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

NCT03521232 | Terminated Phase 1 DMC

• 1 other identifier: FW-UC-2017
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis; Ulcerative Proctitis; Ulcerative Proctosigmoiditis

Outcome Measures

Primary Outcomes (1)

• 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.

  1. Number of subjects with serious adverse reactions (i.e. treatment-related) during 6 weeks of treatment with Niclosamide enemas; 2. Number of subjects with grade ≥ 3 adverse reactions during 6 weeks of treatment with Niclosamide enemas; 3. Number of subjects with grade ≥ 2 adverse reactions during 6 weeks of treatment with Niclosamide enemas.

  baseline to 6 weeks

Secondary Outcomes (1)

• 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 Outcomes (11)

• 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

Study Arms (2)

150 mg/60 ml

EXPERIMENTAL

Niclosamide enemas 150 mg/60 ml given twice daily for 6 weeks

Drug: Niclosamide

450 mg/60 ml

EXPERIMENTAL

Niclosamide enemas 450 mg/60 ml given twice daily for 6 weeks

Drug: Niclosamide

Interventions

Niclosamide DRUG

enema given twice daily for 6 weeks

150 mg/60 ml; 450 mg/60 ml

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• Entero Therapeutics: lead

Study Sites (1)

Tor Vegata

Rome, Italy

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Niclosamide

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Officials

• James Pennington, M.D.

  First Wave BioPharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 11, 2018
• Study Start: May 15, 2018
• Primary Completion: September 19, 2022
• Study Completion: October 4, 2022
• Last Updated: November 29, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)