Clinical trial to evaluate the benefit and safety of ST-0529 in subjects who are suffering from active ulcerative colitis

• Register: EUCTR
• Last refreshed on: 17 May 2021
• Main ID: EUCTR2018-003349-41-HU
• Date of registration: 08/01/2019
• Prospective Registration: Yes
• Primary sponsor: Sublimity Therapeutics (Hold Co) Ltd.
• Public title: Clinical trial to evaluate the benefit and safety of ST-0529 in subjects who are suffering from active ulcerative colitis
• Scientific title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of ST-0529 in Subjects with Moderately to Severely Active Ulcerative Colitis
• Date of first enrolment: 19/02/2019
• Target sample size: 380
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003349-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; 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

Belarus, Belgium, Bulgaria, Canada, France, Germany, Hungary, Ireland, Israel, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Associate Director
• Affiliation: Sublimity Therapeutics

• Name: Associate Director
• Affiliation: Sublimity Therapeutics

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female adult subjects 18 to 75 years old, inclusive.
2. Diagnosis of UC established at least 3 months prior to the Baseline visit, by clinical and endoscopic evidence (colonoscopy or flexible sigmoidoscopy).
3. Moderately to severely active UC defined as the 3-Component Adapted Mayo Score of 5-9, inclusive, with an endoscopic sub-score of = 2 (from central reading), and a rectal bleeding sub-score of = 1, as determined 10 days (± 3 days) prior to Baseline.
4. Evidence of active UC, confirmed histologically (from local read), extending proximal to the rectum with = 15 cm of involved colon.
5. At Screening, a colonoscopy will be required if the subject has had extensive colitis or pancolitis of > 8 years duration or left-sided colitis of > 12 years duration but has not had a colonoscopy within 1 year of the initial screening date. If the subject has had a colonoscopy within 1 year of the initial screening date, a flexible sigmoidoscopy may be
used.
6. Subjects presenting at Screening with moderately to severely active UC demonstrating an inadequate response or loss of response or intolerance/medical contraindication to at least one of the following conventional therapies for UC:
a. Corticosteroids
i. Signs and symptoms of active disease despite treatment with an adequate dose (e.g. prednisolone > 40 mg/day or equivalent) over a period of 4 weeks for oral therapy or IV for up to 1 week or = 9 mg/day oral budesonide;
OR
ii. Unable to reduce corticosteroids below the equivalent of prednisolone 10 mg
daily orally within 3 months of starting steroids or experienced a relapse within 3 months of stopping steroids;
OR
iii. History of, or current intolerance to corticosteroids (including, but not limited to Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection).
b. Immunomodulators
i. Signs and symptoms of active disease despite at least 3 months of treatment with a sufficient dose (oral azathioprine = 1.5 mg/kg or 6-MP = 0.75 mg/kg);
OR
ii. History of, or current dose-limiting toxicity associated with use of the agent (e.g. but not limited to nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection).
c. Anti-TNF agents
i. Signs and symptoms of active disease despite treatment with a single anti-TNF agent. Treatment failure is defined as a relapse after an initial response to therapy as follows:
• Infliximab: At least 4 infusions of at least 5 mg/kg within a 14-week
timeframe for induction and maintenance;
• Adalimumab: Induction regimen incorporating 160 mg at Week 0 (four 40 mg injections in one day or two 40 mg injections per day for two consecutive days) and 80 mg at Week 2, followed by maintenance treatment of 40 mg every other week up to at least Week 8;
• Golimumab: Induction regimen incorporating 200 mg sc injection at Week 0, followed by 100 mg at Week 2 and then maintenance treatment of 50 mg or 100 mg (weight dependent) every 4 weeks after completion of the induction regimen up to at least Week 12;
OR
ii. History of, or current intolerance (with an initial response), defined as the
presence of clinically significant side-effects, including infusion-related hypersensitivity.
d. Vedolizumab
i. Signs and symptoms of active disease despite a history of at least one induction regimen, defined as at least a 14-week (10 weeks in the EU) induction consisting of 300 mg IV at Weeks 0, 2 and 6.
OR
ii. History of intolerance t
Exclusion criteria:
1. Subjects without previous treatment for UC.
2. Ulcerative colitis limited to rectum (ulcerative proctitis).
3. Evidence of acute severe colitis with toxic megacolon, abdominal abscess, bowel stricture or bowel perforation.
4. A diagnosis of Crohn’s colitis, colitis yet to be classified, ischemic colitis, NSAID induced colitis, idiopathic colitis (i.e., colitis not consistent with UC) or radiation colitis.
5. Subjects with evidence of pathogenic bowel infection (Clostridium difficile, Escheria coli, Salmonella, Shigella or Campylobacter).
6. Previous surgery for UC or, in the opinion of the Investigator, will likely require surgery for UC during the study.
7. Any histological evidence of mucosal dysplasia.
8. Any of the following laboratory abnormalities during the screening period – if values are initially outside the prescribed limits, the evaluation may be repeated once within the screening period to determine eligibility:
a. Hemoglobin level < 8.0 g/dL
b. Absolute WBC count < 3.0 × 10^9/L
c. Absolute Lymphocyte count < 0.5 × 10^9/L
d. Absolute neutrophil count < 1.2 × 10^9/L
e. Platelet count < 100 × 10^9/L or >1200 × 10^9/L
f. ALT or AST > 2.5 × ULN
g. Alkaline phosphatase > 2.5 × ULN
h. Serum creatinine > 1.5 × ULN
i. Bilirubin > 1.5 × ULN
9. Treatment with a biologic agent for UC within 56 days or 5 half-lives (whichever is greater) prior to the Baseline visit.
10. Treatment with any calcineurin inhibitor (e.g. cyclosporine or tacrolimus) within 28 days prior to the Baseline visit.
11. Treatment with methotrexate or JAK inhibitors (e.g. tofacitinib) from the initial Screening visit until the end of the study.
12. Initiation of treatment with an oral or IV corticosteroid from the initial Screening visit until the end of the study.




