Crohn Disease CD
Conditions
Interventions
The study consists of a screening period up to 6 weeks and a 16-week treatment period. After the screening period, eligible subjects will be randomized to receive 1 of 3 treatments (25 mg SHP647, 75
for subjects who fulfill the entry criteria) or a long-term safety extension (LTS) study (SHP647-304
for subjects who do not
fulfill the entry criteria for Study SHP647-307) as shown in Figure 1. Subjects who withdraw early from the 16-week treatment period or who do not wish to enter the maintenanc
randomization ratio of 3:3:2 to receive SC injections of 25 mg SHP647, 75 mg SHP647, or placebo
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 assent as applicable to participate in the study. 3. Subjects must be between =18 and =80 years of age at the time of the signing of the informed consent/assent form. 4. Subjects must have active moderate to severe ileal (terminal ileum), ileocolic, or colonic CD at baseline (Visit 2) as defined by: a. CDAI score between 220 and 450 (inclusive) AND b. Presence of ulcerations that are characteristic to CD, as determined by a colonoscopy performed during screening, and as defined by the SES-CD >6 (SES-CD =4 for isolated ileitis) AND c. Meeting the following subscores in the 2-item PRO: i. Abdominal pain subscore =5 (average worst daily pain on the 11-point NRS) AND abdominal pain subscore =2 (average daily pain on the 4-point abdominal pain variable of CDAI) over the 7 most recent days out of the 10 days before colonoscopy preparation (may or may not be contiguous) AND/OR ii. Average of the daily stool frequency subscore =4 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days out of the 10 days before colonoscopy preparation (may or may not be contiguous). 5. Subjects must have a documented diagnosis (endoscopic with histology) of CD for =3 months before screening. Documented diagnosis is defined as: • A biopsy report to confirm the histological diagnosis AND • A report documenting disease duration based upon prior colonoscopy. Note: If a biopsy report is not available in the source document at the time of screening, a biopsy must be performed during the screening colonoscopy and the histology report should be consistent with the CD diagnosis. If the histology diagnosis is not clear at this time point, the subject should not be randomized. 6. Subjects must be willing and able to undergo a colonoscopy during screening after all other inclusion criteria have been met. 7. Subjects must have had an inadequate response to, or lost response to, or had an intolerance to at least 1 conventional treatment such as sulfasalazine or mesalamine (5-ASA), glucocorticoids, immunosuppressants (AZA, 6-MP, or MTX), or anti-TNF (refer to Appendix 4 for guidance). Subjects who have had an inadequate response to sulfasalazine or mesalamine should have also failed at least 1 other conventional treatment such as glucocorticoids. 8. Subjects receiving any treatment(s) for CD 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. 9. 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 (as described in Section 4.4) 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 ulcerative colitis. 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 presence of enterovesical (ie, between the bowel and urinary bladder) or enterovaginal fistulae. 5. Subjects with current symptomatic diverticulitis or diverticulos is. 6. Subjects with obstructive 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 CD during the treatment period. 7. Subjects with past medical history of multiple small bowel resections resulting in clinically significant short bowel syndrome. 8. Subjects requiring total parenteral nutrition. 9. Subjects with past medical history of bowel surgery resulting in an existing or current stoma. Subjects who had a j-pouch are excluded as a j-pouch could result in a stoma. 10. Subjects have had prior treatment with SHP647 (formerly PF-00547659). 11. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients. 12. Subjects have received any nonbiologic treatment with immunomodulator y properties (other than AZA, 6-MP, or MTX) or continuous antibiotics (>2 weeks) for the treatment of CD within 30 days before baseline (Visit 2). 13. Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2). 14. Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2). 15. Subjects have ever received anti-integrin/adhesion molecule treatment (eg, natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhes ion molecule). 16. Subjects have received lymphocytes apheresis or selective monocyte granulocytes apheresis within 60 days before baseline (Visit 2). 17. Subjects have received enteral nutrition treatment within 30 days before baseline (Visit 2). 18. Subjects have received parenteral or rectal glucocorticoids or rectal 5-ASA within 14 days before screening colonoscopy. 19. Subjects have taken >20 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 14 days before baseline (Visit 2) or have taken =40 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 6 weeks before baseline (Visit 2). 20. 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 screening (Visit 1). 21. Subjects have received a live (attenuated) vaccine within 30 days before baseline (Visit 2). 22. 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 retest after treatment], evidence of active cytomegalovir us infection or Listeria monocytogenes, known active invasive fungal infections such as histoplasmos is or parasitic infections, clinically significan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Clinical remission based on 2-item patient-reported outcome (PRO) (abdominal pain severity and very soft stool/liquid stool frequency) ;Timepoints: week 16;Measure: Clinical remission at week 16;Name: Inducing endoscopic response based on centrally read colonoscopy.;Timepoints: Week 16;Measure: Endoscopic response at week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Clinical remission as measured by CDAI;Timepoints: week 16;Measure: Clinical remission at week 16;Name: Enhanced endoscopic response based on centrally read colonoscopy;Timepoints: Week 16;Measure: Enhanced endoscopic response at week 16;Name: Clinical remission based on abdominal pain severity and very soft stool/liquid stool frequency (alternate thresholds);Timepoints: Week 16;Measure: Clinical response at week 16;Name: Clinical response based on patient-reported clinical signs and symptoms (as measured by 2-item PRO);Timepoints: Week 16;Measure: Clinical response at week 16;Name: Clinical remission based on patient-reported clinical signs and symptoms (as measured by 2-item PRO) as well as inducing endoscopic response based on centrally read colonoscopy in the same subject;Timepoints: week 16;Measure: Clinical remission at week 16;Name: Endoscopic healing based on centrally read colonoscopy.;Timepoints: Week 16;Measure: Endoscopic healing at Week 16 | — |
Countries
Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Colombia, Democratic People Republic of Korea, Estonia, Hungary, Ireland, Japan, Lebanon, Mexico, Portugal, Slovakia, Spain, Ukraine, United States of America
Contacts
Public ContactAziz Zoghbi
CRO
Outcome results
None listed