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.

Tracking Information

• First Submitted Date: April 17, 2018
• First Posted Date: May 11, 2018
• Last Update Posted Date: September 7, 2020
• Actual Study Start Date: May 15, 2018
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2018)

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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 9, 2018): 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 ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 9, 2018)

• 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 ]
• Change in sigmoidoscopic score (mucosal appearance) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• 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 ]
• Change in histology (Geboes index) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• 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
• 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
• 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
• Change in quality of life (12-item Short-Form) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• Plasma levels of niclosamide measured before and after dosing [ Time Frame: baseline to 6 weeks ]
• 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
• 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

Original Other Pre-specified Outcome Measures (submitted: May 9, 2018)

• 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 ]
• Change in sigmoidoscopic score (mucosal appearance) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• 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 ]
• Change in histology (Geboes index) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• 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
• Change in 12-lead ECG from baseline to 2, 4 and 6 weeks of treatment [ Time Frame: baseline to 2, 4 and 6 weeks of treatment ]
• 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
• Change in quality of life (12-item Short-Form) from baseline to 6 weeks of treatment [ Time Frame: baseline to 6 weeks ]
• Plasma levels of niclosamide measured before and after dosing [ Time Frame: baseline to 6 weeks ]
• Change in 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
• 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

Descriptive Information

• Brief Title: A Study of Niclosamide Enemas in Subjects With Active Ulcerative Proctitis or Ulcerative Proctosigmoiditis
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

• Ulcerative Colitis
• Ulcerative Proctitis
• Ulcerative Proctosigmoiditis

Intervention

Drug: Niclosamide

enema given twice daily for 6 weeks

Study Arms

• Experimental: 150 mg/60 ml
  Niclosamide enemas 150 mg/60 ml given twice daily for 6 weeks
  Intervention: Drug: Niclosamide
• Experimental: 450 mg/60 ml
  Niclosamide enemas 450 mg/60 ml given twice daily for 6 weeks
  Intervention: Drug: Niclosamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 9, 2018): 51
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT03521232
• Other Study ID Numbers: FW-UC-2017
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: First Wave Bio, Inc.
• Study Sponsor: First Wave Bio, Inc.
• Collaborators: Not Provided

Investigators

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

• PRS Account: First Wave Bio, Inc.
• Verification Date: September 2020