XICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Animal studies have not been conducted to eva luate the carcinogenic or mutagenic potential ofILUMYA.
No effects on fertility parameters were observed in male or female cynomolgus monkeys that wereadministered tildrakizumab at subcutaneous or intravenous doses up to 140 mg/kg once every two weeksfor 3 months (133 or 155 times the MRHD, respectively, based on AUC comparison). The monkeys werenot mated to eva luate fertility.
14 CLINICAL STUDIES
In two multicenter, randomized, double-blind, placebo-controlled trials (Trial 2 [NCT01722331] andTrial 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 overalldisease 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 atleast a 2-point improvement.
Other eva luated outcomes in Trials 2 and 3 included the proportion of subjects who achieved areduction 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 predominantlymen (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 priorconventional 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)
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)
* NRI = Non-Responder Imputation
† Co-Primary Endpoints
‡ PGA score of 0 (“cleared”) or 1 (“minimal”)
Examination of age, gender, race, and previous treatment with a biologic did not identify differencesin response to ILUMYA among these subgroups at Week 12.
Maintenance of Response and Durability of ResponseIn 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 ILUMYAQ12W (every twelve wee |
