Ulcerative Colitis, Ulcerative Proctitis, Ulcerative Proctosigmoiditis
Conditions
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.
Interventions
DRUGNiclosamide
enema given twice daily for 6 weeks
Sponsors
Entero Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 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 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 | 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 | baseline to 2, 4 and 6 weeks | summarized descriptively by visit and presented as shift tables |
| Change in heart rate from baseline to 2, 4 and 6 weeks of treatment | baseline to 2, 4 and 6 weeks | summarized descriptively by visit and presented as shift tables |
| Change in sigmoidoscopic score (mucosal appearance) from baseline to 6 weeks of treatment | baseline to 6 weeks | — |
Countries
Italy
Outcome results
None listed