English 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 to Severe Disease Activity

• Register: EUCTR
• Last refreshed on: 12 March 2018
• Main ID: EUCTR2016-000390-20-PL
• Date of registration: 16/06/2016
• Prospective Registration: Yes
• Primary sponsor: TOPIVERT Pharma Limited
• Public title: English 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 to Severe Disease Activity
• Scientific title: 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 to Severe Disease Activity
• Date of first enrolment: 28/06/2016
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000390-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Hungary, Latvia, Lithuania, Poland, Ukraine, United Kingdom

Contacts

• Name: Head of Clinical Development
• Affiliation: TOPIVERT Pharma Limited

• Name: Head of Clinical Development
• Affiliation: TOPIVERT Pharma Limited

Key inclusion & exclusion criteria

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 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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-tumor 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 109/L (<1000/µL), Haemoglobin <8.5 g/dL, Absolute ly

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Symptomatic Ulcerative Colitis Patients with Moderate to Severe Disease Activity
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: TOP1288 Rectal solution
Pharmaceutical Form: Rectal solution
INN or Proposed INN: Not Applied for
CAS Number: 1630202-02-6
Current Sponsor code: TOP1288
Other descriptive name: TOP1288 rectal solution
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Rectal solution
Route of administration of the placebo: Rectal use

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are to assess the effect of TOP1288 200 mg Rectal Solution on the following:
• Assessment of safety, including AEs, vital signs, ECG, and laboratory test results (i.e., clinical chemistry, haematology, and urinalysis)
• Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score
• Partial Mayo Clinic score (i.e., the sum of the endoscopic, rectal bleeding, and stool frequency subscores)
• Endoscopic healing (indicated by the Mayo Clinic modified endoscopic subscore)
• Rectal bleeding (indicated by the Mayo Clinic rectal bleeding subscore)

Timepoint(s) of evaluation of this end point: at Week 4

Main Objective: The primary objective of the study is to assess the effect of TOP1288 200 mg Rectal Solution on endoscopic remission, as indicated by the Mayo Clinic modified endoscopic subscore, after 4 consecutive weeks of daily bedtime treatment

Primary end point(s): Primary Efficacy Endpoint:
• Proportion of subjects achieving endoscopic remission (defined as a Mayo Clinic modified endoscopy subscore of 0 or 1) at Week 4

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Change from Baseline to Week 4

Secondary end point(s): Secondary Efficacy Endpoint(s):
Change from Baseline to Week 4 in:
• UCEIS score
• Partial Mayo Clinic score (the sum of endoscopic, rectal bleeding, and stool frequency subscores)
• Proportion of subjects with endoscopic healing (defined as a Mayo Clinic modified endoscopic subscore of 0)
• Proportion of subjects with an improvement in Mayo Clinic rectal bleeding subscore of =1

Secondary ID(s)

TOP1288-TV-02

2016-000390-20-GB

Source(s) of Monetary Support

TOPIVERT Pharma Limited