Study to evaluate the effectiveness of oral PF-06651600 and PF-06700841 in subjects with moderate to severe ulcerative colitis, a disease characterized by continuous inflammation that is localized to the colo
- Conditions
- Moderate to severe Ulcerative Colitis (UC)MedDRA version: 20.0Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2016-003708-29-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 317
1. Male and/or female subjects =18 years to =70 years of age at the time of informed consent.
2. A diagnosis (endoscopic or radiographic, plus histological) of UC for =4 months prior to entry into the study. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, or pancolitis) based upon prior endoscopy must also be available in the source documentation.
3. Subjects with moderate to severe active UC as defined (via screening endoscopy) by a total Mayo score of =6, with a rectal bleeding subscore of =1 and an endoscopic subscore of =2. Endoscopy (colonoscopy or flexible sigmoidoscopy) must be performed within 10 days of baseline, preferably 5 to 7 days prior to baseline to allow calculation of total Mayo score. The endoscopic subscore assessed by the Central Reader must be available at the baseline visit. The assessment by the Central Reader will be used to derive the total Mayo score to determine study eligibility.
4. Active disease beyond the rectum (>15 cm of active disease from the anal verge at the screening endoscopy).
5. Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC:
• Steroids;
• Immunosuppressants (azathioprine [AZA], 6-MP, or methotrexate [MTX]);
• Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab);
• Anti-integrin inhibitors (eg, vedolizumab).
Please refer to the protocol for further guidance on the definition of inadequate response to, loss of response to and intolerance of corticosteroid treatment, immunosuppressant treatment, anti-TNF inhibitors and anti-integrin inhibitors.
6. Subjects currently receiving the following treatment for UC are eligible providing they have been on stable doses as described below:
• Oral 5-ASA or sulfasalazine stable dose for at least 4 weeks prior to baseline. If oral 5-ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to total Mayo score screening procedures.
• Oral corticosteroids (prednisone up to 25 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to total Mayo score screening procedures. Decreases in steroid use due to adverse events are allowed.
7. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
9. Female subjects of childbearing potential must test negative for pregnancy at screening visit and baseline visit.
10. Female subjects considered to be of non-childbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbear
1. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use 2 effective methods of contraception as outlined in the protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or clinical findings suggestive of Crohn’s disease (eg, fistulae, granulomas on biopsy).
3. Subjects considered in imminent need for surgery or with elective surgery scheduled to occur during the study.
4. Subjects with a history of bowel surgery within 6 months prior to baseline.
5. Subjects with colonic dysplasia or neoplasia.
6. Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
7. Subjects with primary sclerosing cholangitis.
8. Subjects with known colonic stricture.
9. Subjects with history of colonic or small bowel stoma.
10. Subjects with a history of colonic or small bowel obstruction or resection.
11. Subjects with evidence of colonic adenomas or dysplasia. However, subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and the subjects are free of polyps at baseline.
12. Subjects who meet either of the 2 criteria below are considered at risk for colorectal cancer and must have a colonoscopy. Colonoscopy report and pathology report (if biopsies obtained) must be available in the source document:
•If the subject is =50 years of age, a colonoscopy within 10 years of screening visit is required to exclude adenomatous polyps. Subjects whose adenomas have been completely excised must have had repeat surveillance colonoscopy confirming no additional adenomatous polyps as per local guidelines to be eligible.
•If the subject has had extensive (ie, greater than left sided) colitis for =8 years or disease limited to left side of colon (ie, distal to splenic flexure) for =10 years, regardless of age, a colonoscopy within 1 year of screening visit is required to survey for dysplasia. Subjects with dysplasia or cancer identified on biopsies will be excluded.
13. Subjects receiving the following therapies within the time period described below or expected to receive any of these therapies during the study period:
•>9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
•IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
•Anti-TNF inhibitors (or biosimilars thereof) as described below:
- Infliximab within 8 weeks prior to baseline;
- Adalimumab within 8 weeks prior to baseline;
- Golimumab within 8 weeks prior to baseline.
•Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline.
•Interferon therapy within 8 weeks prior to baseline.
•Subjects with prior treatment with lymphocyte-depleting agents/therapies (eg, CamPath® [alemtuzumab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc).
•Subjects who have received rituximab or other selective B lymphocyte-depleting agents within 1 year prior to baseline.
•Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method