Phase I/IIa, 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

Phase 1

• Conditions: lcerative Proctitis (UP) or Ulcerative Procto-Sigmoiditis (UPS); MedDRA version: 20.0Level: PTClassification code 10036783Term: Proctitis ulcerativeSystem Organ Class: 10017947 - Gastrointestinal disorders; MedDRA version: 20.0Level: LLTClassification code 10036789Term: ProctosigmoiditisSystem Organ Class: 10017947 - Gastrointestinal disorders; MedDRA version: 20.1Level: LLTClassification code 10045362Term: Ulcerative (chronic) proctosigmoiditisSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2017-000319-18-AT
• Lead Sponsor: First Wave BioPharma, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-19
• Last Update Posted: 16 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

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 UC (subcategories UP and /or UPS) with a duration of at least 3 months prior to the Screening Visit, extending at least 5 cm, but no further 40 cm from the anal verge. Patients who at the time of screening endoscopy have active disease identified in the sigmoid colon without active disease being apparent in the rectum as result of recent topical treatment within 2 weeks from screening are eligible.
5. MMS score =4 to < 8 (range: 0-9) prior to enrolment in the study, with verification of the following conditions:
• Stool frequency subscore (SFS) = 1
• Rectal bleeding subscore (RBS) = 1 or 2;
• Endoscopic sub-score (mucosal appearance) = 1 or 2;
6. Availability to perform an endoscopy (colonoscopy or flexible rectosigmoidoscopy); colonoscopy is mandatory only if not been performed within 12 months prior to the Screening Visit; For the patient that will not go through the colonoscopy procedure, an abbreviated endoscopic procedure to collect the biopsy will be performed.
7. Patients who have relapsed on maintenance therapy with oral and/or rectal doses of 5-ASA;
8. Patients must meet the following laboratory criteria:
• White blood cells (WBC) count =3000/mm3 (=3.0 × 10^9/L) and <14,000/mm3 (<14 × 10^9/L);
• Platelet count =100,000/mm3 (=100 × 10^9/L);
• Serum creatinine =1.5 mg/dL (=132.6 µmol/L);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2 × upper limit of normal (ULN). If initial test shows ALT or AST >2 × ULN, one repeated test is allowed during the screening period;
• Total bilirubin =2 mg/dL (= 34 µmol/L) or albumin > LLN (lower limit of normal). If initial total bilirubin test result is >2 g/dL, one repeated test is allowed during the screening period;
• Hemoglobin = 9 g/dL (=5.6 mmol/L);
9. Females of childbearing potential (FCBP) must have a negative pregnancy test at screening and the Baseline Visit. While receiving the investigational medicinal product (IMP) and for at least 28 days after taking the last dose of IMP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
• Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy;
OR
• Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]; PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide;
10.Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while receiving the IMP and for at least 28 days after taking the last dose of IMP.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3

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. Patients 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. Evidence of pathogenic enteric infection;
5. History of colorectal cancer or colorectal dysplasia;
6. Use of any tumor necrosis factor (TNF) inhibitors (or any biologic agent) within 12 months prior to screening;
7. Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine, or thalidomide;
8. Patients who in the opinion of the Investigator may require treatment with chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and / or aspirin during the entire study (may potentially require daily or more frequent dosing for continuous periods longer than 7 days);
9. Use of budesonide-multimatrix (MMx) within the last 8 weeks of day 1 (first study treatment);
10. Use of oral and/or IV corticosteroids within the last 2 weeks of day 1 (first study treatment);
11. Use of immunosuppressants (azathioprene [AZA], 6-mercaptopurine [6-MP] or methotrexate [MTX]) within the last 8 weeks of day 1 (first study treatment);
12. Current use of coumadin, unfractionated or low molecular weight heparins or anticoagulant medications other than aspirin due to bleeding risk;
13.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;
14.History of any of the following cardiac conditions within 6 months of screening: myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery, interventional cardiac catheterization (with or without a stent placement), interventional electrophysiology procedure, or presence of implanted defibrillator;
15.History of suicide attempt at any time in the subject’s lifetime prior to study start or major psychiatric illness requiring hospitalization within 3 years before study start;
16. 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;
17. Pregnant or breast feeding females;
18. 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;
19. Patients with active hepatitis B, C and HIV infections;
20. Patients with active intestinal parasite infections;
21. History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease);
22. History of malignancy, except for:
• Treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
• Treated (ie, cured) carcinoma in situ of the cervix with no evidence of recurrence within th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified