Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission.

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06687234 AS ADD-ON THERAPY TO INFLIXIMAB IN ACTIVE ULCERATIVE COLITIS SUBJECTS WHO ARE NOT IN REMISSION (BUILD UC)

The purpose of this study is to determine if PF-06687234 is effective and safe as add-on therapy to infliximab in subjects with active ulcerative colitis who are not in remission.

This is a Phase 2a, double-blind, placebo-controlled, parallel group study in subjects with active ulcerative colitis and a non-remission (partial) response to infliximab. All enrolled subjects must have been on infliximab for a minimum of 14 weeks with last dose 8 weeks prior to the date of randomization. Subjects will be randomly assigned to 1 of 2 treatment arms (PF-06687234 or placebo) administered subcutaneously every week for a total of 12 doses. Blood, stool and tissue samples will be collected at various time points throughout the study to evaluate efficacy, safety, tolerability, pharmacokinetics and immunogenicity. Duration of participation for subjects will be approximately 6 months.

Inclusion Criteria:

• Male and/or female subjects 18 years to 75 years of age and weight > 40 kg at the time of informed consent.
• A diagnosis of active UC (histologic) for 4 months.
• Subjects with active UC as defined by (via screening endoscopy) a total Mayo Score of 4 or more but 9 or less and an endoscopic subscore of 2.or more.
• UC extending at least 15 cm proximal to the anal verge at the time of the screening endoscopy.
• Must be on a stable dose 5-10 mg/kg of Remicade, Inflectra, or Remsima for a minimum of 14 weeks with no anticipation of need for change in infliximab treatment regimen throughout the study
• Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two methods of contraception (at least one of which is considered as highly effective) throughout the study and until the Week 16 visit

Exclusion Criteria:

• 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 need for surgery or with major elective surgery scheduled 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.

• Subjects with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia.

• Subjects who require infliximab dosing interval other than every 6 weeks or every 8 weeks.

• Subjects displaying clinical signs of fulminant colitis or toxic megacolon, with primary sclerosing cholangitis, known colonic stricture, history of colonic, small bowel obstruction or resection, with history of or current colonic or small bowel stoma.

• Cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or history of chronic anemia.

• Presence of active enteric infection.

• Known history of human immunodeficiency virus (HIV) based on documented history with positive serological test, or positive HIV serologic test.

• Presence of transplanted organ.

• Anticipated need for any live vaccine.

• Class III or Class IV heart failure.

• Acute coronary syndrome and any history of cerebrovascular disease.

• Subjects with current, or a history of QT prolongation.

• Subjects receiving the following therapies within the designated time period:

  • >9 mg/day of oral budesonide or >20 mg/day of prednisone or equivalent within 2 weeks prior to baseline.
  • IV, IM or topical (rectal) treatment of 5-ASA or corticosteroid enemas within 2 weeks prior to baseline.
  • Anti integrin inhibitors within 14 weeks prior to baseline.
  • Any use of natalizumab.
  • Interferon therapy within 8 weeks prior to baseline.
  • Prior treatment with lymphocyte depleting therapies and alkylating agents.
  • Received selective B lymphocyte depleting agents within 1 year prior to baseline.
  • Receiving leukocyte apheresis, granulocyte apheresis, or plasma exchange within 6 months of baseline.
  • JAK inhibitors within 3 months prior to baseline.
  • Any investigational procedures(s) or product(s)30 days prior to baseline.

• History of sensitivity to heparin or heparin induced thrombocytopenia

• Known history of hypersensitivity, intolerance, or allergic reaction to PF-06687234 or any constituent of the IP.