A PHASE 2A, MULTICENTER, SINGLE ARM, OPEN-LABEL, TWO-STAGE, STUDY TO EVALUATE THE EFFICACY, SAFETY,TOLERABILITY AND PHARMACOKINETICS OF PF-06480605 IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS

Phase 2

Completed

• Conditions: inflammation of the intestine; inflammatory bowel disease (IBD); 10017969

• Registration Number: NL-OMON47159
• Lead Sponsor: Pfizer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2024-02-28

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:;1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.;2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.;3. Male and/or female subjects between *18 and *75 years of age at the time of informed consent.;4. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit (or 98 days after the last dose of IP).;Women of childbearing potential (WOCBP) will be eligible for this study provided these women use two highly effective
methods of contraception throughout the study and until the Week 26 visit (or 98 days after the last dose of IP), as outlined in Section 4.3. ;Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):;* Have undergone a documented hysterectomy and/or bilateral oophorectomy;;* Have medically confirmed ovarian failure; or;Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state.;5. A diagnosis of UC for *4 months. A biopsy report must be available to confirm the histological diagnosis in the subject*s source documentation. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, and pancolitis) based upon prior endoscopy must also be available in source documentation.;6. Subjects with moderate to severe active UC as defined (via screening colonoscopy) by a total Mayo score of *6, with a rectal bleeding subscore of *1 and an endoscopic subscore of *2 on the Mayo.;7. Active disease beyond the rectum (>15 cm of active disease at the screening colonoscopy).;8. Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC:;* Steroids;;* Immunosuppressants (AZA [azathioprine], 6-MP, or MTX [methotrexate]);;* Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab);;* Anti-integrin inhibitors (eg, vedolizumab).;For subjects in The Netherlands: Subjects must have inadequate response to, loss of response to, or intolerance to at least one biological therapy, such as an anti-TNF inhibitor.;Note: The information below is provided as guidance. Local standards of care, as well as investigator assessment should be considered.;Inadequate response to, loss of response to, or intolerance to corticosteroid treatment is defined as one or more of the following:;* Steroid refractory: persistent symptoms of active disease despite treatment with at least one 4-week induction regimen that included a dose of *30 mg prednisone (oral) daily for at least 2 weeks or IV for at least 1 week within the previous
5 years;;* Steroid dependent: two failed attempts to taper steroids below a dose equivalent to 10 mg prednisone (oral) daily;;* Steroid intolerant: history of intolerance to corticosteroids (including but not limited to Cushing*s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection) within the previous 5 years.;I

Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the study:;1. Subjects with a diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or CD. Subjects with clinical findings suggestive of CD (eg, fistulae, granulomas on biopsy) are also excluded.;2. Subjects with an imminent need for surgery or with elective surgery scheduled to occur during the study.;3. Subjects with colonic dysplasia or neoplasia.;4. Subjects with toxic megacolon.;5. Subjects with primary sclerosing cholangitis.;6. Subjects with known colonic stricture.;7. Subjects with history of colonic or small bowel stoma.;8. Subjects with a history of colonic or small bowel obstruction or resection.;9. Abnormal findings on the chest x-ray film performed routinely before initiating a new biologic therapy, such as presence of tuberculosis (TB), general infections, heart failure, or malignancy. Chest x-ray examination may be performed up to 12 weeks prior to screening. Documentation of the official reading must be located and available in the source documentation.;10. Any current evidence of untreated latent or active TB infection, evidence of prior or currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB. Subjects who have a positive Mantoux (PPD)
tuberculin skin test or a positive Interferon Gamma Release Assay (IGRA to be tested
at the site*s local lab where feasible) during screening or within 12 weeks prior to randomization. The following are acceptable assays: QuantiFERON*-TB Gold test (QFT-G), QuantiFERON*-TB Gold In-Tube test (QFT-GIT) and T-SPOT*-TB test during screening or within 12 weeks prior to screening.;* A positive Mantoux tuberculin skin test is defined as *5 mm of induration (or as defined by country specific or local standards) at 48-72 hours without consideration of prior Bacillus Calmette-Guerin (BCG) vaccination. Documentation of the dose and product used for the Mantoux tuberculin test as well as the official test reading must be obtained and available in the subject*s source documentation.;* An IGRA is preferred for subjects with a prior BCG vaccination (to be tested by a site*s local lab where feasible), but may be used for any subject. Documentation of IGRA product used and the test result must be in the subject*s source documentation.;* If results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. A positive test on repeat is exclusionary.;* Subjects with repeat indeterminate IGRA results may be enrolled after consultation with pulmonary or infectious disease specialist that determines low risk of infection (ie, subject would be acceptable for immunosuppressant
(eg, anti-TNF) treatment without additional action).;* Subjects with adequately treated latent tuberculosis infection may be enrolled regardless of Mantoux or IGRA results.;11. Presence of active enteric infections (positive stool culture and sensitivity). The presence of Clostridium difficile or pseudomembranous colitis. Known active invasive fungal infections such as histoplasmosis or parasitic infections. Subjects with clinically significant underlying disease that could predispose the subjects to infections. A history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before Day 1. Pyoderma gangreno

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoints<br /><br>* Safety and tolerability of PF-06480605: TEAEs, withdrawal due to AEs, and<br /><br>SAEs will be reported.<br /><br><br /><br>* Endoscopic improvement at Week 14 (defined as a Mayo endoscopic subscore of 0<br /><br>or 1, and without friability).</p><br>