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

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

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.

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis; Ulcerative Proctitis; Ulcerative Proctosigmoiditis
• Intervention / Treatment: Drug: Niclosamide

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy
    • Tor Vegata

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years at the time of signing the informed consent;
2. Must understand and voluntarily sign an informed consent from (ICF) prior to any study-related assessments/procedures being conducted.
3. Must be able to adhere to the study visit schedule and other protocol requirements;
4. Diagnosis of UP or UPS with a duration of at least 3 months prior to the Screening Visit
5. MMS score ≥4 to < 8 (range: 0-9) prior to enrolment in the study.
6. Availability to perform an endoscopy (colonoscopy or flexible rectosigmoidoscopy);

Exclusion Criteria:

1. Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis, or diverticular disease-associated colitis;
2. UC extended more than 40 cm from the anal verge;
3. 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;
4. 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;
5. 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;
6. Pregnant or breast feeding females;
7. 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;
8. Subjects who have received any investigational drug or device in the last 3 months;
9. History of alcohol, drug, or chemical abuse within the last 6 months;
10. Known hypersensitivity to niclosamide or any excipients in the formulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150 mg/60 ml; Niclosamide enemas 150 mg/60 ml given twice daily for 6 weeks	Drug: Niclosamide; enema given twice daily for 6 weeks
Experimental: 450 mg/60 ml; Niclosamide enemas 450 mg/60 ml given twice daily for 6 weeks	Drug: Niclosamide; enema given twice daily for 6 weeks

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in signs and symptoms (rectal bleeding and stool frequency) from baseline to 2, 4 and 6 weeks of treatment		from baseline to 2, 4 and 6 weeks
Change in sigmoidoscopic score (mucosal appearance) from baseline to 6 weeks of treatment		baseline to 6 weeks
Change in hs-CRP and fecal calprotectin from baseline to 2, 4 and 6 weeks of treatment		baseline to 2, 4 and 6 weeks
Change in histology (Geboes index) from baseline to 6 weeks of treatment		baseline to 6 weeks
Change in safety laboratory tests from baseline to 6 weeks of treatment	the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided	baseline to 6 weeks
Change in 12-lead ECG parameters from baseline to 2, 4 and 6 weeks of treatment	1. PR interval 2. RR interval 3. QRS interval 4 QT interval 5. HR interval 6. QtcF interval. All intervals summarized descriptively by visit	baseline to 2, 4 and 6 weeks of treatment
Change in heart rate from baseline to 2, 4 and 6 weeks of treatment	summarized descriptively by visit and presented as shift tables	baseline to 2, 4 and 6 weeks
Change in quality of life (12-item Short-Form) from baseline to 6 weeks of treatment		baseline to 6 weeks
Plasma levels of niclosamide measured before and after dosing		baseline to 6 weeks
Change in sitting systolic and diastolic blood pressure from baseline to 2, 4 and 6 weeks of treatment	summarized descriptively by visit and presented as shift tables	baseline to 2, 4 and 6 weeks
Change in body temperature from baseline to 2, 4 and 6 weeks of treatment	summarized descriptively by visit and presented as shift tables	baseline to 2, 4 and 6 weeks

Collaborators and Investigators

• Sponsor: First Wave Bio, Inc.
• Investigators: Study Director: James Pennington, M.D., First Wave BioPharma

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): September 19, 2022
• Study Completion (Actual): October 4, 2022

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Inflammatory Bowel Diseases; Colitis; Sigmoid Diseases; Ulcer; Colitis, Ulcerative; Proctitis; Proctocolitis; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: FW-UC-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No