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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Double-blind, Randomized, Comparator-controlled Study of the Safety and Efficacy of Zoenasa™ Rectal Gel (Mesalamine Plus N-acetylcysteine) in Subjects With Left-sided Ulcerative Colitis

Conditions
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Ulcerative Colitis, Left-sided Ulcerative Colitis, Distal Ulcerative Colitis

Intervention / Treatment
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* Drug: Zoenasa-1:4
* Drug: Mesalamine Enema


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoenasa-1:4<br> | Drug: Zoenasa-1:4<br>* Zoenasa Rectal Gel (4.0g mesalamine [5-ASA], 1.0g N-acetylcysteine [NAC]; 60ml)<br>|
| Active Comparator: Mesalamine Enema<br> | Drug: Mesalamine Enema<br>* Mesalamine Rectal Suspension Enema (4.0g mesalamine [5-ASA], 60ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in modified UCDAI at 6 weeks | Change from baseline in the modified Ulcerative Colitis Disease Activity Index (modified UCDAI) score at the end of the 6 week treatment period of Zoenasa™ Rectal Gel compared with mesalamine | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in modified UCDAI at 3 weeks | 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 | 3 weeks | 
| Clinical and endoscopic remission rates at 6 weeks | Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline | 6 weeks | 
| Clinical and endoscopic remission rates at 3 weeks | Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline | 3 weeks | 
| Clinical improvement rate after 6 weeks |  | 6 weeks | 
| Clinical improvement rate after 3 weeks |  | 3 weeks | 
| Endoscopic improvement rate at 6 weeks |  | 6 weeks | 
| Endoscopic improvement rate at 3 weeks |  | 3 weeks | 
| Change from baseline in endoscopic appearance after 6 weeks |  | 6 weeks | 
| Change from baseline in endoscopic appearance after 3 weeks |  | 3 weeks | 
| Time to resolution of rectal bleeding |  | Up to 6 weeks | 
| Relapse rates at 6 weeks |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ulcerative colitis, UC, left-sided ulcerative colitis, distal ulcerative colitis, Zoenasa, mesalamine, mesalazine, 5-ASA, 5-aminosalicylic acid, N-acetylcysteine, acetylcysteine, NAC, enema, rectal gel