Clinical trial NCT03269695: Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-09-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants in Modified Clinical Remission at Week 12 (Traditional Endoscopic Subscore <=1, Observed Cases)
timeFrame: Week 12
measure: Percentage of Participants in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Treatment Failure Approach)
timeFrame: Week 12
measure: Percentage of Participants in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Observed Cases)
timeFrame: Week 12
measure: Percentage of Participants in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Treatment Failure Approach)
timeFrame: Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs; All Causalities)
timeFrame: Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)
measure: Number of Participants With Treatment-Emergent AEs (Treatment Related)
timeFrame: Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)
measure: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
timeFrame: From baseline through Week 16
measure: Number of Participants With Categorical Vital Signs
timeFrame: From baseline through Week 16
measure: Number of Participants With Categorical Electrocardiogram (ECG) Data
timeFrame: From baseline through Week 16
Secondary outcomes:
measure: Percentage of Participants With Endoscopic Improvement at Week 12 ( Observed Cases)
timeFrame: Week 12
measure: Percentage of Participants With Endoscopic Improvement at Week 12 ( Treatment Failure Approach)
timeFrame: Week 12
measure: Percentage of Participants Achieving Geboes Index Remission at Week 12 (Observed Cases)
timeFrame: Week 12
measure: Change From Baseline in Robart's Histology Index at Week 12 (Observed Cases)
timeFrame: Week 12
measure: Percentage of Participants With a Clinical Response at Week 12 (Observed Cases)
timeFrame: Week 12
measure: Percentage of Participants With a Clinical Response at Week 12 (Treatment Failure Approach)
timeFrame: Week 12
measure: Percentage of Participants With Change From Baseline in Derived Partial Mayo Score of <=2 With no Individual Subscore >1 at Weeks 2, 4, 8 and 12 (Observed Cases)
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Serum Concentrations of PF-06687234 20 mg
timeFrame: Prior to dosing on Day 1 and at Weeks 1, 3, 7, 11, 12 (168 hours post dose) and 16
measure: Percentage of Participants With the Development of Human Anti-Fusion Antibodies (HAFAs) and Neutralizing Antibodies (NAbs) Against PF-06687234
timeFrame: At screening, Day 1, Weeks 3, 7, 11, 12 and 16 (prior to dosing)
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Dothan Surgery Center
state: Alabama
city: Dothan
country: United States
facility: Gut PC, dba Digestive Health Specialists of the Southeast
state: Alabama
city: Atlanta
country: United States
facility: Emory Investigational Drug Services
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chevy Chase
country: United States
facility: Chevy Chase Endoscopy Center
state: Maryland
city: Chevy Chase
country: United States
facility: MGG Group Co., Inc., Chevy Chase Clinical Research
state: Maryland
city: Chesterfield
country: United States
facility: Clinical Research Institute of Michigan, LLC
state: Michigan
city: Grand Rapids
country: United States
facility: East Valley Endoscopy
state: Michigan
city: Macomb
country: United States
facility: Eastside Endoscopy Center
state: Michigan
city: Saint Clair Shores
country: United States
facility: Eastside Endoscopy Center
state: Michigan
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center
state: Michigan
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists
state: Wisconsin
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Eastern Health-Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital, Melbourne
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St John Of God Health Care Inc. Trading as St. John of God Subiaco Hospital
state: Western Australia
city: Liege
country: Belgium
facility: CHC Montlegia
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Rho
country: Italy
facility: ASST Rhodense - Ospedale di Circolo di Rho
state: Milano
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz University Hospital
city: Riyadh
country: Saudi Arabia
facility: King Abdullah International Medical Research Center
city: Riyadh
country: Saudi Arabia
facility: King Khalid University Hospital
city: Belgrade
country: Serbia
facility: CHC "Dr Dragisa Misovic-Dedinje"
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara - Clinic for Gastroenterology and Hepatology
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Hastanesi
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: