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 Crohn's Disease (CARMEN CD 305)
The purpose of this study is to evaluate the efficacy and safety of SHP647 in inducing clinical remission and endoscopic response in participants with moderate to severe Crohn's Disease.
16 Years to 80 Years
Accepting Healthy Volunteers?
- Participants must be between greater than or equal to (>=) 16 and less than or equal to (<=) 80 years of age; participants less than (<) 18 years of age must weigh >=40 kg and must have body mass index >=16.5 kg/m^2.
- Participants must have active moderate to severe ileal, ileocolic, or colonic CD at baseline as defined by CDAI, presence of ulcerations that are characteristic to CD as determined by a colonoscopy and as defined by the SES-CD score and assessed by the average worst daily abdominal pain and/or average daily stool frequency.
- Participants must have a documented diagnosis (endoscopic with histology) of CD for >=3 months before screening.
- Participants must be willing and able to undergo a colonoscopy during screening after all other inclusion criteria have been met.
- Participants 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-aminosalicylic acid [5-ASA]), glucocorticoids, or immunosuppressants (azathioprine [AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) or anti-tumor necrosis factor (anti-TNF). Participants who have had an inadequate response to sulfasalazine or mesalamine should have also failed at least 1 other conventional treatment such as glucocorticoids.
- Participants receiving treatment(s) for CD are eligible provided they have been, and are anticipated to be, on a stable dose for the designated period of time.
- Participants 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.
Key Exclusion Criteria:
- Participants with indeterminate colitis, microscopic colitis, non-steroidal anti-inflammatory drug-induced colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of ulcerative colitis.
- Participants with colonic dysplasia or neoplasia.
- Participants with past medical history or presence of toxic megacolon.
- Participants with presence of enterovesical or enterovaginal fistulae.
- Participants with current symptomatic diverticulitis or diverticulosis.
- Participants 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.
- Participants with past medical history of multiple small bowel resections resulting in clinically significant short bowel syndrome.
- Participants requiring total parenteral nutrition.
- Participants with past medical history of bowel surgery resulting in an existing or current stoma.
- Participants have had prior treatment with SHP647 (formerly PF-00547659).
- Participants with active enteric infections, Clostridium difficile infection or pseudomembranous colitis, 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 participants to infections, or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before baseline.
- Participants with abnormal chest x-ray or other imaging findings at screening, such as presence of active tuberculosis (TB), general infections, heart failure, or malignancy.
- Participants with evidence of active or latent infection with Mycobacterium tuberculosis (TB) or participants with this history who have not completed a generally accepted full course of treatment before baseline are excluded. All other participants must have either the Mantoux (purified protein derivative [PPD]) tuberculin skin test or interferon-gamma release assay (IGRA) performed.
- Participants 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.
- Participants with any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
- Participants with a significant concurrent medical condition at the time of screening or baseline, including, but not limited to, the following:
1. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, GI [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 participant if he or she participates in the study.
2. 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).
3. Presence of acute coronary syndrome (eg, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.
4. History of significant cerebrovascular disease within 24 weeks before screening.
- Participants who have had significant trauma or major surgery within 4 weeks before screening, or with any major elective surgery scheduled to occur during the study.
- Participants with evidence of cirrhosis with or without decompensation (ie, esophageal varices, hepatic encephalopathy, portal hypertension, ascites).
- Participants with primary sclerosing cholangitis.
- Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb).
- Participants with chronic hepatitis C (HCV) (positive HCVAb and hepatitis C ribonucleic acid [HCVRNA]).
Note: Participants who are HCVAb positive without evidence of HCVRNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCVRNA at least 12 weeks prior to baseline]).
- Participants with any of the following abnormalities in hematology and/or serum chemistry profiles during screening.
1. Alanine aminotransferase and aspartate aminotransferase levels >=3 x the upper limit of normal (ULN)
2. Total bilirubin level >=1.5 × ULN or >2.0 × ULN if the participant has a known documented history of Gilbert's syndrome
3. Hemoglobin level <=80 grams per liter (g/L) (8.0 gram per deciliter [g/dL])
4. Platelet count <=100 × 10^9 per liter (/L) (100,000 cells per cubic millimeter [cells/mm^3]) or >=1000 × 10^9/L (1,000,000 cells/mm^3)
5. White blood cell count <=3.5 × 10^9/L (3500 cells/mm^3)
6. Absolute neutrophil count <2 × 10^9/L (2000 cells/mm3)
7. Serum creatinine level >1.5 x the ULN or estimated glomerular filtration rate <30 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) based on the abbreviated Modification of Diet in Renal Disease Study Equation.
Note: if platelet count is <150,000 cells/mm^3, a further evaluation should be performed to rule out cirrhosis, unless another etiology has already been identified.
- Participants with known human immunodeficiency virus (HIV) infection based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site's local laboratory in accordance with country requirements, or tested at the central laboratory.
Note: A documented negative HIV test within 6 months of screening is acceptable and does not need to be repeated.
- Participants who have, or who have a history of (within 2 years before screening), serious psychiatric disease, alcohol dependency, or substance/drug abuse of any kind including abuse of medicinal marijuana (cannabis).
- Participants 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 participant inappropriate for entry into this study.
- Female participants who are planning to become pregnant during the study period.
- Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm, or female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.
NOTE: The above Inclusion/Exclusion criteria are NOT exhaustive and other Inclusion/ Exclusion criteria as defined in the protocol may apply.