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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01453491
• Date of registration: 13/10/2011
• Prospective Registration: Yes
• Primary sponsor: Sirtris, a GSK Company
• Public title: A Phase 1b Study to Assess the Safety and Anti-inflammatory Effects of Two Different Doses of SRT2104 in Patients With Ulcerative Colitis
• Scientific title: A Phase 1b, Exploratory Study to Assess the Safety, Tolerability, Colonic Tissue Exposure, and Anti-Inflammatory Effects of Two Different Doses of SRT2104 in Subjects With Mild to Moderate Ulcerative Colitis
• Date of first enrolment: February 13, 2012
• Target sample size: 17
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01453491
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

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 TNFa 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: SRT2104

Primary Outcome(s)

Number of participants with adverse events and incidence of adverse events will be used as a measure of safety and tolerability of 50 mg and 500 mg of SRT2104 after repeat dosing for up to eight weeks in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

SRT2104 concentration in colonic tissue will be measured via endoscopic biopsy after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis [Time Frame: 56 days]

Secondary Outcome(s)

Simple Clinical Colitis Activity Index (SCCAI) will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

SRT2104 concentration in plasma will be measured after repeat dosing for up to 8 weeks in subjects with mild to moderate ulcerative colitis [Time Frame: 56 days]

Endoscopic scoring of colonic lesions assessed during flexible sigmoidoscopy will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

Histopathologic scoring of colonic tissue biopsies obtained via flexible sigmoidoscopy will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

Fecal calprotectin will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

Mayo score and Partial Mayo score will be used as a measure of the anti-inflammatory effect of SRT2104 after 8 weeks of treatment in subjects with mild to moderate ulcerative colitis [Time Frame: 75 days]

Secondary ID(s)

115951

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline