A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 302)
a study on Inflammatory Bowel Disease
The purpose of this study is to evaluate the efficacy of SHP647 in inducing remission, based on composite score of patient-reported symptoms and centrally read endoscopy, in subjects with moderate to severe ulcerative colitis (UC).
A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel Group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis (FIGARO UC 302)
Ulcerative Colitis Colitis Ulcer Colitis, Ulcerative SHP647 SHP647 25 mg SHP647 75 mg
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Open to people ages 16-80
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study.
- Subjects and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
- 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.
- Subjects must be between 16 and 80 years of age at the time of the signing of the informed consent/assent form.
NOTE: Subjects less than (<) 18 years of age must weigh greater than or equal to (>=)40 kg and must have body mass index (BMI) >=16.5.
- 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.
- 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.
- 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).
- Subjects must have evidence of UC extending proximal to the rectum ( that is [ie,]not limited to proctitis).
- Subjects must have had an inadequate response to, or lost response to, at least 1 conventional treatment such as mesalamine (5-aminosalicylate [ASA]), glucocorticoids,immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate[MTX]), or anti-tumor necrosis factor (TNF).
- Subjects receiving any treatment(s) for UC are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
- . 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 acceptable contraception for the duration of the study.
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Subjects are excluded from the study if any of the following exclusion criteria are met.
- Subjects with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease.
- Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed.)
- Subjects with past medical history or presence of toxic megacolon.
- 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.
- Subjects at risk for colorectal cancer must have a colonoscopy performed during the screening period with results available within 10 days before the baseline visit(Visit 2), unless the subject has had a colonoscopy 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 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.
- Subjects have had prior treatment with SHP647 (formerly PF-00547659).
- Subjects with known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients.
- Subjects have received anti-TNF treatment within 60 days before baseline (Visit 2).
- Subjects have received any biologic with immunomodulatory properties (other than anti-TNFs) within 90 days before baseline (Visit 2).
- . Subjects have ever received anti-integrin/adhesion molecule treatment (example:natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational anti-integrin/adhesion molecule).
- . Subjects have received parenteral or rectal glucocorticoids, or rectal 5-ASA, within 14 days before screening endoscopic procedure.
- . 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).
- . Subjects have received a live (attenuated) vaccine within 30 days before the baseline visit (Visit 2).
- . 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, clinically significant underlying disease that could predispose the subjects to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization)within 4 weeks before the baseline visit (Visit 2).
- . Subjects with abnormal chest x-ray findings at screening (Visit 1), such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy. (A chest x-ray performed up to 12 weeks before study entry [screening, Visit 1] may be used if available; documentation of the official reading must be located and available in the source documentation.)
- . Subjects with evidence of active or latent infection with Mycobacterium tuberculosis(TB) who have not completed a generally accepted full course of treatment before randomization are excluded. All other subjects must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon gamma release assay(IGRA) performed.
Subjects who have no history of previously diagnosed active or latent tuberculosis are excluded if they have a positive Mantoux (PPD) tuberculin skin test (ie >=5 millimeter[mm] induration) or a positive IGRA (the latter to be tested at the site's local laboratory) during screening or within 12 weeks before randomization. If IGRA test cannot be performed locally, a central laboratory may be used, with prior agreement from the sponsor.
- An IGRA is strongly recommended for subjects with a prior Bacillus Calmette-Guerin (BCG) vaccination, 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 performed locally. Acceptable IGRA products include Quantiferon TB Gold In-Tube Test.
- If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. In subjects with no history of treated active or latent tuberculosis, a positive test on repeat will exclude the subject. Subjects with a history of active or latent tuberculosis infection must follow instructions for "Subjects with a prior diagnosis of active or latent tuberculosis are excluded unless both of the following criteria are met" in this criterion.
- Subjects with repeat indeterminate IGRA results, with no prior TB history, may be enrolled after consultation with a pulmonary or infectious disease specialist who determines low risk of infection (ie, subject would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action). This consultation must be included in source documentation.
Results from a chest x-ray, taken within the 3 months before or during screening(Visit 1) must show no abnormalities suggestive of active TB infection as determined by a qualified medical specialist.
