Clinical trial NCT03521232: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ulcerative Colitis
Ulcerative Proctitis
Ulcerative Proctosigmoiditis
Lead sponsor: Entero Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-05-11
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: 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.
timeFrame: baseline to 6 weeks
Secondary outcomes:
measure: Number of subjects with clinical remission defined as MMS* ≤ 2 with no individual subscore >1 after 6 weeks of treatment
timeFrame: baseline to 6 weeks
Other outcomes:
measure: Change in signs and symptoms (rectal bleeding and stool frequency) from baseline to 2, 4 and 6 weeks of treatment
timeFrame: from baseline to 2, 4 and 6 weeks
measure: Change in sigmoidoscopic score (mucosal appearance) from baseline to 6 weeks of treatment
timeFrame: baseline to 6 weeks
measure: Change in hs-CRP and fecal calprotectin from baseline to 2, 4 and 6 weeks of treatment
timeFrame: baseline to 2, 4 and 6 weeks
measure: Change in histology (Geboes index) from baseline to 6 weeks of treatment
timeFrame: baseline to 6 weeks
measure: Change in safety laboratory tests from baseline to 6 weeks of treatment
timeFrame: baseline to 6 weeks
measure: Change in 12-lead ECG parameters from baseline to 2, 4 and 6 weeks of treatment
timeFrame: baseline to 2, 4 and 6 weeks of treatment
measure: Change in heart rate from baseline to 2, 4 and 6 weeks of treatment
timeFrame: baseline to 2, 4 and 6 weeks
measure: Change in quality of life (12-item Short-Form) from baseline to 6 weeks of treatment
timeFrame: baseline to 6 weeks
measure: Plasma levels of niclosamide measured before and after dosing
timeFrame: baseline to 6 weeks
measure: Change in sitting systolic and diastolic blood pressure from baseline to 2, 4 and 6 weeks of treatment
timeFrame: baseline to 2, 4 and 6 weeks
measure: Change in body temperature from baseline to 2, 4 and 6 weeks of treatment
timeFrame: baseline to 2, 4 and 6 weeks
Locations:
city: Rome
country: Italy
facility: Tor Vegata
Study officials:
affiliation: First Wave BioPharma
name: James Pennington, M.D.
role: STUDY_DIRECTOR
References: