Distal Ulcerative Colitis, Left-sided Ulcerative Colitis, Ulcerative Colitis
Conditions
Keywords
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
Brief summary
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.
Interventions
DRUGZoenasa-1:4
Zoenasa Rectal Gel (4.0g mesalamine \[5-ASA\], 1.0g N-acetylcysteine \[NAC\]; 60ml)
DRUGMesalamine Enema
Mesalamine Rectal Suspension Enema (4.0g mesalamine \[5-ASA\], 60ml)
Sponsors
Altheus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in modified UCDAI at 6 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and endoscopic remission rates at 6 weeks | 6 weeks | Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline |
| Clinical and endoscopic remission rates at 3 weeks | 3 weeks | Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline |
| Clinical improvement rate after 6 weeks | 6 weeks | — |
| Clinical improvement rate after 3 weeks | 3 weeks | — |
| Endoscopic improvement rate at 6 weeks | 6 weeks | — |
| Change in modified UCDAI at 3 weeks | 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 |
| 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 | — |
| Endoscopic improvement rate at 3 weeks | 3 weeks | — |
Countries
United States
Outcome results
None listed