A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Symptomatic Ulcerative Colitis Patients with Moderate Disease Activity

Phase 1

• Conditions: Symptomatic Ulcerative Colitis Patients with Moderate to Severe DiseaseActivity; MedDRA version: 19.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2016-000390-20-CZ
• Lead Sponsor: TOPIVERT Pharma Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-18
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Male or female subjects, 18 to 75 years of age, with a documented
diagnosis of UC of at least 3 months duration prior to Screening, based
on medical history, endoscopy, and (if available) histological findings.
Eligible subjects will have a Partial Mayo Clinic Score of 4 to 8,
consisting of all of the following:
• Endoscopy subscore =2 (as per central read)
• Rectal bleeding subscore =1
• Stool frequency subscore =1
• Disease activity extending at least 15 cm proximally from the anal verge
In addition, eligible subjects:
• Will be receiving a stable dose regimen of oral 5-aminosalicylic acid (5-
ASA; =4.8 g/day) for at least 2 weeks prior to the Screening endoscopy,
and be willing to continue the regimen for the duration of the study (required of all subjects in the Czech Republic); or
• If not currently receiving oral 5-ASA, must have received it previously
and experienced a therapeutic failure or intolerance, or have a
contraindication to aminosalicylates (applies to subjects in all
participating countries except the Czech Republic).
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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Receiving any rectally administered medication (i.e., any such
medication, including topical corticosteroids and topical 5-ASA
preparations must have been withdrawn at least 2 weeks prior to
Screening endoscopy).
2. Use of biologic agents (including anti-tumour necrosis factor [TNF]
agents and vedolizumab) within 3 months of Screening endoscopy, or 5
half-lives, whichever is longer.
3. Use of IV corticosteroids within 4 weeks prior to Screening endoscopy.
4. Use of oral corticosteroids at a dose >30 mg/day (or budesonide >9
mg/day).
5. In general, patients who have started receiving immune suppressants
within 3 months of the Screening endoscopy should not be included.
Patients on stable doses of the following medications for 3 months
before the Screening endoscopy will be allowed: azathioprine, 6-
mercaptopurine, or methotrexate.
6. Participated in another study of an investigational medication (or a
medical device) within the last 3 months or 5 half-lives of the
investigational medication, whichever is longer, or is currently
participating in another study of an investigational medication (or a
medical device).
7. Known hypersensitivity to any components of the IMP.
8. At Randomisation, a Partial Mayo Clinic Score of 9 (from the sum of
the endoscopy subscore, rectal bleeding subscore, and stool frequency
subscore)
9. Known or suspected pancolitis (unless on oral 5-ASA, steroids or
permitted immunomodulators as described in the Section 5.8).
10. Known or suspected Crohn's disease, indeterminate colitis,
microscopic colitis, ischaemic colitis, or radiation-induced colitis, based
on medical history, endoscopy, and/or histological findings.
11. Extensive (>50%) colonic resection or colectomy, or prior history of
toxic megacolon within 3 months of Screening.
12. History or presence of colonic mucosal dysplasia. Patients with
dysplasia within a completely resected adenomatous polyp may be
included.
13. Positive history of human immunodeficiency virus, hepatitis B
surface antigen, or hepatitis C.
14. Known history of and/or recent alcohol abuse that, in the opinion of
the Investigator, could influence safety of patient participation in the
study.
15. Any acute or chronic illness (other than UC) affecting the colon
and/or rectum and/or anus
16. Any acute or chronic comorbidity, including cardiovascular, renal,
hepatic, endocrine, pulmonary, or gastrointestinal,
17. Current evidence of or treatment for a malignancy within the past 3
years, other than localised basal-cell or squamous-cell skin cancer,
cervical dysplasia, or carcinoma in situ that has been definitively treated
with standard of care.
18. Patient has active serious infection (e.g., sepsis, pneumonia,
abscess) or has had a serious infection (resulting in hospitalisation or
requiring parenteral antibiotic treatment) within 6 weeks prior to IMP
administration.
19. Patients testing positive for Clostridium difficile toxin or confirmed
with bacterial or parasitical GI infections at Screening. Patients who test
positive for C difficile antigen or who test positive for Blastocystis
hominis may be eligible based on the judgment of the Investigator and
local practice.
20. Patient has received live attenuated vaccination within 6 weeks prior
to Screening or intends to have such a vaccination during the course of
the study.
21. Any of the following haematology values at Screening :
• Absolute neutrophil count <1.0 x 10^9/L (<1000/µL)
• Haemoglobin <8.5 g/dL
• Absolute lymphocyte count <0.

Study & Design

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