Study of the Safety and Tolerability of ALTH12 Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis

Study Overview
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Brief Summary
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This Phase I study will be a closely monitored trial of a small number of subjects to establish, preliminarily, the tolerability and safety of two ALTH12 enema formulations: ALTH12-1:4 and ALTH12-2:4. The study will be conducted in two parts. The first part will be the assessment of the safety and tolerability of a single dose of ALTH12-1:4 or the comparator, mesalamine (4.0g 5-ASA) followed by an assessment of repeated administrations of study drug (ALTH12-1:4 or comparator) for 6 weeks. The second part will be the same assessment for ALTH12-2:4. Three subjects will be enrolled in each cohort: 2 to receive ALTH12 enema therapy and 1 subject to receive comparator enema therapy. A total of up to 9 patients will be enrolled in this study, allowing for up to 3 replacement or additional patients.

Official Title
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A Phase I Double-blind, Randomized, Comparator-controlled Study of the Safety and Tolerability of N-acetylcysteine Plus Mesalamine Enema in Subjects With Left-sided Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: mesalamine
* Drug: ALTH12-1:4
* Drug: ALTH12-2:4


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 active disease or disease in remission. Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI with a sigmoidoscopy score of 1 point or less and Physician's rating of disease score of 1 point or less (mild or remission). Laboratory data: White blood cell count between 4,500 and 10,000 cells/mL Platelet count: 150,000-450,000 cells/mL 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 Amylase < 150 U/L Satisfied one of the following: Female subjects of childbearing potential must have a negative serum 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: Subjects will be excluded if: They have documented history of 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 2 or greater (moderate or severe disease) or an endoscopy score of 2 or greater. They have shown evidence of high grade dysplasia on 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. They have received systemic steroids or immunosuppressants within the previous 4 weeks. Treatment in the last 2 weeks that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) and/or 5-ASA enema (e.g. Rowasa®). 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 abuse. They have a known allergy to N-acetylcysteine or Mesalamine. 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. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Comparator<br>Mesalamine enema | Drug: mesalamine<br>* 4.0g mesalamine rectal suspension, rectally administered enema, 60ml volume, 4.0g mesalamine, once daily<br>* Other names: 5-aminosalicylic acid;|
| Experimental: ALTH12-1:4<br>ALTH12-1:4 experimental treatment dose | Drug: ALTH12-1:4<br>* ALTH12-1:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 1.0g N-acetylcysteine<br>* Other names: enema;|
| Experimental: ALTH12-2:4<br>ALTH12-2:4 experimental treatment dose | Drug: ALTH12-2:4<br>* ALTH12-2:4 rectal suspension, rectally administered enema, 60mL volume, 4.0g mesalamine, 2.0g N-acetylcysteine<br>* Other names: NAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety and tolerability of ALTH12 when given by intrarectal administration over 6 weeks to subjects with ulcerative colitis (UC) involving the left side of the colon |  | 6 weeks treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colitis, inflammatory bowel disease, ulcerative colitis, rectal administration, enema, mesalamine