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

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ClinicalTrials.gov Identifier: NCT03269695
Recruitment Status : Recruiting
First Posted : September 1, 2017
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: PF-06687234 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : February 26, 2020
Estimated Study Completion Date : February 26, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Arm Intervention/treatment
Experimental: PF-06687234
PF-06687234 subcutaneous (SC) weekly (QW) x 12 doses
Drug: PF-06687234
SC QW

Placebo Comparator: Placebo
PF-06687234 Placebo SC QW x 12 doses
Drug: PF-06687234
SC QW




Primary Outcome Measures :
  1. Proportion of subjects in Clinical Remission [ Time Frame: Week 12 ]
    Clinical remission defined by a modified Mayo Score with an endoscopic subscore less than or equal to 1, stool frequency subscore less than or equal to 1 and rectal bleeding subscore = 0


Secondary Outcome Measures :
  1. Proportion of subjects with endoscopic improvement [ Time Frame: Week 12 ]
    Endoscopic improvement defined as decrease of 1 point in Mayo endoscopy score or an absolute endoscopy score of 1 or less.

  2. Mean change from baseline at Week 12 in Geboes histology score [ Time Frame: Baseline, Week 12 ]
    Mean change from baseline at Week 12 in Geboes score.

  3. Proportion of subjects with a clinical response [ Time Frame: Week 12 ]
    Clinical response defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one point decrease or absolute score of 0 or 1 in rectal bleeding subscore.

  4. Proportion of subjects with change from baseline in partial Mayo Score of 2 or less with no individual subscore >1 [ Time Frame: Weeks 2, 4, 6, 8, 12 ]
    Proportion of subjects with partial Mayo score <=2 with no individual subscore of > 1 at Week 2, 4, 6, 8 and 12

  5. Serum concentrations of PF 06687234 [ Time Frame: Baseline through Week 12 ]
    Measure serum concentration of PF-06687234 at baseline, Week 1, 3, 7, 11, 12, and 16

  6. Incidence of the development of HAFAs and Nabs against PF 06687234. [ Time Frame: Baseline through Week 16 ]
    Measure HAFA and neutralizing antibody against IL10 at screen, baseline, Week 3, 7, 11, 12, and 16



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269695


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 48 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03269695     History of Changes
Other Study ID Numbers: B7581002
2017-002108-28 ( EudraCT Number )
BUILD UC ( Other Identifier: Alias Study Number )
First Posted: September 1, 2017    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Infliximab
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents