Crohn's disease MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: SHP647
Product Code: SHP647
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ontamalimab
Current Sponsor c
Sponsors
Shire Human Genetic Therapies, Inc.
Eligibility
Sex/Gender
All
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. Note: Subjects 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 4point 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). AND c. 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) Note that the subject must be confirmed as meeting the CDAI score and PRO subscore requirements before a colonoscopy is done. 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 in which the description of the histological findings is consistent with the CD 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 description does not support the CD 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 (see to Appendix 4 of the protocol 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
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 diverticulosis. 6.Subjects with clinically significant obstructive colonic stricture, or who have a history of bowel surgery within 6 months before screening, or who are likely to require surgery for CD during the treatment period. Subjects who have undergone previous colonic resection or ileocolectomy more than 6 months before screening must have at least 25 cm of colon remaining. 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 ontamalimab (formerly PF00547659; SHP647). 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 immunomodulatory 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/adhesion 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, >9 mg/day of budesonide, 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 16; Main Objective: The coprimary objectives of this study are to evaluate the efficacy of ontamalimab in subjects with moderate to severe Crohn's Disease (CD) in: Inducing clinical remission based on 2-item patient-reported outcome (PRO) (abdominal pain severity and very soft stool/liquid stool frequency) Inducing endoscopic response based on centrally read colonoscopy. ; Secondary Objective: The key secondary objectives are as follows: To evaluate the efficacy of ontamalimab in inducing clinical remission as measured by Crohn's Disease Activity Index (CDAI) To evaluate the efficacy of ontamalimab in inducing enhanced endoscopic response based on centrally read colonoscopy To evaluate the efficacy of ontamalimab in inducing clinical remission based on abdominal pain severity and very soft stool/liquid stool frequency (alternate thresholds) To evaluate the efficacy of ontamalimab in inducing clinical response based on patient-reported clinical signs and symptoms (as measured by 2-item PRO) To evaluate the efficacy of ontamalimab in inducing 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 To evaluate the efficacy of ontamalimab in inducing endoscopic healing based on centrally read colonoscopy. ; Primary end point(s): The coprimary efficacy endpoints are: ? Clinical remission at the Week 16 visit as defined by the following: 2-item PRO subscores of average worst daily abdominal pain =3 (based on 11-point NRS) over the 7 most recent days and average daily stool frequency =2 of type 6/7 (very soft stools/liquid st | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoints are as follows: ? Clinical remission at the Week 16 visit as measured by a CDAI score of <150. ? Enhanced endoscopic response at Week 16 as measured by a decrease in SES-CD of at least 50% from baseline. ? Clinical remission at the Week 16 visit as defined by the following: 2-item PRO subscores of average worst daily abdominal pain =1 (based on the 4-point scale) over the 7 most recent days and average daily stool frequency =3 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days. The 7 most recent days may or may not be contiguous during the 10 days of data collection before colonoscopy preparation, depending on days to be excluded because of missing data. If fewer than 7 days are available, the endpoint will be calculated on all available most recent 6 or 5 days. If fewer than 5 days are available, the endpoint will be treated as missing. ? Clinical response at the Week 16 visit as measured by the 2-item PRO and defined as meeting at least 1 of the following 2 criteria: o A decrease of =30% and at least 2 points from baseline in the average daily worst abdominal pain over the 7 most recent days*, with the average daily stool frequency of type 6/7 (very soft stools/liquid stools) either: (a) Not worsening from baseline and/or (b) Meeting the criteria for clinical remission, ie, 2-item PRO subscore of average daily stool frequency =2 of type 6/7 (very soft stools/liquid stools) as shown in the BSFS over the 7 most recent days* o A decrease of =30% from baseline in the average daily s | — |
Countries
Australia, Austria, Brazil, Croatia, Czech Republic, Germany, Israel, Italy, Japan, Lithuania, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, South Africa, United Kingdom, United States
Contacts
Public ContactChantal L. Letourneau
Shire Human Genetic Therapies, Inc.
Outcome results
None listed