General Information:

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 Patients Who Are Not In Remission (BUILD UC)

Title of Study

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 Patients Who Are Not In Remission (BUILD UC)

Study Objective

The primary objectives of this study are to determine if an investigational drug called PF-06687234, is safe, tolerable, and effective as an add-on therapy to Infliximab in the treatment of patients with active ulcerative colitis.

Phase of study

2a

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Eligibility:

Age

Adult (18+)

Gender

Female, Male

Disease Type

Ulcerative Colitis

Severity

Mild, Moderate

Eligibility Criteria

The inclusion criteria for study participation are noted as follows:

  • Evidence of a personally signed and dated informed consent document.
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
  • Male and/or female patients 18 - 75 years of age at the time of informed consent
  • Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the entire study and until the Week 16 visit (or 28 days after the last dose of IP).
  • A diagnosis of active UC (histologic) for >/-4 months.
  • Patients with active UC as defined by (via screening endoscopy) a total Mayo Score of >/-5 but/-2.
  • UC extending at least 25 cm proximal to the anal verge at the time of the screening endoscopy. Only a portion of the 25 cm of involved colon must be graded with Mayo endoscopic subscore of 2.
  • Patients currently receiving stable doses of UC medication: Oral 5-aminosalicylic acid derivative (5-ASA) or sulfasalazine stable dose for at least 4 weeks prior to baseline, Oral corticosteriods (prednisone equivalent up to 20 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline, 6 mp, azathioprine (AZA) (25 mg/kg), or MTX stable dose for 8 weeks prior to baseline.

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Study Details:

Study Description

  • The duration of participation for eligible patients will be approximately 26 weeks. This will include a 4-week screening, a 12-week treatment, and a 10-week follow-up period which will include a telephone contact conducted 6-weeks after the on-site follow-up visit.  During the 12-week treatment period patients will visit the clinic every week for SC study drug PF-06687324 or placebo for a total of 12 visits. In addition, all patients enrolled will receive their IV infliximab therapy on Day 1, Week 8 visit and at the final on-site visit at Week 16.
  • Patients with adverse events as a result of positive ADA/NAbs may be requested to return for additional follow-up for up to 3 months after the Week 22 telephone study visit.
  • Patients will be screened to confirm that they have met all inclusion/exclusion criteria for the study and a screening colonoscopy or sigmoidoscopy will be performed. Written informed consent must be obtained prior to performance of any protocol-specific procedures. Screening procedures include: complete medical history, medication history, vital signs, chest X-ray, ECG, and prior treatment for ulcerative colitis. A complete physical examination will be performed including collection of blood, urine, and stool samples. Women of childbearing potential will be tested for pregnancy and will need to adhere to strict contraception requirements throughout the study.  During the treatment period, blood and stool samples will be collected periodically for safety, efficacy, and exploratory assessments. A final colonoscopy or sigmoidoscopy will be performed at week 12 and patients will enter the follow-up period at this time.
  • Patients will be required to keep an electronic diary beginning with the first screening visit and ending at the final study visit.  Patients will record information daily on their stool frequency and rectal bleeding. 

Description of Treatment or Intervention (Mechanism of Action)

  • Mechanism of Action: Ulcerative colitis is a chronic disease which causes inflammation of the intestines.  The inflammation of the intestines is a factor responsible for many of the symptoms you may experience.  Inflammation means that excess white blood cells enter healthy tissue and cause disease. 
  • The name of the study drug being investigated is called PF-06687234. PF-06687234 is made of two connecting proteins (F8 and IL10). The F8 protein seeks out and attaches to areas of inflammation (for example the colon, in UC). The IL10 protein works to “calm down” the immune system in inflamed areas such as the colon. You may be taking a medication such as Infliximab for your Ulcerative Colitis but you still have symptoms.  When PF-06687234 is added to Infliximab, it may further decrease the inflammation of Ulcerative Colits and thus provide relief of your symptoms.
  • Study Design:  This is a Phase 2A, randomized, double-blind, placebo-controlled, parallel group, multicenter study in patients with active UC and a non-remission (partial) response to Infliximab.  Each patient will be randomly assigned to 1 of 2 treatment arms (1 active;1 placebo) with approximately 68 patients in total (34 patients per arm).  A total of 50 sites from 10 countries are planned to participate in this study. 
  • Patients will receive PF-06687234 study drug subcutanteously (SC) once a week for a total of 12 doses.  In addition, all patients will be provided with 3 doses of intravenous (IV) infliximab therapy.  Patients will be evaluated by colonoscopy or sigmoidoscopy during screening to determine eligibility and will need to meet all inclusion/exclusion criteria to participate in the full study. The study will include a screening period of up to 4 weeks, a 14 week induction period (treatment of 12 doses of SC PF-06687234 study drug once a week), a final colonoscopy or sigmoidoscopy once PF-0667234 treatment is complete at week 14, and a 10 week follow-up period.  Patients will receive their IV infliximab therapy on Day 1, Week 8 and at the Week 16 follow-up visit.  A telephone follow-up visit will be done 6 weeks following Week 16 to evaluate your general health. In addition to receiving study drug, study procedures will include periodic blood, stool, and urine samples for safety, efficacy, immunogenicity, (which is the potential for your body's immune system to form antibodies to the drug) and exploratory analyses.  Tissue samples will be collected during the colonoscopy and sigmoidoscopy procedures for additional analyses. These exploratory analyses will examine potential DNA, RNA, protein, and microbiome biomarkers that will help us understand how the drug works, what patients might best respond to this therapy, and more about the basic mechanisms of inflammatory bowel disease. This critical part of the study could speed later clinical development of PF-06687234 and other future therapies.

