Efficacy and safety of the interleukin-10-fragment F8 fusion protein PF-06687234 as add-on therapy to infliximab in patients with active ulcerative colitis: a randomized, phase IIa clinical trial.

BACKGROUND

PF-06687234 is a novel, human, single-chain variable fragment cytokine fusion protein comprising the antibody fragment F8 and the immunoregulatory cytokine interleukin-10.

OBJECTIVES

We evaluated the efficacy and safety of PF-06687234 as an add-on therapy to infliximab in participants with active ulcerative colitis (UC).

DESIGN

This phase IIa, double-blind, placebo-controlled, parallel-group, multicenter study randomized (1:1) participants with active UC to subcutaneous PF-06687234 20 mg or placebo once weekly, and participants continued intravenous background infliximab every 6 or 8 weeks, for 12 weeks.

METHODS

The primary endpoint was the proportion of participants who achieved clinical remission determined by the modified total Mayo score at week 12. Safety assessments, including adverse event (AE) reporting and laboratory abnormalities, were also primary endpoints. Secondary endpoints included the proportion of participants achieving endoscopic improvement at week 12, and exploratory endpoints included the concentration of PF-06687234 in colonic mucosal tissue from biopsies.

RESULTS

After 20 participants were randomized and treated, this study was stopped early for futility. There were no statistically significant differences between groups for any efficacy endpoint (all p > 0.05), although numerical trends towards efficacy were observed in some secondary endpoints. PF-06687234 was detected at a low concentration in only one colon tissue sample. There were no differences in AEs between the groups. The most frequently reported AE in the PF-06687234-treated group was injection site reaction.

CONCLUSION

PF-06687234 was well tolerated, but when combined with background infliximab, did not meet the primary efficacy endpoint in this cohort of participants with active UC. Efficacious PF-06687234 tissue concentrations may not have been achieved at the dose tested.

TRAIL REGISTRATION: Efficacy, safety, and tolerability of PF-06687234 as add-on therapy to infliximab in active UC subjects not in remission. https://clinicaltrials.gov/study/NCT03269695. NCT03269695.