Subjects with a prior diagnosis of active or latent tuberculosis are excluded unless both of the following criteria are met:
- The subject has previously received an adequate course of treatment for either latent (eg, 9 months of isoniazid or an acceptable alternative regimen, in a locale where rates of primary multidrug TB resistance are less than (<) 5%.Subjects from regions with higher rates of primary multidrug TB resistance are excluded) or active (acceptable multidrug regimen) TB infection. Evidence of diagnosis and treatment must be included in source documentation. Consultation with a pulmonary or infectious disease specialist to confirm adequate treatment(ie, subject would be acceptable for immunosuppressant [eg, anti-TNF] treatment without additional action) must be performed during the screening period. The consultation report must be included in source documentation prior to enrollment.
- A chest x-ray performed within 3 months prior to screening (Visit 1) or during screening (Visit 1) indicates no evidence of active or recurrent disease, and documentation of interpretation by a qualified medical specialist must be included in source documentation.
- . Subjects with a pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening.
- . Subjects with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
- . Subjects with a transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed.
- . Subjects with a significant concurrent medical condition at the time of screening(Visit 1) or baseline (Visit 2), including, but not limited to, the following:
- Any major illness/condition or evidence of an unstable clinical condition (eg,renal, hepatic, hematologic, gastrointestinal (except disease under study),endocrine, cardiovascular, pulmonary, immunologic [eg, Felty's syndrome], 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.
- Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
- Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening (Visit 1).
- History of significant cerebrovascular disease within 24 weeks before screening(Visit 1).
- . Subjects who have had significant trauma or major surgery within 4 weeks before the screening visit (Visit 1), or with any major elective surgery scheduled to occur during the study.
- . Subjects with evidence of or suspected liver disease, liver injury due to methotrexate or primary sclerosing cholangitis.
- . Subjects with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). NOTE: if a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if the subject tests positive for antibody to Hepatitis B surface antigen (HBsAb also referred as anti-HBsAg) reflex testing.
- . Subjects with positive hepatitis C antibody (HCVAb) with confirmation by HCV-ribonucleic acid (RNA) polymerase chain reaction (PCR) reflex testing.
- . Subjects with any of the following abnormalities in hematology and/or serum chemistry profiles during screening. NOTE: Screening laboratory tests, if the results are considered by the investigator to be transient and inconsistent with the subject's clinical condition, may be repeated once during the screening period for confirmation.Results must be reviewed for eligibility prior to the screening endoscopy procedure.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >=2.0 times the upper limit of normal (ULN).
- Total bilirubin level >=1.5 times the ULN (except in subjects with documented diagnosis of Gilbert's syndrome).
- Hemoglobin level less than or equal to (<=) 80 gram per liter (g/L) (8.0 gram per deciliter [g/dL]).
Platelet count <=100 × 109 per liter (/L) (100,000 cells per cubicmillimeter[/mm3]) or >=1000 × 109/L (1,000,000 cells/mm3).
White blood cell count <=3.5 × 109/L (3500 cells/mm3).
Absolute neutrophil count (ANC) <2000 cells/mm3.
Serum creatinine level >=177 micromoles per liter [mcmol/L] (2 mg/dL) or estimated glomerular filtration rate (GFR) <40 ml/min/1.73m2 based on the abbreviated MDRD.
- . Subjects with known infection with human immunodeficiency virus (HIV).
- . Subjects who have, or who have a history of (within 2 years before screening [Visit 1]), serious psychiatric disease, alcohol dependency, or substance/drug abuse.
- . Subjects using medicinal marijuana (cannabis) or related products for recreational purposes, who have a known dependency per the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (including urine drug screen and medical history). Exceptions are those subjects who are prescribed marijuana (by a physician) for medicinal use and where the product is sourced from a licensed pharmacy/provider. Such subjects must be using the product, in a stable regimen, for at least 3 months before screening.
- . Subjects with any other severe acute or chronic medical or psychiatric condition or laboratory or 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.
- . Female subjects who are planning to become pregnant during the study period.
- . Male subjects who are planning to donate sperm must agree not to do so for the duration of the study and through 16 weeks after last dose of investigational product.
- . Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Shire employees directly involved in the conduct of the study.
- University of California San Diego not yet accepting patients
La Jolla California 92093 United States
- Gastro Health Center accepting new patients
Encinitas California 92024 United States