A Phase 1b Study to Assess the Safety and Anti-inflammatory Effects of Two Different Doses of SRT2104 in Patients With Ulcerative Colitis

This is an interventional treatment trial for Colitis, Ulcerative Read More

Inclusion Criteria:

• Mild to moderately active ulcerative colitis as evidenced by Mayo score 6-10 (inclusive) with rectal bleeding score ≥1, endoscopy score between 2-3 (inclusive), and physician's rating of disease activity <3 at Day -5
• Colonic inflammation extending proximal to the rectum (i.e., greater than 15 cm in extent) on baseline sigmoidoscopy at Day -5
• Confirmed diagnosis of ulcerative colitis for at least 3 months prior to the Screening Visit (Visit 1)
• Male or female between 18 and 75 years, inclusive
• Body weight >50 kg and BMI ≥18 kg/m^2 at Screening (Visit 1)
• Capable of giving written informed consent, and willing and able to comply with the requirements of the protocol
• Female subjects of child-bearing potential must be willing to use reliable contraception from Visit 1 through the follow-up visit (Day 70)

Exclusion Criteria:

• Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, segmental colitis associated with diverticulosis, ischemic colitis, or radiation-induced colitis based on medical history, endoscopy, and/or histological findings
• Presence of infectious colitis as evidenced by positive stool culture for enteric pathogens or positive stool Clostridium difficile cytotoxin assay at Visit 1
• Presence of chronic liver disease, with the exception of known Gilbert's syndrome
• A positive pre-study Hepatitis B surface antigen, Hepatitis C antibody or HIV at Visit 1
• Past or present disease that is judged by the investigator to have the potential to interfere with the study procedures or compromise the subject's safety
• History of malignant neoplasm within the past 5 years, other than localized basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ that has been resected or definitively treated with standard approaches
• Prior diagnosis of flat colonic dysplasia or unresected raised colonic dysplasia (adenoma-like lesion or mass)
• History of regular alcohol consumption within 6 months of the Screening (Visit 1) defined as an average weekly intake of >14 drinks (one drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits) or presence of recreational drug abuse or dependence
• Known bleeding disorders
• Bowel surgery within 12 months prior to Visit 1
• History of colectomy or partial colectomy
• Treatment with oral aminosalicylates at doses >4.8 g per day or aminosalicylate dose modification (except transient shift lasting up to 3 days) within 4 weeks prior to study Day -5 (Note: if on this type of treatment, the dose must remain constant throughout the study treatment period)
• Treatment with rectal aminosalicylates at any dose within 2 weeks of study Day -5
• Treatment with systemic or rectal corticosteroids within 4 weeks of study Day -5
• Treatment with TNFα inhibitors or other biologics within 2 months prior to study Day -5
• Treatment with other immunosuppressants (azathioprine or 6-mercaptopurine), if initiated within 3 months prior to study Day -5, or if changed in terms of dose within 3 months prior to study Day -5 (Note: if on this type of treatment, the dose must remain constant throughout the study treatment period)
• Regular use of pro-biotic or prebiotic preparations within 4 weeks of study Day -5 visit
• Regular use of non-steroidal anti-inflammatories (NSAIDS) or aspirin, except low dose (cardioprotective ≤325 mg/day) aspirin, within 7 days prior to study Day -5
• Participation in a clinical trial and treatment with an study drug within 3 months prior to Visit 1
• Have a clinically significant finding on a chest X-ray performed at Visit 1 or within 3 months of Visit 1
• Have an abnormal 12-lead electrocardiogram (ECG) with one or more changes considered to be clinically significant on medical review

• Renal or liver impairment based on laboratory values obtained at Visit 1 and defined as:

  • serum creatinine level of ≥1.4 mg/dL for females and ≥1.5 mg/dL for males, or
  • AST and/or ALT ≥2x upper limit of normal (ULN), or
  • bilirubin > 1.5xULN (an isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)
  • Hemoglobin less than 8.5 g/dL at Visit 1
  • Have any other reason which, in the opinion of the investigator, would confound the conduct or interpretation of the study