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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Active ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Product Name: ST-0529
Product Code: FP-CYA-050
Pharmaceutical Form: Capsule
INN or Proposed INN: CICLOSPORIN
CAS Number: 59865-13-3
Other descriptive name: cyclosporine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 37.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary efficacy objective is to evaluate the efficacy of ST-0529 in achieving clinical remission in subjects with moderately to severely active ulcerative colitis.

The safety objective is to evaluate the safety and tolerability of treatment with ST-0529 in subjects with moderately to severely active UC.

Secondary Objective: To characterize the pharmacokinetics and pharmacodynamics of ST-0529 in subjects with UC.
To determine the effect of treatment with ST-0529 on health-related Quality of Life in subjects with moderately to severely active UC.

Primary end point(s): The primary efficacy endpoint is clinical remission at Week 12, defined as stool frequency sub-score of = 1 associated with a decrease = 1 point from baseline, rectal bleeding sub-score of 0, and an endoscopic sub-score of = 1 using the 3-Component Adapted Mayo Score.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Secondary end point(s): • Clinical response at Week 12, defined as a decrease from baseline in the 3-Component Adapted Mayo Score of = 2 points and = 30%, with an accompanying decrease in the sub-score for rectal bleeding of = 1 point or an absolute sub-score for rectal bleeding of = 1.
• Endoscopic healing (I) at Week 12 visit defined as an endoscopic sub-score of = 1.
• Corticosteroid-free clinical response at Week 12 in subjects receiving corticosteroids at the Baseline visit.
• Corticosteroid-free clinical remission at Week 12 in subjects receiving corticosteroids at the Baseline visit.
• Changes from baseline in individual Adapted Mayo sub-scores.

Secondary ID(s)

2018-003349-41-DE

CYC-202

Source(s) of Monetary Support

Dr. Falk Pharma GmbH

Sublimity Therapeutics (Hold Co) Ltd.

Ethics review

Status: Approved
Approval date: 19/02/2019
Contact: