Table 3.

Clinical trials targeting CXCR3/CXCL10 in IBD.

Compound	Entry criteria	Cohort size and organisation	Primary endpoint	Potential expedients
A) Phase IIa68
BMS-936557 (IV)	Inclusion: UC; active flare despite 5-ASA or immunosuppressiona - Mayo score 6–10 - Mayo endoscopic sub-score ≥ 2 Exclusion: - Fulminant UC - Anti-TNFα therapy in preceding 8 w	- Placebo (n = 54) - BMS-936557 10 mg/kg (n = 55) Induction period; 8 w	Dec. in Mayo score ≥ 3 at 57 d + dec. in rectal bleed score ≥ 1 or absolute bleed score ≤ 1 - Placebo 35% - 10 mg/kg: 53% P = 0.083	Attaining primary endpoint by dose-response (drug trough drug values) - Placebo: 37% - 26–79 µg/mL: 53% - 79–105 µg/mL: 63% - 108–235 µg/mL: 88% Mucosal healing - Placebo: 35% - 26–79 µg/mL: 29% - 79–105 µg/mL: 44% - 108–235 µg/mL: 69%
B) Phase IIb69
BMS-936557 (IV) - Eldelumab	Inclusion: UC; moderate to severe activitya - Mayo score ≥ 6 - Mayo endoscopic subscore ≥ 2 - Inadequate response to existing medical therapy; any type Exclusion: - As above	- Placebo (n = 83) - Eldelumab 15 mg/kg (n = 84) - Eldelumab 25 mg/kg (n = 85) Induction period; 11 w	Mayo score < 2 by 11 w + no individual component > 1 - Placebo: 9.6% vs - 15 mg/kg: 13.1%; P = 0.515) - 25 mg/kg: 17.6%; P = 0.158)	Subgroup analysis of primary endpoint and mucosal healing greater compared with placebo in: (A) anti-TNFα naïve; and (B) immunomodulator-exposed subgroups
C) Phase IIa70
BMS-936557 (IV) - Eldelumab	Inclusion: Moderate to severe Crohn’s disease - CDAI 220 to 450 - CRP ≥ 5 mg/L, or - Faecal calprotectin > 250 µg/g, or - SES-CD of 2 to 3 - Insufficient response/intolerance to prednisolone (≥ 40 mg/d for 2 w (or equivalent) or immunomodulators Exclusion: - Penetrating disease or fibrotic stenosis - Surgery within 6 m of screening - Anti-TNFα therapy in preceding 8 w	- Placebo (n = 40) - Eldelumab 10 mg/kg (n = 40) - Eldelumab 20 mg/kg (n = 41)	1) Steady-state plasma concentration for induction- No statistically significant exposure-remission relationship with Eldelumab at 11 w OR: 1.06 (90% CI 0.96–1.18) 2) Efficacy: CDAI < 150 by 11 w; treatment differences - 10 mg/kg vs placebo: 9% - 20 mg/kg vs placebo: 13%	Composite endpoint analysis showed increased response rate for both doses vs placebo

5-ASA, 5-aminosalicylic acid; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; d, day; dec., decrease; IV, intravenous; m, month; SES-CD, simplified endoscopic score of Crohn’s disease; TNF, tumour necrosis factor; OR, odds ratio; UC, ulcerative colitis; w, week, IBD, inflammatory bowel disease; CRP, C-reactive protein.

^a2 w before drug administration and of ≥ 6 m duration.