PF-06687234 is an agonist, an antibody fragment fused to an immunoregulatory cytokine, called IL-10.2-4

As a dual-functioning therapy, the antibody portion binds to a spliced variant of fibronectin that is increased at sites of inflammation. There is abundant expression at accessible sites of tissue remodeling, while being undetectable in most normal human tissues.2

PF-06687234 is under investigation in subjects with active rheumatoid arthritis receiving methotrexate and adults with active ulcerative colitis and a partial response to infliximab.5,6

aPfizer has an exclusive license from Philogen to develop this compound.7

IL-10 PATHWAY

IL-10 is an anti-inflammatory cytokine that may help reduce inflammation in
multiple diseases, such as rheumatoid arthritis and ulcerative colitis.2,10

Figure adapted from Fioranelli M, Grazia RM. J Integr Cardiol. 2014;1(1):2-6.

  • Anti-inflammatory cytokines, such as IL-10, help prevent inflammatory and autoimmune conditions11
  • The binding of IL-10 to its receptor triggers a signaling pathway that ultimately limits the production of proinflammatory cytokines and chemokines, such as IL-1, IL-6, and TNF-α8,12
  • IL-10 plays a potential role in human diseases:
    • In rheumatoid arthritis, the addition of IL-10 to synovial membrane cultures can decrease IL-1β and TNF-α expression. Similarly, blocking endogenous IL-10 can cause a 2- to 3-fold increase in the expression of these proinflammatory cytokines13
    • In ulcerative colitis, the IL-10 gene has been identified as a susceptibility locus, with certain genetic variants being associated with the disease14
  • Activating the IL-10 pathway has shown promise as a therapeutic strategy in preclinical mouse models2,15

Now enrolling in ulcerative colitis

For adults with diagnosed active ulcerative colitis who
are not in remission with infliximab treatment5

PF-06687234 (Dekavil) is an investigational IL-10 agonist.1,a

IL-10 is an immunoregulator in the intestinal tract and thought to counteract inflammatory immune responses.9

This is a phase 2a, randomized, double-blind, placebo-controlled, parallel-group study of PF-06687234 as add-on therapy to infliximab in subjects with active ulcerative colitis and a nonremission (partial) response to infliximab.5

Planned countries for recruitment include: Australia, Belgium, Germany, Israel, Italy, Saudi Arabia, Serbia, South Korea, Spain, and the United States.5

aPfizer has an exclusive license to develop this compound.7

VIEW STUDY DESIGN5

VIEW ENDPOINTS5,16

PRIMARY ENDPOINT5

  • Proportion of subjects in clinical remissionb at 12 weeks

bClinical remission defined by a modified Mayo Score with an endoscopic subscore ≤1, stool frequency subscore ≤1, and rectal bleeding subscore of 0.

KEY SELECTED SECONDARY ENDPOINTS5

  • Proportion of subjects with endoscopic improvementc at 12 weeks
  • Proportion of subjects with a clinical responsed at 12 weeks
  • Mean change from baseline at week 12 in Geboes histology score

bClinical remission defined by a modified Mayo Score with an endoscopic subscore ≤1, stool frequency subscore ≤1, and rectal bleeding subscore=0.
cEndoscopic improvement defined as a decrease of 1 point in Mayo Endoscopy Score or an absolute endoscopy score of ≤1.
dClinical response defined as a decrease from baseline of ≥3 points in total Mayo Score with ≥30% change, accompanied by ≥1 point decrease or absolute score of 0 or 1 in rectal bleeding subscore.

VIEW ELIGIBILITY CRITERIA

KEY SELECTED INCLUSION CRITERIA5

  • 18 to 75 years of age at the time of informed consent
  • A diagnosis of active ulcerative colitis (histologic) for ≥4 months
  • Subjects with active ulcerative colitis as defined by (via screening endoscopy) a total Mayo Score ≥4 but ≤9 and an endoscopic subscore ≥2
  • Must be on a stable dose 5 mg/kg to 10 mg/kg of infliximab (biosimilar versions are acceptable) for a minimum of 14weeks with no anticipation of need for dose adjustment throughout the study
  • Male subjects able to father children and female subjects of childbearing potential must agree to use 2 methods of contraception (at least one of which is considered as highly effective) throughout the study and until the week 16 visit

KEY SELECTED EXCLUSION CRITERIA5

  • Subjects with a diagnosis or documented history of total colectomy and/or pouchitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or clinical findings suggestive of Crohn’s disease
  • Subjects considered in imminent need for surgery or with major elective surgery scheduled to occur during the study
  • Subjects with extensive colitis for at least 8 years who have not had a colonoscopy with surveillance biopsies within 2 years prior to baseline

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