Table 2.
Phase II and III studies pertinent to clinical pharmacology characterization
| Study (phase) | Objective(s) | Study design | Dosage regimen and route of administration | Duration of dosing (study duration) | No. of subjects | Analyses |
|---|---|---|---|---|---|---|
| 3 (phase II) |
To assess the efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe chronic plaque psoriasis To assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of risankizumab |
A randomized, parallel-arm, dose-ranging, multiple-dose, active comparator-controlled, double-blind study in psoriasis patients |
Subjects were randomized 1:1:1:1 into the following dose groups: Risankizumab 18 mg SC (18 mg × one injection) at week 0 (n = 43) Risankizumab 90 mg SC (90 mg × 1 injection) at weeks 0, 4, and 16 (n = 41) Risankizumab 180 mg SC (90 mg × two injections) at weeks 0, 4. and 16 (n = 42) Ustekinumab 45 or 90 mg SC at weeks 0, 4, and 16 (n = 40) |
Up to 16 weeks (48 weeks for subjects not enrolling in OLE) | 166 Treated; 157 completed | PopPK, ER, IIA |
| UltIMMa-1 (4, phase III) | To assess the efficacy and safety of risankizumab compared with ustekinumab and placebo in patients with moderate-to-severe chronic plaque psoriasis | Placebo and active-controlled, confirmatory, double-blind, double-dummy, randomized, parallel design comparison of risankizumab with ustekinumab and placebo over 52 weeks in psoriasis patients |
Subjects were randomized at a ratio of 3:1:1 to one of three treatment arms: Risankizumab 150 mg (75 mg × two injections) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 304) Ustekinumab 45 or 90 mg SC at weeks 0 and 4, and every 12 weeks thereafter (n = 100) Placebo SC at weeks 0 and 4, followed by risankizumab 150 mg SC every 12 weeks thereafter (n = 102) |
40 weeks (52 weeks; 56 weeks for subjects not enrolling in OLE]) | 506 Treated; 478 completed | PopPK, ER, IIA |
| UltIMMa-2 (5, phase III) | To assess the efficacy and safety of risankizumab compared with ustekinumab and placebo in patients with moderate-to-severe chronic plaque psoriasis | Placebo and active-controlled, confirmatory, double-blind, double-dummy, randomized, parallel design comparison of risankizumab and ustekinumab and placebo over 52 weeks in psoriasis patients |
Subjects were randomized at a ratio of 3:1:1 to one of three treatment arms: Risankizumab 150 mg (75 mg × two injections) SC at week 0 and 4, and every 12 weeks thereafter (n = 294) Ustekinumab 45 or 90 mg SC at weeks 0 and 4, then every 12 weeks thereafter (n = 99) Placebo SC at weeks 0 and 4, followed by risankizumab 150 mg SC every 12 weeks thereafter (N = 98) |
40 weeks (52 weeks; 56 weeks for subjects not enrolling in OLE) | 491 Treated; 459 completed | PopPK, ER, IIA |
| IMMhance (6, phase III) | To assess the safety and efficacy of risankizumab in comparison with placebo in patients with moderate-to-severe chronic plaque psoriasis. To assess the maintenance of response following drug withdrawal and the response after retreatment in subjects who experience relapse after drug withdrawal | Placebo-controlled, confirmatory, double-blind, randomized withdrawal and retreatment study |
Subjects were randomized at a ratio of 4:1 to one of two treatment arms: Risankizumab 150 mg (75 mg × two injections) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 407) Placebo SC at weeks 0 and 4 followed by risankizumab 150 mg SC every 12 weeks thereafter (n = 100) |
88 weeks (104 weeks) | 507 Treated; ongoing | PopPK, ER, IIA |
| IMMvent (7, phase III) | To assess the efficacy and safety of risankizumab compared with adalimumab in patients with moderate-to-severe chronic plaque psoriasis | Active-controlled, double-blind, double-dummy, randomized, parallel design comparison of risankizumab and adalimumab over 44 weeks in psoriasis patients |
Subjects were randomized at a ratio of 1:1 to one of two treatment arms: Risankizumab 150 mg (75 mg × two injections) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 301) Adalimumab 80 mg SC at randomization; then 40 mg SC at week 1, and thereafter every other week (n = 304) |
32 weeks for risankizumab and 41 weeks for adalimumab (44 weeks; 48 weeks for subjects not enrolling in OLE) | 605 Treated; 550 completed | PopPK, ER, IIA |
| 9 (phase II/III; Japan) | To assess the efficacy and safety of two different dose regimens of risankizumab compared with placebo in Japanese subjects with moderate-to-severe chronic plaque psoriasis (with or without psoriatic arthritis) | Randomized, double-blind, double-dummy, placebo-controlled, parallel design study comparing two different dose regimens of risankizumab with placebo |
Subjects were randomized at a ratio of 2:2:1:1 to one of four treatment arms: Risankizumab 75 mg (75 mg × one injection) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 58) Risankizumab 150 mg (75 mg × two injections) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 55) Placebo with risankizumab 75 mg (75 mg × one injection) SC at week 16 and every 12 weeks thereafter (n = 27) Placebo with risankizumab 150 mg (75 mg × two injections) SC at week 16 and every 12 weeks thereafter (n = 27) |
40 weeks (52 weeks; 56 weeks for subjects not enrolling in OLE) | 171 Treated; ongoing | PopPK (Japan only)a, ER (Japan only)a, IIA (Japan only)a |
| 10 (phase III; Japan) | To assess the safety and efficacy of two different dose regimens of risankizumab for Japanese subjects with GPP or EP | Randomized, open-label study of two different dose regimens of risankizumab in subjects with GPP or EP |
Subjects were randomized at a ratio of 1:1 to one of two treatment arms: Risankizumab 75 mg (75 mg × one injection) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 9) Risankizumab 150 mg (75 mg × two injections) SC at weeks 0 and 4, and every 12 weeks thereafter (n = 8) |
172 weeks (188 weeks) | 17 Treated; ongoing | PopPK (Japan)a, ER for safety only (Japan)a, IIA (Japan)a |
OLE open-label extension, EP erythrodermic psoriasis, GPP generalized pustular psoriasis, SC subcutaneous, PopPK population pharmacokinetic analyses, ER exposure–response analyses (for both efficacy and safety, unless otherwise noted), IIA integrated immunogenicity analyses
aAll global data were included in the Japan analyses, but the two Japan studies were only included in the Japan analyses