Research study to determine whether an investigational drug, SHP647, is safe and effective long term in the treatment of moderate to severe Ulcerative Colitis or Crohn's Disease (AIDA)

Phase 1

• Conditions: lcerative colitis or Crohn's Disease; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 10017947 - Gastrointestinal disorders; MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2017-000574-11-DE
• Lead Sponsor: Shire Human Genetic Therapies, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-25
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 2453

Inclusion Criteria

Subjects with UC Entering from an Induction or Maintenance Study:
1. Subjects must have been previously enrolled in study SHP647-301, SHP647 302, or SHP647-303, and reached 1 of the following clinical trial milestones:
- Completed the Week 12 visit in induction study SHP647-301 or SHP647 302, and did NOT achieve a clinical response. Clinical response is defined as: 1) 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, OR 2) a decrease from the induction study (SHP647-301 or SHP647-302) baseline total Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.
- Completed the Week 52 visit in maintenance study SHP647-303.
- Withdrew early from maintenance study SHP647-303 due to treatment failure, defined by an endoscopic subscore that has increased by at least 1 point over baseline in the maintenance study or a value =2 plus an increase in clinical subscore (stool frequency + rectal bleeding score) of
at least 2 points. Centrally read endoscopic subscores will be used to determine treatment failure.
2. Subjects receiving any treatment(s) for UC described in Section 5.2.1 are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.

Subjects with UC Entering Directly:
1. Subjects must be between =16 and =80 years of age at the time of the signing of the informed consent/assent form. Note: Subjects <18 years of age must weigh =40 kg and must have body
mass index =16.5 kg/m2.
2. Subjects must meet at least 1 of the 3 criteria below:
-Have previously received ontamalimab (SHP647) in a Shire or Pfizersponsored Phase 1 or Phase 2
clinical trial
-Have previously received vedolizumab
-Live in a country that has reached its enrollment cap for induction studies (SHP647-301 and/or
SHP647-302).
3. 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.
4. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy (if preferred or required per exclusion criterion #5), during screening after all other inclusion criteria have been met.
5. 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 1).
6. Subjects must have evidence of UC extending proximal to the rectum (ie, not limited to proctitis).
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 mesalamine (5-aminosalicylic acid
[5ASA]), glucocorticoids, immunosuppressants (azathioprine, 6-mercaptopurine [6-MP], or methotrexate), or anti-tumor necrosis factor (TNF).
8. Subjects receiving any treatment(s) for UC described in Section 5.2.2.1 of the protocol are eligible provided they have been, and are anticipated to be, on a stable dose for the designat

Exclusion Criteria

Subjects with UC Entering from an Induction or Maintenance
Study/Subjects with CD
1. Subjects who had major protocol deviation(s) (as determined by the sponsor) in previous studies.
2. Subjects who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in previous studies.
3. Subjects who are likely to require major surgery for UC/CD.
4. Subjects are females who became pregnant during the previous UC/CD studies, females who are lactating, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue using appropriate contraception methods (ie, highly effective methods for female and medically appropriate methods for male study subjects) through the
conclusion of study participation.
5. Subjects who do not agree to postpone donation of any organ or tissue, including male subjects who are planning to bank or donate sperm and female subjects who are planning
to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of
investigational product.
6. Subjects who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures.
7. Subjects who have a newly-diagnosed malignancy or recurrence of malignancy
8. Subjects who have developed any major illness/condition or evidence of an unstable clinical condition (except disease under study) or local active infection/infectious illness) that, in the investigator's judgment, will substantially increase the risk to the subject if he or she participates in the study.
9. Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study
results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
10. Subjects with known exposure to ?.tuberculosis (TB) since testing at screening in previous UC/CD studies and who have been advised to require treatment for latent or active disease, but who are without agenerally accepted course of treatment.

Subjects with UC Entering directly
1. Subjects with indeterminate colitis, microscopic colitis, nonsteroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of CD.
2. Subjects with colonic dysplasia or neoplasia.
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 1), 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. 6. Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
7. Subjects have received anti-TNF treatment within 60 day

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified