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)

Sponsors

Lead Sponsor: Pfizer

Source 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.

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.

Overall Status Recruiting
Start Date December 20, 2017
Completion Date July 27, 2021
Primary Completion Date July 27, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of subjects in Clinical Remission Week 12
Secondary Outcome
Measure Time Frame
Proportion of subjects with endoscopic improvement Week 12
Mean change from baseline at Week 12 in Geboes histology score Baseline, Week 12
Proportion of subjects with a clinical response Week 12
Proportion of subjects with change from baseline in partial Mayo Score of 2 or less with no individual subscore >1 Weeks 2, 4, 6, 8, 12
Serum concentrations of PF 06687234 Baseline through Week 12
Incidence of the development of HAFAs and Nabs against PF 06687234. Baseline through Week 16
Enrollment 76
Condition
Intervention

Intervention Type: Drug

Intervention Name: PF-06687234

Description: SC QW

Arm Group Label: PF-06687234

Other Name: Investigational product

Intervention Type: Drug

Intervention Name: Placebo

Description: SC QW

Arm Group Label: Placebo

Other Name: PF-06687234 matched placebo

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Pfizer CT.gov Call Center Study Director Pfizer
Overall Contact

Last Name: Pfizer CT.gov Call Center

Phone: 1-800-718-1021

Email: [email protected]

