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

Phase 2

• Conditions: Left-sided Ulcerative Colitis; Ulcerative Colitis; Distal Ulcerative Colitis
• Interventions: Drug: Mesalamine Enema

• Registration Number: NCT01586533
• Lead Sponsor: Altheus Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-04-25
• Study First Submitted QC: 2012-04-26
• Study First Posted: 2012-04-27
• Study Start: 2012-06
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-07
• Last Update Posted: 2014-01-08
• Primary Completion: 2014-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mesalamine Enema	Mesalamine Enema	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Time to resolution of rectal bleeding	Up to 6 weeks
Clinical and endoscopic remission rates at 6 weeks	6 weeks	Proportion of patients in clinical and endoscopic remission at 6 weeks compared to baseline
Endoscopic improvement rate at 3 weeks	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
Change from baseline in endoscopic appearance after 6 weeks	6 weeks
Change from baseline in endoscopic appearance after 3 weeks	3 weeks
Relapse rates 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
Clinical and endoscopic remission rates at 3 weeks	3 weeks	Proportion of patients in clinical and endoscopic remission at 3 weeks compared to baseline

Trial Locations

Locations (45)

Birmingham Gastroenterology Associates; 🇺🇸 Birmingham, Alabama, United States

Digestive Health Specialists of the Southeast; 🇺🇸 Dothan, Alabama, United States

Rocky Mountain Gastroenterology; 🇺🇸 Lakewood, Colorado, United States

Digestive Disease Associates; 🇺🇸 Gainesville, Florida, United States

Digestive Medical Associates; 🇺🇸 Hialeah, Florida, United States

The Center for Gastrointestinal Disorders; 🇺🇸 Hollywood, Florida, United States

Miami Gastroenterology Consultants P.A.; 🇺🇸 Miami, Florida, United States

South Medical Research Group; 🇺🇸 Miami, Florida, United States

Gastroenterology of Naples; 🇺🇸 Naples, Florida, United States

Advanced Gastroenterology Associates; 🇺🇸 Palm Harbor, Florida, United States

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