Celgene UC

Principal Investigator: John  Valentine
Keywords: Ulcerative Colitis , Apremilast Department: Gastroenterology
IRB Number: 00078910 Co Investigator:  
Specialty: Gastroenterology
Sub Specialties: Inflammatory Bowel Disease/Crohn's/Ulcerative Colitis
Recruitment Status: Recruiting

Contact Information

Heather Munk
heather.munk@hsc.utah.edu
801-587-9092

Brief Summary

Objectives
Primary Objective
To evaluate the clinical efficacy of apremilast (30 mg twice daily [BID] and 40 mg BID),
compared with placebo, in subjects with active UC.
Secondary Objectives
  • To evaluate the safety and tolerability of apremilast (30 mg BID and 40 mg BID), compared with placebo, in subjects with active UC
  • To evaluate the long-term safety in subjects with active UC, receiving apremilast (30 mg BID or 40 mg BID)
 
Exploratory Objectives
  • To evaluate the onset of clinical effect of apremilast (30 mg BID and 40 mg BID), compared with placebo, in subjects with active UC
  • To evaluate the benefit of apremilast (30 mg BID and 40 mg BID) on health-related quality of life (HRQoL) outcome measures, compared with placebo, in subjects with active UC
  • To evaluate UC-related health outcomes (such as hospitalizations and surgeries) in subjects with active UC treated with apremilast (30 mg BID and 40 mg BID)
  • To evaluate the durability of response in subjects with active UC, receiving apremilast (30 mg BID or 40 mg BID)
 
Pharmacokinetic (PK) Objectives, Pharmacodynamic (PD) Objectives, and Pharmacogenetic
(PG) Objective
  • To characterize the PK of apremilast (30 mg BID and 40 mg BID) in subjects with active UC
  • To explore the relationship between apremilast exposure and the efficacy of apremilast (30 mg BID and 40 mg BID) in subjects with active UC
  • To evaluate the change in biomarkers such as high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (FCP) in response to apremilast (30 mg BID and 40 mg BID) compared with placebo in subjects with active UC
  • To explore the PD effects of apremilast (30 mg BID and 40 mg BID) such as inflammatory cell infiltration, tissue destruction and gene expression in colonic mucosal biopsies from subjects with active UC
  • To explore the association of the PD parameters with the efficacy of apremilast (30 mg BID and 40 mg BID) in subjects with active UC
  • To explore the association of PG markers with the efficacy of apremilast (30 mg BID and 40 mg BID) in subjects with active UC

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Male or female aged 18 and over at the time of signing the informed consent.
  2. Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
  3. Must be able to adhere to the study visit schedule and other protocol requirements.
  4. Diagnosis of UC with duration of at least 3 months prior to the Screening Visit.
  5. TMS ≥ 6 to ≤ 11 (range: 0-12) prior to randomization in the study.
  6. Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.
  7. Subjects are required to have a colonoscopy if not performed within 12 months of the Screening Visit.
  8. Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5- aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).
  9. Subjects receiving oral corticosteroids may continue their use during the study, provided that the dose (prednisone ≤ 20 mg/day or equivalent, budesonide ≤ 9 mg/day) has been stable for 3 weeks prior to the Screening Visit. If oral corticosteroids were recently discontinued, discontinuation must have been completed at least 3 weeks prior to the Screening Visit. Corticosteroid doses should remain stable until the subject is eligible to start corticosteroids tapering, beginning at the Week 12 Visit.
  10. Oral aminosalicylates are permitted during the study, provided that treatment started at least 6 weeks prior to screening with a stable dose of at least 14 days prior to the Screening Visit. The dose of oral aminosalicylates must remain stable through Week 52 or until Week 104 for subjects who participate in the Extension Phase.
  11. Must meet the following laboratory criteria:
  12. White blood cell count ≥ 3000/mm3 (≥ 3.0 X 109/L) and < 14,000/mm3 (< 14 X 109/L)
  13. Platelet count ≥ 100,000/mm3 (≥ 100 X 109/L)
  14. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
  15. AST (SGOT) and ALT (SGPT) £ 2 X upper limit of normal (ULN). If initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the screening period
  16. Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) or albumin > lower limit of normal (LLN).  If initial test result is > 2 g/dL, one repeat test is allowed during the screening period
  17. Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
  18. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and the Baseline Visit. While on IP and for at least 28 days after taking the last dose of IP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options2 described below:

 

Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy

OR

 

Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide

  1.  Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on investigational product and for at least 28 days after the last dose of investigational product.

Exclusion Criteria

The presence of any of the following will exclude a subject from enrollment:

  1. Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
  2. Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).
  3. Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
  4. Clinical signs suggestive of fulminant colitis or toxic megacolon.
  5. Evidence of pathogenic enteric infection.
  6. History of colorectal cancer or colorectal dysplasia (with the exception of adenomatous colonic polyps that have been completely resected).
  7. Prior use of any TNF inhibitor (or any biologic agent).
  8. Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.
  9. Use of IV corticosteroids within 2 weeks of the Screening Visit.
  10. Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks the Screening Visit.
  11. Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
  12. History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.
  13. Prior history of suicide attempt at any time in the subject’s lifetime prior to randomization in the study or major psychiatric illness requiring hospitalization within 3 years of study randomization.
  14. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study.
  15. Pregnant or breast feeding.
  16. History of any of the following cardiac conditions within 6 months of screening: myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery, interventional cardiac catheterization (with or without a stent placement), interventional electrophysiology procedure, or presence of implanted defibrillator.
  1. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease and herpes zoster), human immunodeficiency virus (HIV), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) or oral antibiotics within 4 weeks of screening.
  2. Subjects with active hepatitis B infection, as described in Appendix E, are ineligible for the study. Subjects without current hepatitis B infection, as described in Appendix F, may participate in the study.
  3. Subjects who are confirmed positive for hepatitis C are not eligible for the study.
  4. History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
  5. History of malignancy, except for:
    1. Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas
    2. Treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years
  6. Any condition that could affect oral drug absorption, including gastric resections, gastroparesis or bariatric surgery, such as gastric bypass.
  7. Subject has received any investigational drug or device within 1 month or 5 elimination half-lives, whichever is longer, prior to the Screening Visit.
  8. History of alcohol, drug, or chemical abuse within the 6 months prior to screening.
  9. Known hypersensitivity to apremilast or any excipients in the formulation.