Study of the Safety and Efficacy of Zoenasa® Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis

• Change in modified UCDAI at 3 weeks [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  Change from baseline in the modified Ulcerative Colitis Disease Activity Index (modified UCDAI) score at the end of the 3 week treatment period of Zoenasa™ Rectal Gel compared with mesalamine
• Clinical and endoscopic remission rates at 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline
• Clinical and endoscopic remission rates at 3 weeks [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline
• Clinical improvement rate after 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Clinical improvement rate after 3 weeks [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
• Endoscopic improvement rate at 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Endoscopic improvement rate at 3 weeks [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
• Change from baseline in endoscopic appearance after 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Change from baseline in endoscopic appearance after 3 weeks [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
• Time to resolution of rectal bleeding [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]
• Relapse rates at 6 weeks [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]

This double-blind, randomized, comparator-controlled Phase II study is designed to establish the safety and efficacy of Zoenasa Rectal Gel compared to mesalamine enema in subjects with left-sided ulcerative colitis, as measured by the modified ulcerative colitis disease activity index (UCDAI), over 6 weeks of treatment. In this study, two cohorts of subjects will receive either Zoenasa-1:4 (1.0g NAC; 4.0g 5-ASA) investigational drug enema therapy or comparator mesalamine enema (4.0g 5-ASA). The study will enroll subjects randomized equally into the 2 cohorts. Each cohort will enroll approximately 60 subjects. The two arms of the trial will be enrolled concurrently in a randomized fashion.

• Ulcerative Colitis
• Left-sided Ulcerative Colitis
• Distal Ulcerative Colitis

• Drug: Zoenasa-1:4
  Zoenasa Rectal Gel (4.0g mesalamine [5-ASA], 1.0g N-acetylcysteine [NAC]; 60ml)
• Drug: Mesalamine Enema
  Mesalamine Rectal Suspension Enema (4.0g mesalamine [5-ASA], 60ml)

• Experimental: Zoenasa-1:4
  Intervention: Drug: Zoenasa-1:4
• Active Comparator: Mesalamine Enema
  Intervention: Drug: Mesalamine Enema

Inclusion Criteria:

• Male and female subjects are eligible if they are ≥ 18 years of age and ≤ 64 years.
• They have a documented history of idiopathic ulcerative colitis based on endoscopic and/or histologic findings involving the left side of the colon, with mild to moderate active disease.
• Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI score of 4-10, inclusive, with a Physician's rating of disease score of 2 points or less (mild or moderate active ulcerative colitis), rectal bleeding score of 1 or more (based on subject diary), and mucosal appearance score (based on endoscopy) of 1 point or more at baseline.

• Laboratory data:

  • White blood cell count between 4.0 - 12.0 K/mm3
  • Platelet count: 150 - 500 K/mm3
  • Hemoglobin > 10.0 g/dL
  • Total bilirubin < 1.5 mg/dL
  • Aspartate aminotransferase < 100 u/dL
  • Alanine aminotransferase < 100 u/dL
  • Alkaline phosphatase < 250 u/dL
  • Blood urine nitrogen < 40 mg/dL
  • Creatinine < 1.5 mg/dL
• Satisfies one of the following:
• Female subjects of childbearing potential must have a negative urine pregnancy test at screening; surgically sterile, post-menopausal, abstinent, or patient or partner agree to use a medically appropriate form of birth control from screening to until 1 month after the last dose of study medication.
• Male subjects must be surgically sterile, abstinent, or patient or partner compliant with a contraceptive regimen from screening to until 1 month after the last dose of study medication.
• They are able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.

Exclusion Criteria:

• They have documented history of proximal or universal ulcerative colitis, proctitis or active proctitis confined to 15cm or less from the anal verge.
• They demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis.
• They receive a Physician's rating of disease severity as part of the modified UCDAI of 3 (severe disease) or an aggregate score of 11 or greater.
• They have shown prior documented history of evidence of high grade dysplasia on biopsy from endoscopic examinations.
• Their stool contains enteric pathogens or Clostridium difficile toxins.
• They have a history of recurrent Clostridium difficile infection.
• They have prior history of biologic therapy within the previous 4 years.
• They have received systemic steroids or immunosuppressants within the previous 4 weeks.
• Treatment in the last 14 days that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) or mesalamine enema (Rowasa®).
• Treatment in the last 7 days that included mesalamine (5-ASA) via oral administration (e.g. Asacol®, Lialda®, balsalazide, etc).
• They have a history of cancer (defined as malignancy within 5 years except for squamous cell or basal cell cancers of the skin), asthma, or bronchospasm.
• Positive pregnancy test or lactating subjects.
• There is evidence of chemical substance abuse.
• They have had repeated anti-inflammatory drug treatment (longer than 3 days at doses that exceed those available without a prescription) within the previous 7 days (with exception of aspirin at doses of 325mg/day or less for prophylaxis of cardiac disease), or initiated new non-steroidal anti-inflammatory (NSAID) treatment within the last 30 days.
• They have a known allergy to N-acetylcysteine or mesalamine, or have a history of serious AEs related to their use (including, but not limited to pancreatitis or hepatitis).
• They have a history of failure to retain enemas.
• Other clinically significant diseases that could interfere with the protocol compliance appear. These would include clinically important hematological, renal, hepatic, metabolic, psychiatric, central nervous system (CNS), pulmonary or cardiovascular disease.
• Use of any investigational medication within the previous 90 days.
• Any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome.