 3: Efficacy Results at Week 8 in Subjects with Atopic Dermatitis (TRuE-AD1 and TRuE-AD2)
* Defined as an IGA score of 0 or 1 with a ≥ 2-grade improvement from baseline † N = subjects with a baseline Itch NRS score ≥ 4.
	TRuE-AD1			TRuE-AD2
	OPZELURA (N = 253)	Vehicle (N = 126)	Treatment Difference and 95% Confidence Interval	OPZELURA (N = 228)	Vehicle (N = 118)	Treatment Difference and 95% Confidence Interval
IGA-TS*	53.8% (136/253)	15.1% (19/126)	38.9% (30.3%, 47.4%)	51.3% (117/228)	7.6% (9/118)	44.1% (36.2%, 52.0%)
Itch NRS (≥ 4 point reduction) (n/N)†	52.2% (84/161)	15.4% (12/78)	36.7% (25.5%, 48.0%)	50.7% (74/146)	16.3% (13/80)	35.8% (24.4%, 47.2%)

14.2 Nonsegmental Vitiligo

Two double-blind, randomized, vehicle-controlled trials of identical design (TRuE‑V1 and TRuE‑V2, NCT04052425 and NCT04057573, respectively) enrolled a total of 674 adult and pediatric subjects aged 12 years and older (11% of subjects were 12 to 17 years of age and 7% were 65 years or older). Females constituted 53% of subjects, 82% of subjects were White, 5% were Black, and 4% were Asian. Fitzpatrick skin types included I (2%), II (30%), III (40%), IV (19%), V (7%), or VI (2%). Subjects had depigmented areas affecting ≥ 0.5% facial body surface area (F-BSA), ≥ 3% non-facial BSA, and total body vitiligo area (facial and non-facial, including hands, feet, upper and lower extremities, and trunk body areas) of up to 10% BSA. At baseline, subjects had a mean affected F-BSA of 1% and a mean affected total BSA of 7.4%. Phototherapy was not permitted during the trial. The mean time since diagnosis of nonsegmental vitiligo was 14.8 years prior to subjects enrolling in the trials.

In both trials, subjects were randomized 2:1 to treatment with OPZELURA or vehicle cream twice daily (BID) for 24 weeks followed by an additional 28 weeks of treatment with OPZELURA BID for all subjects. Lesions on the face were assessed with the facial Vitiligo Area Scoring Index (F-VASI) and lesions on the total body (including the face) were assessed with the total body Vitiligo Area Scoring Index (T-VASI). The primary efficacy endpoint was the proportion of subjects achieving at least 75% improvement in F-VASI (F-VASI75) at Week 24. The proportion of participants achieving at least 90% improvement in F-VASI (F-VASI90) was also evaluated.

Efficacy results for OPZELURA at Week 24 from the two trials are summarized in Table 4. The percentage of subjects who achieved F-VASI75 and T-VASI75 (at least 75% improvement in T‑VASI) over the 52-week treatment period in both trials are shown in Figure 1 and Figure 2.

Table 4: Efficacy Results at Week 24 in Subjects with Nonsegmental Vitiligo (TRuE-V1 and TRuE-V2)
	TRuE-V1			TRuE-V2
	OPZELURA (N = 221)	Vehicle (N = 109)	Treatment Difference and 95% Confidence Interval	OPZELURA (N = 229)	Vehicle (N = 115)	Treatment Difference and 95% Confidence Interval
F-VASI75	29.9%	7.5%	22.5% (14.2%, 30.8%)	29.9%	12.9%	16.9% (7.8%, 26.0%)
F-VASI90	15.5%	2.2%	13.3% (7.5%, 19.1%)	15.4%	1.9%	13.5% (7.7%, 19.3%)

Percentage of Subjects with Nonsegmental Vitiligo Achieving F-VASI75 During the 52-Week Treatment Period (TRuE V1 and TRuE V2 Combined)

Percentage of Subjects with Nonsegmental Vitiligo Achieving T-VASI75 During the 52-Week Treatment Period (TRuE V1 and TRuE V2 Combined)