Moderate to severe Ulcerative Colitis Ulcerative Colitis
Conditions
Interventions
The study consists of a screening period up to 6 weeks and a 12-week treatment period. After the screening period, eligible subjects will be randomly assigned to receive 1 of 3 treatments (25 mg SHP64
for subjects who achieve clinical response) or a long-term safety extension (LTS) study (SHP647-304
for subjects who do not achieve a clinical response). Subjects who withdraw early from the 12-week treatment period or who do not wish to enter the maintenance study (SHP647-303) or LTS study (SHP647-
randomization ratio: 2:2:1 for SHP647 25mg, 75mg and Placebo respectively
Sponsors
Shire Human Genetic Therapies, Inc. ("Shire")
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. 2. Subjects must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. 3. Subjects must be between =16 and =80 years of age at the time of the signing of the informed consent/assent form (for Lebanon must be = 18 and =80 years of age). NOTE: Subjects <18 years of age must weigh =40 kg and must have body mass index (BMI) =16.5. (NA for Lebanon) 4. Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for = 3 months before screening. The following must be available in each subject’s source documentation: • A biopsy report to confirm the histological diagnosis. • A report documenting disease duration based upon prior colonoscopy. NOTE: If this documentation is not available at the time of screening, a colonoscopy with biopsy to confirm the diagnosis is required during the screening period. 5. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy (if preferred), including biopsy sample collection, during screening after all other inclusion criteria have been met. 6. Subjects must have moderate to severe active UC, defined as a total Mayo score of = 6, including a centrally read endoscopic subscore = 2, rectal bleeding subscore =1, and stool frequency subscore = 1 at baseline (Visit 2). 7. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis). 8. Subjects must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as mesalamine (5-ASA), glucocorticoids, immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]), or anti-TNF (refer to Appendix 4 for guidance). 9. Subjects receiving any treatment(s) for UC described in Section 5.2.1 of the protocol are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time. 10. Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use appropriate contraception for the duration of the study.
Exclusion criteria
Exclusion criteria: 1. Subjects with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn’s disease. 2. Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed.) 3. Subjects with past medical history or presence of toxic megacolon. 4. Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period. 5. Subjects at risk for colorectal cancer must have a colonoscopy (Eaden and Mayberry 2002) performed during the screening period with results available within 10 days before the baseline visit (Visit 2), unless the subject has had a surveillance colonoscopy performed within 1 year prior to screening, and any adenomatous polyps found at that examination have been excised. Colonoscopy report and pathology report (if biopsies are obtained) from the colonoscopy performed during screening or in the prior year confirming no evidence of dysplasia and colon cancer must be available in the source documents. Subjects at risk for colorectal cancer include, but are not limited to: • Subjects with extensive colitis for =8 years or disease limited to left side of colon (ie, distal to splenic flexure) for =10 years before screening, regardless of age. • Subjects =50 years of age at the time of signing of the informed consent form. 6. Subjects have had prior treatment with SHP647 (formerly PF-00547659). 7. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients. 8. Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2). 9. Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2). 10. Subjects have received any nonbiologic treatment with immunomodulatory properties (other than their current background UC treatment) within 30 days before baseline (Visit 2). 11. Subjects have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule). 12. Subjects have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening endoscopic procedure. 13. Subjects have received leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or plasma exchange within 30 days before baseline (Visit 2). 14. Subjects have participated in other investigational studies within either 30 days or 5 half-lives of investigational product used in the study (whichever is longer) before baseline (Visit 2). 15. Subjects have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2). 16. Subjects with active enteric infections (positive stool culture and sensitivity), Clostridium difficile infection or pseudomembranous colitis [subjects with C. difficile infection at screening may be allowed re-test after treatment], evidence of active cytomegalovirus infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmosis or parasitic infections
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Remission is defined as a composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy as follows: • stool frequency subscore of 0 or 1 with at least a 1-point change from baseline AND • rectal bleeding subscore of 0 AND • endoscopic subscore of 0 or 1 (modified, excludes friability).;Timepoints: Week 12;Measure: Remission at week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Endoscopic remission, as defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability);Timepoints: Week 12;Measure: Endoscopic remission at week 12;Name: Clinical remission, as defined by stool frequency subscore of 0 or 1 with at least a 1-point change from baseline in stool frequency subscore, and rectal bleeding subscore of 0;Timepoints: Week 12;Measure: Clinical remission at week 12 ;Name: Clinical response based on composite score. It is defined as a decrease from baseline in the composite score of patient-reported symptoms using daily e-diary and centrally read endoscopy of at least 2 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding =1 point or a subscore for rectal bleeding =1.;Timepoints: Week 12;Measure: Clinical response at week 12;Name: Mucosal healing based on endoscopic and histological assessment. it s defined by centrally read endoscopic subscore 0 or 1 (modified, excludes friability) and centrally read Geboes score of =2.;Timepoints: Week 12;Measure: Mucosal Healing at week 12;Name: Remission, defined as a total Mayo score =2 with no individual subscore (stool frequency, rectal bleeding, endoscopy [modified, excludes friability], and physician’s global assessment) exceeding 1;Timepoints: Week 12;Measure: Remission at week 12;Name: Clinical response based on total Mayo score. Clinical response (Mayo) is defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding =1 point or a subscore for rectal bleeding =1.;Timepoints: Week 12;Measure: Clinical response based on Mayo score at week 12 ;Name: Partial Mayo score =2 with no individual subscore >1. The partial Mayo score does not include the endoscopy subscore.;Timepoints: Weeks 4, 8 and 12;Measure: Partial Mayo score at weeks 4, 8 and 12;Name: Clinical remission as defined by stool frequency subscore of 0 or 1 with at least a 1-poi | — |
Countries
Argentina, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Colombia, Democratic People Republic of Korea, Estonia, France, Greece, Hungary, Ireland, Japan, Lebanon, Mexico, Portugal, Slovakia, Spain, Switzerland, Ukraine, United States of America
Contacts
Public ContactAziz Zoghbi
CRO
Outcome results
None listed