A Study of Niclosamide Enemas in Subjects With Active Ulcerative Proctitis or Ulcerative Proctosigmoiditis

Study Overview
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Brief Summary
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This will be a phase I/IIa, open-label, three-stage, single center study aimed at investigating the safety, the efficacy (clinical and endoscopic effects) and the pharmacokinetics of Niclosamide enema 150 mg/60 ml and 450 mg/60 ml in subjects with mild-to-moderate UP and UPS, defined as a Modified Mayo Score (MMS) ≥ 4 and < 8, with a stool frequency subscore (SFS) ≥ 1, a rectal bleeding sub-score (RBS) = 1 or 2, and an endoscopic subscore (mucosal appearance) = 1 or 2. At the endoscopic sub-score any degree of friability will be classified as having a sub-scale score of 2.

Official Title
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A Phase I/IIA, Open-Label, Three-Stage Study to Investigate the Safety, the Efficacy and the Pharmacokinetics of Niclosamide Enemas in Subjects With Active Ulcerative Proctitis or Ulcerative Procto-Sigmoiditis

Conditions
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Ulcerative Colitis, Ulcerative Proctitis, Ulcerative Proctosigmoiditis

Intervention / Treatment
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* Drug: Niclosamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged ≥ 18 years at the time of signing the informed consent; Must understand and voluntarily sign an informed consent from (ICF) prior to any study-related assessments/procedures being conducted. Must be able to adhere to the study visit schedule and other protocol requirements; Diagnosis of UP or UPS with a duration of at least 3 months prior to the Screening Visit MMS score ≥4 to < 8 (range: 0-9) prior to enrolment in the study. Availability to perform an endoscopy (colonoscopy or flexible rectosigmoidoscopy); Exclusion Criteria: Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis, or diverticular disease-associated colitis; UC extended more than 40 cm from the anal verge; Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study; History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, psychiatric, endocrine, hematological disorder or disease or any other medical condition that, in the Investigator's opinion, would preclude participation in the study; Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study; Pregnant or breast feeding females; Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis, atypical mycobacterial disease, and herpes zoster), human immunodeficiency virus (HIV), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) or oral antibiotics within 4 weeks of screening; Subjects who have received any investigational drug or device in the last 3 months; History of alcohol, drug, or chemical abuse within the last 6 months; Known hypersensitivity to niclosamide or any excipients in the formulation.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150 mg/60 ml<br>Niclosamide enemas 150 mg/60 ml given twice daily for 6 weeks | Drug: Niclosamide<br>* enema given twice daily for 6 weeks<br>|
| Experimental: 450 mg/60 ml<br>Niclosamide enemas 450 mg/60 ml given twice daily for 6 weeks | Drug: Niclosamide<br>* enema given twice daily for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of Niclosamide enemas 150 mg/60 ml and 450 mg/60 ml graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Number of subjects with serious adverse reactions (i.e. treatment-related) during 6 weeks of treatment with Niclosamide enemas; Number of subjects with grade ≥ 3 adverse reactions during 6 weeks of treatment with Niclosamide enemas; Number of subjects with grade ≥ 2 adverse reactions during 6 weeks of treatment with Niclosamide enemas. | baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with clinical remission defined as MMS* ≤ 2 with no individual subscore >1 after 6 weeks of treatment |  | baseline to 6 weeks |