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

• ClinicalTrials.gov Identifier: NCT03521232
• Recruitment Status: Recruiting
• First Posted: May 11, 2018
• Last Update Posted: September 7, 2020
• Sponsor: First Wave Bio, Inc.
• Information provided by (Responsible Party): First Wave Bio, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis; Ulcerative Proctitis; Ulcerative Proctosigmoiditis	Drug: Niclosamide	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 51 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: May 15, 2018
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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. [ Time Frame: baseline to 6 weeks ]
   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.

Secondary Outcome Measures :

1. Number of subjects with clinical remission defined as MMS* ≤ 2 with no individual subscore >1 after 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Giovanni MONTELEONE, M.D.; 39 0620900969; gi.monteleone@med.uniroma2.it

Locations

Italy

Fondazione IRCCS Policlinico San Matteo - Phase I Clinical Trial Unit And Experimental Therapy; Recruiting

Pavia, Italy

Contact: Antonio Disabatino

U.O.C. Gastroenterologia ed Endoscopia Digestiva - Azienda Ospedaliera Universitaria PTV - Policlinico; Suspended

Roma, Italy

Centro Ricerche Cliniche di Verona; Recruiting

Verona, Italy

Contact: Rachele Ciccocioppo, M.D.

Sponsors and Collaborators

First Wave Bio, Inc.

Investigators

• Principal Investigator: Giovanni MONTELEONE; U.O.C. Gastroenterologia ed Endoscopia Digestiva - Azienda Ospedaliera Universitaria PTV - Policlinico

More Information

• Responsible Party: First Wave Bio, Inc.
• ClinicalTrials.gov Identifier: NCT03521232
• Other Study ID Numbers: FW-UC-2017
• First Posted: May 11, 2018
• Last Update Posted: September 7, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Colitis, Ulcerative; Proctitis; Proctocolitis; Ulcer; Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases; Rectal Diseases; Sigmoid Diseases; Niclosamide; Anticestodal Agents; Antiplatyhelmintic Agents; Anthelmintics; Antiparasitic Agents; Anti-Infective Agents; Antinematodal Agents