Patient Participation Requirements

  • The duration of participation for eligible patients will be approximately 26 weeks. This will include a 4-week screening, a 12-week treatment, and a 10-week follow-up period which will include a telephone contact conducted 6-weeks after the on-site follow-up visit.  During the 12-week treatment period patients will visit the clinic every week for SC study drug PF-06687324 or placebo for a total of 12 visits. In addition, all patients enrolled will receive their IV infliximab therapy on Day 1, Week 8 visit and at the final on-site visit at Week 16.
  • Patients with adverse events as a result of positive ADA/NAbs may be requested to return for additional follow-up for up to 3 months after the Week 22 telephone study visit.
  • Patients will be screened to confirm that they have met all inclusion/exclusion criteria for the study and a screening colonoscopy or sigmoidoscopy will be performed. Written informed consent must be obtained prior to performance of any protocol-specific procedures. Screening procedures include: complete medical history, medication history, vital signs, chest X-ray, ECG, and prior treatment for ulcerative colitis. A complete physical examination will be performed including collection of blood, urine, and stool samples. Women of childbearing potential will be tested for pregnancy and will need to adhere to strict contraception requirements throughout the study.  During the treatment period, blood and stool samples will be collected periodically for safety, efficacy, and exploratory assessments. A final colonoscopy or sigmoidoscopy will be performed at week 12 and patients will enter the follow-up period at this time.
  • Patients will be required to keep an electronic diary beginning with the first screening visit and ending at the final study visit.  Patients will record information daily on their stool frequency and rectal bleeding. 

Possible Risks & Side Effects

Risks related to study drug PF-06687234 may include: 

  • Headache.
  • Rash.
  • A decrease in red-blood cells or platelets.
  • May cause a rare, life-threatening, overactive immune system reaction in the blood, lungs, kidneys and other organs.
  • Injection site reaction (redness, itching or pain at the location where study drug was injected).
  • May cause the body to form antibodies to the drug, causing an allergic reaction.
  • The effects of the study drug on male and female fertility, a pregnancy, a fetus, or a nursing child are not known. For these reasons, strict use of birth control must be followed per protocol.
  • Since PF-06687234 is investigational, there may be other risks that are unknown. 

Risks related to study procedures:

  • Blood draws: A blood draw may cause faintness, inflammation of the vein, pain, bruising, or bleeding at the site of puncture. 
  • ECG:  The risks from an ECG can include skin irritation and a rash from the gel that is used or from wearing or removing the patches.
  • Chest X-ray: The amount of radiation from a chest x-ray will be about 0.1 millisievert (mSv).  There is no significant risk from this total amount of radiation.
  • Colonoscopy and Sigmoidoscopy:  Complications are very uncommon and may include bleeding and perforation (tear or hole in the bowel). 
  • Tissue biopsies: Small pinches of tissue from the intestine will be taken during endoscopy and may cause potential minor bleeding. You will not feel any pain from this.

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Contact Information:

Site Locations

Clinical Research Institute of MichiganSuite 206, 30795 23 Mile RoadChesterfield, MI, 48047
Joe Palmer586-598-3329jpalmer@researchmi.com
Louisiana Research Center1800 E. 70th StreetShreveport, LA, 71105
Tricia Walker318-213-3454 twalker@gis.md
Washington University School of Medicine660 South Euclid Avenue, Campus Box 8124St. Louis, MO , 63110
Susan Jones314-747-3670 jonessusan@wustl.edu
Emory University School of MedicineBuilding B Suite 1200, 1365 Clifton RoadAtlanta, GA , 30322
404-778-5000tdhere@emory.edu
Gastroenterology Associates of TidewaterSuite 200, 112 Gainsborough SquareChesapeake, VA , 23320
Crystal Beaber757-842-6009CBeaber@gatgi.com
Gastrointestinal BiosciencesSuite 1206, 2080 Century Park EastLos Angeles, CA, 90067
Raymond Ochoa 310-282-0525rayo59@prodigy.net
Capital Digestive Care5550 Friendship Boulevard, Suite T-90Chevy Chase, MD , 20815
Shalee Blakeney301-652-5520Shalee.Blakeney@capitaldigestivecare.com
Gastroenterology Associates of Western Michigan d.b.a West Michigan Clinical Research Center2093 Health Dr. Ste 201Wyoming, MI 29519
Andrea Krautwurst616-328-5344 aantvelink@gastro-assoc-wm.com
The University of Chicago Medical Center5841 South Maryland Avenue MC 4076Chicago, IL 60637
Kristi Kearney 773-834-7414 kkearney@medicine.bsd.uchicago.edu
Digestive Health Specialists of the SE480 Honeysuckle RoadDothan, AL 36305
Dawn Barnes334-836-0096dbarnes@dothangi.com
NYU Langone Long Island Clinical Research Associates1000 Northern Boulevard Suite 160Great Neck, NY 11021
Susan Eugene 516-466-1051 x330susan.eugene@nyumc.org

Global Study

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