Location
Facility: Status:
Dothan Surgery Center | Dothan, Alabama, 36301, United States Recruiting
Gut PC, dba Digestive Health Specialists of the Southeast | Dothan, Alabama, 36305, United States Recruiting
Gastro Florida | Clearwater, Florida, 33756, United States Not yet recruiting
Gastro Florida | Clearwater, Florida, 33762, United States Not yet recruiting
Emory Investigational Drug Services | Atlanta, Georgia, 30322, United States Terminated
Emory University Hospital | Atlanta, Georgia, 30322, United States Terminated
Emory University School of Medicine | Atlanta, Georgia, 30322, United States Terminated
The Emory Clinic | Atlanta, Georgia, 30322, United States Terminated
The University of Chicago Center for Care and Discovery -CCD (endoscopy procedures) | Chicago, Illinois, 60637, United States Not yet recruiting
The University of Chicago Center Medical Center, CCD - Investigational Drug Service Pharmacy | Chicago, Illinois, 60637, United States Not yet recruiting
The University of Chicago Medical Center (clinic address) | Chicago, Illinois, 60637, United States Not yet recruiting
The University of Chicago Medical Center Department of Pharmaceutical Services | Chicago, Illinois, 60637, United States Not yet recruiting
Chevy Chase Endoscopy Center | Chevy Chase, Maryland, 20815, United States Active, not recruiting
MGG Group Co., Inc., Chevy Chase Clinical Research | Chevy Chase, Maryland, 20815, United States Active, not recruiting
Clinical Research Institute of Michigan, LLC | Chesterfield, Michigan, 48047, United States Terminated
East Valley Endoscopy | Grand Rapids, Michigan, 49546, United States Recruiting
Eastside Endoscopy Center | Macomb, Michigan, 48044, United States Terminated
Eastside Endoscopy Center | Saint Clair Shores, Michigan, 48041, United States Terminated
Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center | Wyoming, Michigan, 49519, United States Recruiting
Allegiance Research Specialists | Wauwatosa, Wisconsin, 53226, United States Recruiting
GI Associates | Wauwatosa, Wisconsin, 53226, United States Recruiting
Concord Repatriation General Hospital | Concord, New South Wales, 2139, Australia Recruiting
Royal Brisbane and Women's Hospital | Brisbane, Queensland, 4029, Australia Not yet recruiting
Royal Adelaide Hospital | Adelaide, South Australia, 5000, Australia Not yet recruiting
Eastern Health-Box Hill Hospital | Box Hill, Victoria, 3128, Australia Recruiting
St. Vincent's Hospital, Melbourne | Fitzroy, Victoria, 3065, Australia Recruiting
The Royal Melbourne Hospital | Parkville, Victoria, 3050, Australia Recruiting
Fiona Stanley Hospital | Murdoch, Western Australia, 6150, Australia Recruiting
St John Of God Health Care Inc. Trading as St. John of God Subiaco Hospital | Subiaco, Western Australia, 6008, Australia Recruiting
University Hospitals Leuven/Department of Gastroenterology | Leuven, 3000, Belgium Not yet recruiting
CHC Montlegia | Liege, 4000, Belgium Recruiting
Universitaetsklinikum Schleswig-Holstein Campus Kiel | Kiel, 24105, Germany Recruiting
Soroka University Medical Center | Beer Sheva, 8410101, Israel Not yet recruiting
Shaare Zedek Medical Center | Jerusalem, 9103102, Israel Not yet recruiting
The Chaim Sheba Medical Center | Ramat-Gan, 5265601, Israel Recruiting
AOU Sant'Orsola - Malpighi University of Bologna | Bologna, BO, 40138, Italy Not yet recruiting
ASST Rhodense - Ospedale di Circolo di Rho | Rho, Milano, 20017, Italy Recruiting
Istituto Clinico Humanitas IRCCS, IBD center Gastroenterology Department | Rozzano, Milan, 20089, Italy Not yet recruiting
AOU Policlinico di Modena | Modena, 41124, Italy Not yet recruiting
Azienda Ospedaliera di Padova | Padova, 35128, Italy Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS | Roma, 00168, Italy Recruiting
Kyungpook National University Hospital | Daegu, Korea, 41944, Korea, Republic of Not yet recruiting
Haeundae Paik Hospital, Inje University | Busan, 48108, Korea, Republic of Not yet recruiting
Keimyung University Dongsan Hospital | Daegu, 42601, Korea, Republic of Not yet recruiting
The Catholic University of Korea, St. Vincent's Hospital | Gyeonggi-do, 16247, Korea, Republic of Recruiting
Kangbuk Samsung Hospital | Seoul, 03181, Korea, Republic of Recruiting
King Abdulaziz Medical City | Jeddah, 21423, Saudi Arabia Not yet recruiting
King Abdulaziz University Hospital | Jeddah, 22252, Saudi Arabia Recruiting
King Fahad National Guard Hospital | Riyadh, 11426, Saudi Arabia Recruiting
King Khalid University Hospital | Riyadh, 11472, Saudi Arabia Recruiting
CHC "Dr Dragisa Misovic-Dedinje" | Belgrade, 11000, Serbia Recruiting
Clinical Hospital Center Zvezdara - Clinic for Gastroenterology and Hepatology | Belgrade, 11000, Serbia Recruiting
Clinical Hospital Center Zemun | Belgrade, 11080, Serbia Not yet recruiting
Clinical Hospital Center Bezanijska Kosa | Beograd, 11080, Serbia Not yet recruiting
Hospital Universitario Virgen del Rocio | Sevilla, 41013, Spain Not yet recruiting
Bulent Ecevit Universitesi Tip Fakultesi | Kozlu, Zonguldak, 67600, Turkey Not yet recruiting
Hacettepe Universitesi Tip Fakultesi | Ankara, 06230, Turkey Not yet recruiting
Trakya Universitesi Tip Fakultesi | Edirne, 22030, Turkey Not yet recruiting
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi | Istanbul, 34093, Turkey Not yet recruiting
Mersin Universitesi Tip Fakultesi Hastanesi | Mersin, 33110, Turkey Recruiting
Bulent Ecevit Universitesi Tip Fakultesi | Zonguldak, 67600, Turkey Not yet recruiting
Location Countries

Australia

Belgium

Germany

Israel

Italy

Korea, Republic of

Saudi Arabia

Serbia

Spain

Turkey

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: PF-06687234

Type: Experimental

Description: PF-06687234 subcutaneous (SC) weekly (QW) x 12 doses

Label: Placebo

Type: Placebo Comparator

Description: PF-06687234 matched Placebo SC QW x 12 doses

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov