E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic Ulcerative Colitis Patients with Moderate to Severe Disease Activity |
|
E.1.1.1 | Medical condition in easily understood language |
Symptomatic Ulcerative Colitis Patients |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
|
E.2.2 | Secondary objectives of the trial |
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) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). |
|
E.4 | Principal 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 no 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 judgement 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 <0.5 x 10^9/L (<500/μL)
22. Renal or liver impairment, defined as any of the following (although
borderline cases crossing these thresholds may be eligible following
discussion with the QuintilesIMS medical monitor):
• Serum creatinine level ≥1.5 x upper limit of normal (ULN)
• ALT, AST or alkaline phosphatase ≥3 x ULN
• Total bilirubin >1.5 x ULN |
|
E.5 End points |
E.5.1 | 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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | 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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from Baseline to Week 4 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
Hungary |
Latvia |
Lithuania |
Poland |
Ukraine |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The last enrolled subject’s phone call or optional site visit during the safety follow-up period will mark the end of the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |