14 CLINICAL STUDIES

Plaque Psoriasis

In two multicenter, randomized, double-blind, placebo-controlled trials (Trial 2 [NCT01722331] and Trial 3 [NCT01729754]), 926 subjects were treated with ILUMYA 100 mg (N=616) or placebo (N=310). Subjects had a Physician Global Assessment (PGA) score of ≥3 (moderate) on a 5-point scale of overall disease severity, Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum body surface area (BSA) involvement of 10%. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded.

In both trials, subjects were randomized to either placebo or ILUMYA (100 mg at Week 0, Week 4, and every twelve weeks thereafter [Q12W]) up to 64 weeks.

Trials 2 and 3 assessed the changes from baseline to Week 12 in the two co-primary endpoints:

PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score.
PGA of 0 (“cleared”) or 1 (“minimal”), the proportion of subjects with a PGA of 0 or 1 and at least a 2-point improvement.

Other evaluated outcomes in Trials 2 and 3 included the proportion of subjects who achieved a reduction from baseline in PASI score of at least 90% (PASI 90) and a reduction of 100% in PASI score (PASI 100) at Week 12 and maintenance of efficacy up to Week 64.

In both trials, subjects in the ILUMYA 100 mg and placebo treatment groups were predominantly men (69%) and White (80%), with a mean age of 46 years. At baseline, these subjects had a median affected BSA of 27%, a median PASI score of 17.8, and approximately 33% had a PGA score of 4 (“marked”) or 5 (“severe”). Approximately 34% had received prior phototherapy, 39% had received prior conventional systemic therapy, and 18% had received prior biologic therapy for the treatment of psoriasis. Approximately 16% of subjects had a history of psoriatic arthritis.

Clinical Response at Week 12

The results of Trials 2 and 3 are presented in Table 2.

Table 2: Efficacy Results at Week 12 in Adults with Plaque Psoriasis in Trials 2 and 3 (NRI*)
	Trial 2 (NCT01722331)		Trial 3 (NCT01729754)
* NRI = Non-Responder Imputation † Co-Primary Endpoints ‡ PGA score of 0 (“cleared”) or 1 (“minimal”)
	ILUMYA 100 mg (N=309) n (%)	Placebo (N=154) n (%)	ILUMYA 100 mg (N=307) n (%)	Placebo (N=156) n (%)
PGA of 0 or 1†,‡	179 (58)	11 (7)	168 (55)	7 (4)
PASI 75†	197 (64)	9 (6)	188 (61)	9 (6)
PASI 90	107 (35)	4 (3)	119 (39)	2 (1)
PASI 100	43 (14)	2 (1)	38 (12)	0 (0)

Examination of age, gender, race, and previous treatment with a biologic did not identify differences in response to ILUMYA among these subgroups at Week 12.

Maintenance of Response and Durability of Response

In Trial 2, subjects originally randomized to ILUMYA and who were responders at Week 28 (i.e., PASI 75) were re-randomized to an additional 36 weeks of either maintaining the same dose of ILUMYA Q12W (every twelve weeks) or placebo.

At Week 28, 229 (74%) subjects treated with ILUMYA 100 mg were PASI 75 responders. At Week 64, 84% of subjects who continued on ILUMYA 100 mg Q12W maintained PASI 75 compared to 22% of subjects who were re-randomized to placebo. In addition, for subjects who were re-randomized and also had a PGA score of 0 or 1 at Week 28, 69% of subjects who continued on ILUMYA 100 mg Q12W maintained this response (PGA 0 or 1) at Week 64 compared to 14% of subjects who were re-randomized to placebo.

For PASI 75 responders at Week 28 who were re-randomized to treatment withdrawal (i.e., placebo), the median time to loss of PASI 75 was approximately 20 weeks.

In addition, for subjects who were re-randomized to placebo and also had a PGA score of 0 or 1 at Week 28, the median time to loss of PGA score of 0 or 1 was approximately 16 weeks.

Psoriasis of the Scalp

In a multicenter, randomized, double-blind, placebo-controlled trial (Trial 4 [NCT03897088]) 231 subjects with moderate to severe psoriasis of the scalp (IGA Scalp score of 3 or 4) were treated subcutaneously with ILUMYA 100 mg (n=117) or placebo (n=114) at Weeks 0 and 4. Of the 231 randomized subjects, 217 subjects completed Part 1 (Day 1 to Week 16). In Part 2 of the trial, subjects previously randomized to placebo were switched to ILUMYA 100 mg at Weeks 16, 20, 32, and 44, and those in the ILUMYA 100 mg arm continued to receive ILUMYA 100 mg at Weeks 16, 28, 40, and 52.

The trial population was 79% White, 8% Black or African American, 6% Asian, 3% Native Hawaiian or Other Pacific Islander, 2% American Indian or Alaska Native, and 2% Other; for ethnicity, 65% of subjects identified as Not Hispanic or Latino. The trial population was 60% male and the mean age was 45 years. At baseline, these subjects had a median affected scalp surface area of 50%, a median PASI score of 16.7, and IGA Scalp score of 3 (“moderate”) or 4 (“severe”) in 81% and 16%, respectively.

The primary endpoint was the proportion of subjects with IGA Scalp score of “clear” and “almost clear” with at least 2-point reduction from Baseline at Week 16.

Other evaluated outcomes included the proportion of subjects achieving a) Psoriasis Scalp Severity Index (PSSI) 90 (≥90% improvement from Baseline in PSSI) at Week 16; b) PSSI 90 at Week 12; and c) IGA Scalp score of “clear” or “almost clear” with at least 2-point reduction from Baseline at Week 12.

The efficacy results from Trial 4 are presented in Table 3.

Table 3: Efficacy Results for Primary and Secondary Endpoints in Subjects with Moderate to Severe Psoriasis of the Scalp in Trial 4 (mITT, NRI*)

	Trial 4 (NCT03897088)
Note: IGA = Investigator Global Assessment. PSSI = psoriasis scalp severity index. * NRI = Non-responder imputation; mITT = modified Intent-to-treat, all randomized subjects, excluding subjects enrolled early in the trial evaluated under a different IGA Scalp scale.
	ILUMYA 100 mg (N=89) n (%)	Placebo (N=82) n (%)
Primary Endpoint
IGA Scalp Response Rate for score 0 or 1 (clear or almost clear) at Week 16 with at least 2-point reduction from baseline score	44 (49)	6 (7)
Secondary Endpoints
PSSI 90 Response Rate at Week 16	54 (61)	4 (5)
IGA Scalp Response Rate for score 0 or 1 (clear or almost clear) at Week 12 with at least 2-point reduction from baseline score	41 (46)	4 (5)
PSSI 90 Response Rate at Week 12	43 (48)	2 (2)