Table 1. Key features of 10 sponsor-initiated studies of infliximab in IBD.
| Study (reference) | Pt. population | Study design | Treatment regimens (no. of pts. evaluated) | AE reporting period (wks) |
|---|---|---|---|---|
| Smaller trials of infliximab in IBD | ||||
| C0168T08 (15) | Severe CD (CDAI >150) refractory to corticosteroid therapy | Phase 1, SC, OL, single dose | Grp 1: Infliximab 10 mg/kg (n=8)Grp 2: Infliximab 20 mg/kg (n=2) | 8 |
| C0168T11 (10) | Moderate-to-severea CD | Phase 2, MC, OL, single dose, sequential dose-escalating trial | Grp 1: Infliximab 1 mg/kg (n=5) | 12 |
| Grp 2: Infliximab 5 mg/kg (n=5) | ||||
| Grp 3: Infliximab 10 mg/kg (n=5) | ||||
| Grp 4: Infliximab 20 mg/kg (n=6) | ||||
| C0168T16 (10,12,14) | Moderate-to-severea CD | Phase 2/3, MC, DB, PC, with initial dose-ranging treatment phase followed by repeated-treatment phase plus OL treatment for safety assessments | Initial dose-ranging phase (single dose)Grp 1: Placebo (n=25)Grp 2: Infliximab 5 mg/kg (n=27)Grp 3: Infliximab 10 mg/kg (n=28)Grp 4: Infliximab 20 mg/kg (n=28) | 16 (n=35) and 48 (n=73) |
| Open-label phase: Infliximab 10 mg/kg (n=48) | ||||
| Repeated-treatment phase (4 DB infusions)Grp 1: Infliximab 10 mg/kg q8wks (n=37)Grp 2: Placebo q8wks (n=36) | ||||
| C0168T20 (11) | Fistulizing CD | MC, DB, PC, randomized phase 3 trial | Grp 1: Infliximab 10 mg/kg at wks 0, 2, 6 (n=32) | 52 |
| Grp 2: Infliximab 5 mg/kg at wks 0, 2, 6 (n=31) | ||||
| Grp 3: Placebo at wks 0, 2, 6 (n=31) | ||||
| C0168T12 (13) | Active UC (modified Truelove and Witts score >10) | MC, DB, PC, randomized phase 2 trial | Single dose of:Grp 1: Placebo (n=3)Grp 2: Infliximab 5 mg/kg (n=3)Grp 3: Infliximab 10 mg/kg (n=3)Grp 4: Infliximab 20 mg/kg (n=2) | 12 |
| Pivotal phase 3 trials of infliximab in IBD | ||||
| ACCENT I (5,6) |
Moderate-to-severea CD |
MC, DB, PC, phase 3 randomized trialAZA, 6-MP, MTX, corticosteroids allowed but not randomized treatments |
All pts.: Infliximab 5 mg/kg at wk 0 (n=573)Grp 1: Placebo at wks 2, 6, and q8wks through wk 46 (n=188)Grp 2: Infliximab 5 mg/kg at wks 2, 6, and q8wks through wk 46 (n=192)Grp 3: Infliximab 5 mg/kg at wks 2 and 6, then 10 mg/kg q8wks through wk 46 (n=193) |
54 |
| ACCENT II (7) | Fistulizing CD | MC, DB, PC, phase 3 randomized trial | All pts.: Infliximab 5 mg/kg at wks 0, 2, 6 (n=306) | 54 |
| AZA, 6-MP, MTX, corticosteroids allowed but not randomized treatments | Grp 1: Placebo at wk 14 and q8wks through wk 46 (crossover to 5 mg/kg possible; n=143 for placebo maintenance) | |||
| Grp 2: Infliximab 5 mg/kg at wk 14 and q8wks through wk 46 (crossover to 10 mg/kg possible; n=139 for infliximab maintenance) | ||||
| SONIC (8) | Moderate-to-severeb CD | MC, DB, ACC, phase 3 randomized trial | Grp 1: AZA 2.5 mg/kg capsules/placebo infusions (n=161) | 54c |
| Naïve to IMs and biologics; patients randomized to IM treatment | Grp 2: Placebo capsules/infliximab 5 mg/kg infusions (n=163)Grp 3: AZA 2.5 mg/kg capsules/infliximab 5 mg/kg infusions (n=179)Capsules (daily)/infusions (wks 0, 2, 6, q8wks through wk 22) | |||
| ACT 1 (9) | UC (364) in pts. with Mayo score of 6–12 pts., Mayo endoscopic subscore of ≥2, and an inadequate response to or tolerance of oral corticosteroids, 6-MP, and/or AZA | MC, DB, PC, phase 3 randomized trialAZA, 6-MP, corticosteroids allowed but not randomized treatments | Grp 1: Placebo at wks 0, 2, 6, and q8wks through wk 46 (n=121)Grp 2: Infliximab 5 mg/kg at wks 0, 2, 6, and q8wks through wk 46 (n=121)Grp 3: Infliximab 10 mg/kg at wks 0, 2, 6, and q8wks through wk 46 (n=122) | 54 |
| ACT 2 (9) | UC (364) in pts. with Mayo score of 6–12 pts., Mayo endoscopic subscore of ≥2, and an inadequate response to or tolerance of 5-ASAs, oral corticosteroids, 6-MP, and/or AZA | MC, DB, PC, phase 3 randomized trialAZA, 6-MP, corticosteroids allowed but not randomized treatments | Grp 1: Placebo at wks 0, 2, 6, and q8wks through wk 22 (n=123)Grp 2: Infliximab 5 mg/kg at wks 0, 2, 6, and q8wks through wk 22 (n=121)Grp 3: Infliximab 10 mg/kg at wks 0, 2, 6, and q8wks through wk 22 (n=120) | 54c |
ACC, active-comparator-controlled; AE, adverse event; 5-ASAs, 5-aminosalicylates; AZA, azathioprine; CD, Crohn's disease; CDAI, Crohn's disease activity index; DB, double-blind; IBD, inflammatory bowel disease; IM, immunomodulators; MC, multicenter; 6-MP, 6-mercaptopurine; MTX, methotrexate; OL, open label; PC, placebocontrolled; pts., patients; q8wks, every 8 weeks; SC, single center; UC, ulcerative colitis; wks, weeks.
a
Baseline CDAI score between 220 and 400, inclusive.
b
Baseline CDAI score between 220 and 450, inclusive.
c
Dosing in the SONIC and ACT 2 main studies ended with the week-22 infusion. Safety data from week 30 through week 54 were collected as part of study extensions.