Vibrato Study B7981005: A Phase 2B, Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Dose Ranging Study of Oral PF-06651600 and PF-06700841 as Induction and Chronic Therapy in Patients with Moderate to Severe Ulcerative Colitis

Study Description

• This is a Phase 2b randomized double-blind placebo controlled study in patients with moderate to severe UC.  The study will be conducted at approximately 198 centers from 24 countries, and is expected to enroll approximately 360 patients.
• Enrolled patients will receive either PF-06651600, PF-06700841 or placebo.
• Participants who are enrolled in the PF-06651600 group will either receive 20, 70 or 200 mg of study drug daily or matching placebo. 
• Participants who are enrolled in to the PF-06700841 group you will receive either 10, 30, or 60 mg daily of the study drug or a matching placebo.
• Following the 8 week induction period of the study, all participants, including those on placebo, will be re-assigned to the chronic therapy period (24 weeks) of the study.
• Participants originally in the group receiving PF-06651600 will either receive 50 mg of the study drug or matching placebo.
• Participants originally in the group receiving PF-06700841 will either receive 30 mg of the study drug or placebo.

Description of Treatment or Intervention (Mechanism of Action)

• PF-06651600 and PF-06700841 are investigational drugs. PF-06651600 is in a class called JAK3 inhibitors, which could be helpful in treating UC.  PF-06700841 is in a class called TYK2 and JAK1 which together could be helpful in treating UC.  PF-06651600 and PF-06700841 may decrease the inflammation and ulceration of Ulcerative Colitis by inhibiting production of cytokines (small proteins) which are thought to be key drivers of the disease.
• PF-06651600, PF-06700841 or placebo will be taken as oral tablets.

Patient Participation Requirements

• Eligible patients will have at least 11 site visits.  The duration of participation of eligible patients will be approximately 10 months (42 weeks).
• Written informed consent must be obtained prior to performance of any protocol-specific procedures.  Patients will be screened to confirm that they meet all inclusion/exclusion criteria for the study.
• Screening procedures include: complete medical history, medication history, 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.  You will have a chest X-ray, if you have not had one in the last 12 weeks.  A screening endoscopy (flexible sigmoidoscopy or colonoscopy) will be performed. 
• During the treatment period, blood and stool samples will be collected periodically for safety, effectiveness, and exploratory assessments. An additional endoscopy will be performed at week 8 and at week 32, after which participants will enter the follow-up period.
• Participants will be required to keep an electronic diary beginning with the first screening visit and ending at the final study visit. Participants will record information daily on their stool frequency and rectal bleeding.  There will be quality of life questionnaires to complete throughout the study.

Possible Risks & Side Effects

• PF-06651600 (Study Drug): may cause diarrhea, headache and erythema.  May cause rashes or infections.
• PF-06700841 (Study Drug): may cause headache, constipation.  May cause infections.
• At this time, the effects of PF-06700841 on male and female fertility, and pregnancy in humans, and effects on fetus or a nursing child are not known.   For this reason strict use of birth control must be followed.
• Both PF-06651600 and PF-06700841 are investigational, so there may be other risks that are unknown.

Placebo Risk:

• Certain research participants in this research study will receive a placebo.  Taking a placebo may be similar to not taking any medication.  If you are one of the people who receive a placebo, your UC may stay the same or get worse, or your UC may suddenly get better just as it may have done without additional treatment.

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.
• Hearing test (audiogram): no risks associated with having an audiogram.
• 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.
• Endoscopy (Flexible Sigmoidoscopy and Colonoscopy):  Complications of this procedure 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.